2025_Scientific_Report_Single_Pages_Digital

St. Jude researchers, backed by extraordinary resources and support teams, are focused on making big discoveries.

Scientific Highlights

Discovering a molecular driver of lethal outcomes for viral respiratory disease

Improving long-term academic achievement through early interventions 52

A breakthrough in battling resistance with next-generation antibiotics 53 A blueprint for translating genome-editing strategies to clinical trials 54

Characterizing approaches to treatment decision-making for children presenting with advanced cancer in resource-limited settings 55

Solving the decades-long mystery of NLRC5 sensor function in inflammation and disease 56

Epigenetic insights help reveal the causes of unsolved epileptic neurological disorders 57

Discoveries are ‘one click’ away with the St. Jude survivorship portal 58

‘Molecular putty’ properties of biomolecular condensates coded in protein sequence 59

Scientists combine novel CAR design and AI to improve CAR T–cell immunotherapy 60

Switching gears in glutamine metabolism is key to red blood cell development and disease 61

Behind the Cover

Light is a powerful force that fuels, illuminating discoveries and transforming our understanding of biological processes, molecular dynamics, human health, and disease. Modern microscopes and imaging techniques allow St. Jude researchers to manipulate light and energy to visualize aspects of science that can be leveraged to create novel treatments for catastrophic diseases. At the heart of fluorescence microscopy is the filter cube, which controls the path of light. The filter cube facilitates sample excitation and fluorescence signal detection, illuminating the target molecule(s). This artistic rendering of light at a specific wavelength passing through a filter cube to excite fluorophores embodies the concept of “lighting the way to knowledge.” The cube, sitting amidst a stream of computational data, represents how this technology integrates within a suite of scientific methods to generate impactful science. Artwork by Leena Xaypanya

Privileged communication. Copyright © 2025 St. Jude Children’s Research Hospital. No part of this communication may be cited, reproduced, stored in a retrieval system, or transmitted by electronic or other means without prior written permission of the President and CEO and the appropriate investigator.

This report reflects the activities of St. Jude Children’s Research Hospital during 2024.

PIONEERS OF CHANGE PAVE THE FUTURE

When Danny Thomas founded St. Jude Children’s Research Hospital in 1962, he envisioned a place where science and medicine could work together to achieve the extraordinary — to ensure that no child dies in the dawn of life from a catastrophic disease. That vision continues to guide us today as we generate knowledge to transform the outlook for children with cancer and other life-threatening illnesses, not only in the United States but around the world.

Since we opened our doors more than six decades ago, St. Jude has made remarkable progress in curing the incurable, treating the untreatable, and improving the quality of life for patients and survivors. Yet, significant challenges remain. At St. Jude, we are uniquely positioned to address these challenges, leveraging unparalleled talent and resources to push the boundaries of science and medicine. We are committed to building systems that ensure the cures we develop reach children everywhere.

The Scientific Report 2025 celebrates the advancements made by St. Jude faculty and staff over the past year. These achievements reflect the institution’s unique scientific culture — one that encourages bold ideas and collaboration to tackle the hardest problems and answer the toughest questions. By combining fundamental biological research with extensive clinical expertise, we generate knowledge that drives transformative discoveries and changes the way medicine is practiced.

This year’s report showcases groundbreaking advancements across disciplines, from precision genomics transforming pediatric leukemia care to predictive medicine reducing symptom burdens, from immunotherapy innovations enhancing T-cell functionality to improving outcomes for survivors and at-risk children. In fundamental biology, cutting-edge tools are revealing new mechanisms of cellular communication and molecular interactions, reshaping

our understanding of complex systems. St. Jude is also accelerating progress through intelligent solutions, including the launch of the Office of Data Science and the integration of advanced technologies for translational impact. Together, these achievements reflect our commitment to generating knowledge that improves outcomes and ensures cures reach children worldwide.

As we reflect on the progress of the past year, we celebrate the dedication, talent, and collaboration that make these achievements possible. Together, we continue to honor Danny Thomas’s vision by transforming hope into reality for children with catastrophic diseases.

James R. Downing, MD President and Chief Executive Officer

St. Jude Children’s Research Hospital

Total internal reflection fluorescence (TIRF) microscopy is a powerful imaging technique that relies on a prism to direct light into the chamber in such a way that only the sample is illuminated — a concept called optical sectioning.

Scientists

are knowledge hunters who seek an objective understanding of the world.

Acquiring this understanding relies on the tools a scientist has in their toolkit. Light is a critical tool. It illuminates the material world and can reveal what is hidden by darkness. St. Jude researchers work on the cutting edge of science, often butting up against physical boundaries that limit the types of biological questions they can answer. However, researchers have shown that they can push past the boundaries of what has been possible, creating new approaches to peer into the unknown. The resulting discoveries illuminate science, lighting the way to knowledge.

Go ahead, FRET the small stuff

Fluorophores are molecules that can absorb visible light, which in turn enables electrons to jump to higher energy states. Upon relaxation of the electron, that energy is sometimes released as glowing light (fluorescence). Combining fluorescence with microscopy is a powerhouse pairing that can detect cellular structures and biological processes, which can inform foundational biology and the diagnosis and treatment of human diseases.

Biomolecules change their shape, or conformation, to interact with binding

partners and complete physiological functions. These movements can be subtle and localized — occurring on a time scale around one quadrillionth of a second — or more exaggerated, on a time scale of microseconds to seconds. Understanding how biomolecules move while they work is key to understanding their function.

Technological advances in microscope mechanics, improved data processing, and reimagined fluorophores have increased the speed and precision of fluorescence microscopy. Scientists can now study the movements of individual molecules in real time by using singlemolecule Förster resonance energy transfer (smFRET). This method works by placing two or more fluorophores on different parts of a molecule, exciting the sample with light, and measuring the energetic communication among the fluorophores. Quantifying the energy transfer between fluorophores informs scientists about the distance between them, which can be on the scale of one-billionth of an inch. This level of sensitivity makes this technique ideal for measuring biological processes at the molecular scale.

One limitation of fluorescence-based imaging methods is that fluorophores can fail to fluoresce because of a change in a fundamental property of the excited electron called its spin state. “Every time an electron is excited, there’s a probability that it will lose memory of its spin and adopt an inverted spin state,” said Scott Blanchard, PhD, Department of Structural Biology. “If this occurs, it cannot relax back to its ground state and becomes trapped in a highly reactive, nonfluorescent triplet state that is 100,000 times longer-lived.”

Triplet states, called “dark states,” impact a fluorophore’s brightness and durability and cause phototoxicity. Dark states also reduce data quality and accuracy.

choice but to try to find solutions.”

The need to succeed led Blanchard’s team to intramolecularly tether triplet state quenchers to fluorophores. This discovery gave researchers a generalizable strategy to reduce dark state lifetimes in fluorophores by as much as 1000fold. Fluorophores imbued with this property are called “self-healing.”

Published in Nature Methods, this study by Blanchard’s team demonstrated for the first time that self-healing fluorophores enable more robust and precise molecular-scale measurements. This transformative work substantially advances smFRET imaging and helps ascertain the function of biological molecules. However, the self-healing technology has the potential to benefit all forms of fluorescence imaging, which

What the field believed was that triplet states were an immutable reality. But we had no other choice but to try to find solutions.

Scott Blanchard, PhD Department of Structural Biology

Blanchard hopes will be advantageous to fluorescence microscopy pursuits at St. Jude and around the world.

Necessity is the mother of invention, and Lindsay Schwarz, PhD, Department of Developmental Neurobiology, agrees with that ancient Greek proverb. Schwarz researches norepinephrineexpressing (NE) neurons, which represent about 0.00003% of brain cells. These cells modulate anxiety, attention, memory, and stress responses.

Aberrant responses by NE neurons can cause mental health issues, including anxiety and depression. “We treat anxiety and depression with drugs that target norepinephrine signaling, but these drugs act globally, meaning there’s often a detriment to other important functions for norepinephrine that you don’t want to see,” explained Schwarz. “Targeting these neurons more specifically could help ameliorate that.”

A postdoctoral researcher uses fluorescence microscopy to study cellular diversity.

subpopulations expressing overlapping elements or genetic features, a userfriendly intersectional approach — something that did not exist.

Writing in Nature Neuroscience, Schwarz and former St. Jude graduate student Alex Hughes, PhD, detailed the development of Conditional Viral Expression by RibozymeGuided Degradation (ConVERGD).

ConVERGD is an intersectional expression platform pairing adenoassociated virus vectors, which insert genetic material called transgenes, with ribozymes (RNA strands that catalyze reactions) to express desired traits in specific cellular subsets.

ConVERGD constructs activate transgenes and fluoresce only when two protein recombinases, Flp and Cre, are present.

the transcribed mRNA and prevent protein production. Flp and Cre can be introduced into many cells and organisms and can be activated independently through functional programs that are distinct to specific cells. Utilizing these molecular elements in the way that ConVERGD does allows specificity in identifying cell lineages and subsets in living organisms based on multiple parameters, highlighting the versatility of this approach. ConVERGD can also be used in other systems beyond the brain.

As proof of concept, Schwarz’s team looked for NE neurons that also expressed prodynorphin (Pdyn), which was thought to be involved in anxiety. Using ConVERGD, the researchers fluorescently labeled a targeted subpopulation of neurons expressing both Pdyn and Dbh, which makes

These methods are now being used by other labs to study important processes in the brain in ways that haven’t been done before.

Lindsay Schwarz, PhD Department of Developmental Neurobiology

A St. Jude scientist prepares tissue samples for scanning electron microscopy.

ConVERGD-based viral tools made it possible for Schwarz’s team to identify the anatomical connectivity and behavioral influence of Pdyn+/ Dbh+ NE neurons and helped the field understand how this unique population of neurons provokes such diverse behavioral states — a question that has fascinated researchers for years.

Schwarz continues to expand the ConVERGD toolkit. She said, “These methods are now being used by other labs to study important processes in the brain in ways that haven’t been done before.”

Seeing is believing

How researchers experimentally use illumination varies as technology advances. This is the case in the laboratory of Stacey Ogden, PhD, Department of Cell & Molecular Biology, who studies the role of signaling molecules such as Sonic Hedgehog (SHH).

Precisely when and where a cell receives an SHH signal is tightly regulated during development to ensure tissues and organs pattern properly. Still, scientists were unclear about how SHH reaches target cells with appropriate precision.

For a long time, visualizing these structures in complex developing mammalian tissue has been challenging, but we’ve finally found a way.

Stacey Ogden, PhD Department of Cell & Molecular Biology

Some wondered if thread-like cellular projections called cytonemes were involved, but no one had visualized the structures in mammalian tissue — not until Ogden reevaluated the capabilities of imaging science and, quite literally, saw cytonemes in a new light.

“For a long time, visualizing these structures in complex developing mammalian tissue has been challenging,” Ogden said. “But we’ve finally found a way.”

In Cell, Ogden described combining modern microscopy with optimized sample preparation to see fluorescent thread-like protrusions extending from cells. Ogden’s team systematically tested various methods of sample preparation, fixation, and imaging to ascertain the most conducive protocols for imaging in mammalian tissue.

To effectively visualize the cellular membrane extensions, the team leveraged a genetic lineage tracer in which membranes of SHH-expressing cells are labeled with a fluorescent protein. To preserve the 3D structure, tissues expressing the fluorescent marker were sectioned with a device called a vibratome, which allowed the researchers to create tissue sections that were thick enough to preserve cytonemes but thin enough to facilitate imaging of the membrane marker. Sectioning with the vibratome also minimized the fracturing of cytonemes that typically occurs when sectioning tissue with a more standard device called a cryostat.

Vibratome sections were visualized using a confocal microscope that combines super-resolution imaging with the ability to track fluorescence lifetime. This approach allowed the

Cam Robinson, PhD, Cell and Tissue Imaging Center, performs metal sputter coating of a sample to increase its conductivity before imaging on the scanning electron microscope.

A St. Jude scientist performs tissue sectioning with a vibratome.

researchers to obtain images with lower background noise and higher spatial resolution. Ogden’s team also used scanning electron microscopy for additional validation that what they observed using light microscopy was occurring at a larger scale.

The researchers were able to observe the tip-to-tip connections made by these cellular extensions in the neural tube, a structure found early in development that eventually becomes the brain and spinal cord. These tipto-tip connections appeared to join cells at the apex of the membranes lining the lumen (hollow space within the neural tube) to primary cilia at the apex of adjacent cells.

Comprehensively, Ogden’s work showed that cytonemes are key contributors to SHH deployment and rapid delivery for tissue patterning. Furthermore, the work showed that when cytoneme function was disrupted, aberrant SHH signaling ensued.

“This is the first demonstration of these cytoneme-based transport processes occurring during the development of a complex mammalian tissue such as the neural tube,” Ogden said.

Lighting the way forward

Illuminating discoveries are often made by pushing past the boundaries of what is known or what already exists to gain new understanding. This mindset of exploration is what enables researchers to gain fundamental biologic insights, whether improving smFRET, creating new tools such as ConVERGD, or seeing structures such as mammalian cytonemes for the first time. By lighting the way forward, these St. Jude researchers are forging the next generation of discoveries.

Advancing biology with intelligent solutions

Clinician scientists gather data about every patient who is treated at St. Jude, ranging from genome sequencing to treatment regimens to medical imaging.

Each experiment performed in St. Jude laboratories — from cell assays to cryo-electron microscopy to transcriptomics — also generates data. Given the amount of information generated, how does St. Jude process, understand, and use these data in the most meaningful and impactful ways? Traditionally, scientists and clinicians have focused only on the data that is relevant to their specific projects. The drawback of this approach is that it can isolate data from other researchers, thereby limiting its potential impact on a broader scale. To unify data across St. Jude, streamline analysis, develop skill and understanding, and unearth patterns that can be useful for biomedical research, St. Jude formed the Office of Data Science.

The Office of Data Science facilitates integrating and analyzing the vast amounts of data collected at St. Jude and helps researchers and clinicians extract meaningful, actionable insights. This innovative approach stands to make St. Jude a global leader in applying data science to biological discovery.

Leading this initiative is M. Madan Babu, PhD, FRS, Chief Data Scientist and Senior Vice President for Data Science. As a member of the Department of Structural Biology and the Director of the Center of Excellence for DataDriven Discovery, Babu will expand the role of data science and data-driven approaches throughout St. Jude.

“With our intellectual ecosystem of talented clinical, experimental, and

With our intellectual ecosystem of talented clinical, experimental, and data scientists united under the same mission, there’s no better place than St. Jude to build a data science enterprise of this magnitude.

M. Madan Babu,

PhD, FRS

Chief Data Scientist & Senior Vice President for Data Science

data scientists united under the same mission, there’s no better place than St. Jude to build a data science enterprise of this magnitude,” said Babu.

Office of Data Science propels innovation

The power of this comprehensive institutional approach is in the collection of large, complex, and unique datasets that can be analyzed to answer a broader scope of biological questions. The Office of Data Science is working with the Information Services department to create an institutional hub in which data are securely housed and easily accessible for researchers wishing to tap into the power of “big data.” Furthermore, Babu and his team are developing ways to ensure the institution has the capacity to meet researchers’ current and future computing needs.

Alongside these endeavors, the Office of Data Science embraces innovation by developing novel computing technologies and optimizing preexisting technologies for

M. Madan Babu, PhD, FRS, has been chosen to lead the St. Jude Office of Data Science.

researchers’ computational workflows. With the establishment of the Office of Data Science, St. Jude will grow its capacity in the areas of artificial intelligence (AI), large language models, computational protein design, and quantum computing.

The push to incorporate innovation has already paid off, as Babu and his team are working to increase the efficacy and predictive power of an AIbased method called AlphaFold2. This software has been integral in predicting protein structure and function. Data scientists successfully integrated this software into the computational

We use AI in radiology to enhance image quality, increase diagnostic accuracy and detection of disease, reduce errors, and improve efficiency and communication.

Andrew Smith, MD, PhD Department of Diagnostic Imaging (Radiology as of Q3 of 2024)

pipeline at St. Jude, and this effort has already shown promise in accelerating the projects of researchers studying a variety of biological questions.

Incorporating AI into medical imaging

The power and potential of AI have implications across departments at St. Jude, including in the Department of Radiology. As the new department Chair, Andrew Smith, MD, PhD, is

integrating AI technology with medical imaging. When speaking of the impact of AI in radiology, Smith said, “Our field leads all other medical fields in the use of AI. We use AI in radiology to enhance image quality, increase diagnostic accuracy and detection of disease, reduce errors, and improve efficiency and communication.”

With assistance from AI, sedation time for patients undergoing positron emission tomography, computed tomography, or magnetic resonance imaging could be decreased as imageprocessing speeds improve. The technology can also ensure that tumor measurements are as accurate and precise as possible, providing valuable information to clinicians creating treatment plans and determining prognoses. An AI approach to pediatric radiology will be transformative, positioning St. Jude as a global innovator of pediatric cancer imaging.

Aligning on data science

The breadth of work at St. Jude is vast and interconnected. The data generated from the clinical and research enterprises are a tremendous asset that needs a team able to shepherd, cultivate, and make the data readily available. Through the

Office of Data Science and the work of Babu, Smith, and other St. Jude researchers invested in these technologies, the insights buried in data can be brought forth. With the true impact of data revealed, we can better understand human health and better serve our mission of advancing cures — and means of prevention — for pediatric catastrophic diseases through research and treatment.

Andrew Smith, MD, PhD, new chair of the Department of Radiology, is integrating artificial intelligence to increase the accuracy and precision of medical imaging.

St. Jude was established in 1962, in part to tackle the daunting task of improving childhood cancer survival, which was just 4%.

Today, with treatment protocols innovated at St. Jude, the five-year survival of the most common pediatric cancer, acute lymphoblastic leukemia (ALL), exceeds 90% in the United States. However, more work remains.

Our scientists are now putting every facet of the rarest and most treatmentresistant leukemia subtypes under the lens to find even the subtlest vulnerabilities and opportunities to improve outcomes for the remaining 10% of pediatric ALL cases.

Scrutinizing B-cell ALL to predict relapse

“ALL treatment is a great success story, but there remains a population of children whose disease is not fully cured,” said Charles Mullighan, MBBS (Hons), MSc, MD, Department of Pathology.

Mullighan co-led a study published in the Journal of Clinical Oncology that addresses the differences in survival

among children with standard-risk B-cell ALL (SR B-ALL) by identifying the genetic predictors of relapse. SR B-ALL is the most common form of pediatric ALL, and as such, nearly half of all relapsed pediatric ALL cases are SR B-ALL. Survival among patients with relapsed or resistant B-ALL falls between 30% and 50%, indicating a dire need for a better understanding of this subgroup.

The scientists conducted wholegenome and -transcriptome sequencing on SR B-ALL samples and compared data from patients who experienced relapse with patients who remained in complete remission. They found that B-ALL subtypes, genetic alterations, and patterns of aneuploidy (extra or missing chromosomes) were associated with the risk of and time to relapse. Some B-ALL subtypes, such as hyperdiploid ALL and ETV6::RUNX1 ALL, had a low frequency of relapse, but others, including PAX5altered, TCF3/4::HLF, ETV6::RUNX1-like, and BCR::ABL1-like ALL, were associated with an increased risk of relapse.

Based on these results, Mullighan suggested, “Children with SR B-ALL should have their tumor cell genome sequenced upon their initial diagnosis to identify if their tumor cells have these high-risk features so that their initial therapy intensity can be increased.”

ALL treatment is a great success story, but there remains a population of children whose disease is not fully cured.

Charles Mullighan, MBBS (Hons), MSc, MD Department of Pathology

A St. Jude patient enrolled in St. Jude Total Therapy XVI clinical trial waits for an appointment in a waiting room.

Higher resolution of gene expression reveals vulnerability in treatmentresistant B-ALL

Understanding the biology of drug resistance in cancer is one of the top research priorities for St. Jude scientists. In Cancer Cell, Jun J. Yang, PhD, Department of Pharmacy & Pharmaceutical Sciences vice-chair, and colleagues reported which B-ALL cells resist treatment and why, as well as a potential counter approach.

“We found a new explanation of B-ALL sensitivity to asparaginase, a drug commonly used for this disease,” said senior co-corresponding author Yang.

“We found leukemic B cells are stuck in two major stages,” said cocorresponding author Jiyang Yu, PhD, Department of Computational Biology interim chair, whose lab investigated gene expression from thousands of cancerous B cells. “One is an earlier stage that is more resistant to asparaginase and another later stage that is more sensitive to it.”

Leveraging single-cell network analysis and drug-sensitivity profiling, Yu and his colleagues discovered that treatment-resistant cancer cells exploit the cell death protein BCL-2 to evade self-destruction. The protein is also downstream of mTOR, asparaginase’s target. This resistance mechanism prompted the scientists to investigate the therapeutic usefulness of venetoclax, a BCL-2 inhibitor. They showed that combining asparaginase with venetoclax was more effective than either drug alone in laboratory models of three high-risk B-ALL subtypes.

“Administering asparaginase alongside venetoclax may reduce the risk of ALL relapse, which is the leading cause of treatment failure,” said co-author Ching-Hon Pui, MD, Department of Oncology. “These findings merit further investigation in future clinical trials.”

Reducing the intensity of B-ALL treatment

“We strive to be mindful, using only the necessary treatments to achieve a cure, so that we can minimize the risk of enduring side effects from a child’s cancer treatment,” said Katelyn Purvis, MD, a pediatric hematologyoncology fellow in the Department of Oncology and first author on a clinical trial study published in Blood designed to determine whether certain B-ALL subtypes can be cured with lower-intensity treatments.

Results showed that patients with ETV6::RUNX1 and high-hyperdiploid B-ALL, which, according to the National Cancer Institute risk assessment, would receive a highintensity treatment regimen, can be treated with a low-intensity regimen and still have positive outcomes.

“In the St. Jude Total Therapy XV and XVI studies, we incorporated genetic information and response criteria into our risk assessment. This risk classification system allows us to identify patients who can be treated with lower-intensity therapies while

We incorporated genetic information and response criteria into our risk assessment [which] allows us to identify patients who can be treated with lowerintensity therapies while ensuring those who require more intensive treatment receive it.

Hiroto Inaba, MD, PhD Department of Oncology

ensuring those who require more intensive treatment receive it,” said corresponding author Hiroto Inaba, MD, PhD, Department of Oncology.

A St. Jude patient attends a checkup appointment with Hiroto Inaba, MD, PhD, Department of Oncology, who finds some time to have fun with him too.

Patients who would have otherwise received high-risk therapy experienced fewer side effects, such as thrombosis and pancreatitis. The findings suggest that clinicians can accurately identify patients likely to benefit from less intensive treatment by using genome- and early treatment response–guided risk classification.

Focusing on single nucleotides in DNA to predict and treat disease

While much research focuses on understanding B-ALL genetics after diagnosis, scientists can apply the same techniques to predict if a child is at a higher risk of cancer before it develops. In a study published in Blood, St. Jude researchers characterized variants in a single gene in children with B-ALL to determine which were risk factors for the disease.

“We found NBN is a key B-ALL risk gene,” Yang, the corresponding author, said. “We identified many genetic variants in this gene that seemed to be linked to B-ALL, and

we meticulously characterized their functional consequences.”

The researchers sequenced NBN in 4325 patients with B-ALL and found 25 unique, putatively damaging coding variants in 50 patients. These variants were overrepresented in children with this form of leukemia, suggesting that they predispose people to the disease.

Testing these variants in the lab, the scientists found that 14 variants caused severe loss of function of the protein encoded by NBN. NBN is involved in double-stranded DNA repair, so the loss of its activity provides a plausible mechanism for increased cancer incidence. However, NBN loss also represents a potential challenge for treating leukemia.

“As NBN is involved in DNA repair and many leukemia drugs cause DNA damage, we did worry that patients with variants would experience higher treatment-related toxicity,” Yang said. “But that did not seem to be the case, although the number of patients we studied was relatively small.” The researchers found that the survival of these patients was comparable

to that of patients without NBN variants, suggesting that patients with NBN variants can safely receive standard B-ALL care and experience a reasonable treatment outcome.

We found NBN is a key B-ALL risk gene [and] identified many genetic variants in this gene that seemed to be linked to B-ALL, [then] we meticulously characterized their functional consequences.

Jun J. Yang, PhD

Department of Pharmacy & Pharmaceutical Sciences

Fine-tuning treatment for T-cell ALL

Childhood T-cell ALL (T-ALL) is an aggressive cancer that typically responds well to initial treatment, but relapsed T-ALL and treatment-resistant disease have dismal prognoses. Given its relative rarity, studying T-ALL genetics has been difficult. To address that need, St. Jude collaborated with other pediatric research hospitals to profile the whole germline and cancer genomes of more than 1300 children, adolescents, and young adults with T-ALL.

As published in Nature, T-ALL was classified into 15 subtypes with distinct gene expression and genomic drivers, including previously undefined subtypes. The researchers also refined the classification of known subtypes and showed that driver lesions, other genetic changes, and the original cell type cooperate to define the genomic subtype and a condition’s clinical and biological characteristics. They also observed a significant link between the kind of gene alterations and outcomes in T-ALL.

The study found that approximately 60% of the genetic changes driving T-ALL cells are noncoding changes.

“It was striking how abundant these noncoding changes were and how many of them were enhancer-

perturbation events,” Mullighan, a co-corresponding author, said. “We now have a much stronger framework to take these alterations back to the lab, build the right models to understand the biology, and test therapy.”

Focusing on the rarest T-ALL subtypes

Investigators from St. Jude and an international collaborative group of more than 50 researchers joined forces to understand the rare but aggressive gamma delta T-cell ALL (γδ T-ALL). In Cancer Discovery, they reported identifying 200 children with γδ T-ALL, the largest cohort of the disease.

“We needed a large collaborative effort to understand the genetics in these cases to figure out how to potentially treat them,” cocorresponding author Inaba said.

The researchers found that genetic alterations resulting in activation of LMO2, a gene commonly altered in other types of T-ALL, and inactivation of STAG2, a gene more commonly altered in acute myeloid leukemia (AML) and solid tumors, were associated with worse outcomes.

“This alteration switches STAG2 off, taking the STAG2 promoter and moving it proximal to LMO2, switching it on,” Mullighan, a co-corresponding author,

said. “This dual mechanism is unusual and provides insight into what happens at the genomic level in this rare cancer.”

That insight also highlighted potential treatment strategies, informing drug-screening design to identify therapeutics that may help treat γδ T-ALL. PARP inhibitors, which target dysfunctional DNA-repair pathways in cancer cells, showed some promise. STAG2 is an important protein that acts as a subunit of the cohesin complex, which stabilizes DNA replication forks and helps maintain chromosomes. When STAG2 is mutated, doublestranded DNA breaks become more common. PARP inhibitors could plausibly target STAG2’s functional defect, accelerating DNA damage accumulation and driving cancer cells toward self-destruction.

Inaba expressed optimism about PARP inhibitors, “This is very exciting to identify a potential targeted therapy for these patients who have typically poor outcomes.”

Taking a microscope to pediatric AML

Despite constituting only 20% of pediatric acute leukemias, pediatric acute myeloid leukemia (pAML) remains the leading cause of mortality among children with leukemia. However, “most of what we know about classifications

(Left) A St. Jude scientist looks at pathology slides for pediatric acute myeloid leukemia (pAML). (Right) A St. Jude scientist loads a gel.

Most of what we know about classifications of AML comes from the adult field. Many of the AML types we see here at St. Jude, you just don’t see in adults.

Jeffery Klco, MD, PhD Department of Pathology

of AML comes from the adult field,” said Jeffery Klco, MD, PhD, Department of Pathology, who led a study published in Nature Genetics to define the molecular underpinnings of pAML.

“Many of the AML types we see here at St. Jude, you just don’t see in adults.”

Therefore, the researchers examined 887 unique pAML cases via transcriptome and gene profiling. The findings established 23 distinct molecular categories, including 12 not included in the current classification systems.

Their results showed that while the normal accumulation of mutations during aging may explain many adult AML cases, fusion oncoproteins are major drivers in more than 70% of pAML cases. “Some categories show very similar transcriptional profiles, indicating that the background biology is similar and can potentially be treated by similar drugs,” said first author Masayuki Umeda, MD, PhD, a postdoctoral fellow in the Department of Pathology.

By combining the transcriptome and gene profiling analysis with clinical data, the researchers determined a strong association between the new pAML subtypes and clinical outcomes.

“The study fills many gaps in the current classification of pAML,” first author

Jing Ma, PhD, a principal bioinformatics research scientist in the Department of Pathology, confirmed. “It provides a risk-stratification strategy we hope will provide clinicians with a simpler road to accurate diagnosis and optimal treatment in the future.”

Bringing an important AML subtype into focus

A gene fusion called PICALM::MLLT10 (PM) is a rare but recurring genetic driver associated with different acute leukemia subtypes. PM-positive AML (PM-AML) is uncommon and accounts for less than 1% of pediatric cases but has particularly poor outcomes. St. Jude scientists compared the genetic and transcriptomic profiles of PM-AML and T-cell acute lymphoblastic leukemia/ lymphoma with PM fusions (PM –T-ALL/ LLy) to “identify subtype-specific molecular signatures that could offer insights into disease development, progression, and potential therapeutic targets,” said co-author Rebecca Voss, MD, an associate scientist in the Department of Pathology.

Published in Leukemia, results show that among patients with PM-AML, there is a high frequency of alterations in TP53 and NF1, which normally help prevent cancer. “The most compelling finding from our study was that patients with AML with this fusion typically have cooperating mutations in the TP53 gene, which you don’t particularly see in T-ALL cases,” co-author Klco said.

Additionally, investigators found that PHF6 was the most frequently mutated gene in this study cohort, occurring in both PM-AML (approximately 70%) and PM–T-ALL/LLy (37.5%). PHF6 is an epigenetic remodeler that regulates gene expression.

“PHF6 alteration is commonly associated with T-ALL, so finding its high frequency in PM-AML cases was quite surprising, suggesting it plays a key role cooperating with the PICALM::MLLT10 fusion in leukemogenesis, particularly in PMAML,” said corresponding author

Lu Wang, MD, PhD, Department of Pathology. The elevated expression of specific HOXA genes and XPO1 demonstrated in this study supports the potential use of Menin inhibitors and SINEs (short, interspersed nuclear elements) for treating these rare and challenging forms of leukemia.

Our study reveals a unique molecular landscape in PMAML and underscores the need for further investigation into its underlying molecular pathogenesis.

Lu Wang, MD, PhD Department of Pathology

“Overall, our study reveals a unique molecular landscape in PM-AML and underscores the need for further investigation into its underlying molecular pathogenesis,” said Wang.

Assembling the bigger picture of pediatric leukemia

By looking ever more closely at rare and relapsed leukemia subtypes, investigators at St. Jude are discovering how to treat these cancers more effectively. Until the cure for leukemia reaches 100%, scientists will keep putting leukemia under the lens — increasing scrutiny to detect the smallest features of these diseases that can be leveraged therapeutically.

Cracking the chromatin code

From bank statements to email, computer programs use passwords to secure important information. Cellular programs also secure information in chromatin, the complex of DNA and its associated proteins.

Cells use “biochemical passwords” comprising chemical modifications and interactions among proteins to allow or restrict access to specific genes within chromatin. St. Jude researchers are identifying how cancer cells crack the chromatin code to steal or mimic these passwords and how scientists can hack that same code to stop — or even revert — pediatric cancers.

Stealing the serotonin password for growth

Ependymoma, the third most common type of brain tumor in children, has no known effective therapeutic targets. In collaboration with Baylor College of Medicine, Stephen Mack, PhD, Department of Developmental Neurobiology, and his colleagues engineered a mouse model of the cancer and found how aberrant neuronal activity impacts ependymoma cells by regulating pro-tumor genes wrapped in chromatin. The study, published in Nature, revealed an unexpected mechanism that may be a target for future therapies.

The research revealed that serotonin transporters are enriched within tumor cells with the ZFTA–RELA gene fusion, implying that the tumor cells forage serotonin from their environment. Serotonin was imported into ependymoma cells and attached to the histones that make up chromatin, a process called serotonylation. The presence of the ZFTA–RELA fusion protein and serotonylation allowed full access to the proliferative genes, thereby aiding tumor growth.

Finding that histone serotonylation regulates tumorigenesis and that it’s being driven by neurons in the microenvironment is remarkable, it could apply to other tumor types too.

Stephen Mack, PhD Department of Developmental Neurobiology

“Finding that histone serotonylation regulates tumorigenesis and that it’s being driven by neurons in the microenvironment is remarkable,” said Mack. “It could apply to other tumor types too.” Neuromodulatory agents, such as selective serotonin reuptake inhibitors (SSRIs), are currently used to treat certain mental health conditions. Although these agents have not been tested on brain tumors, the findings suggest they are an avenue worth exploring.

Scientists hack cancer back

Therapeutic targeting of mutant genes is a promising frontier in the fight against cancer; however, many cancers are caused by the complete loss of a gene. This is a challenge for researchers because, in those cases, the protein encoded by the gene is no longer present to be targeted. Loss of the tumor-suppressor protein SMARCB1 is implicated in rhabdoid tumors, which comprise aggressive cancers that primarily affect infants and very young children. St. Jude researchers led by Charles W.M. Roberts MD, PhD, executive vice president and St. Jude Comprehensive Cancer Center director, were looking for a way to treat aggressive rhabdoid tumors caused by the loss of SMARCB1 when they found a new approach to treatment.

Published in Nature, the study showed that a little-studied protein, DCAF5, is essential to rhabdoid tumors missing SMARCB1. Initially, the team identified DCAF5 as a target by using the Dependency Map (DepMap) portal, a database of cancer cell lines and genes critical for their growth. When the scientists genetically deleted or chemically degraded DCAF5, the cancer cells reverted to a noncancerous state, resulting in the sustained remission of the cancer in the mouse model. “We saw a spectacular response,” said Roberts. “The tumors melted away.”

Normally, SMARCB1 is an essential component of a larger chromatinregulating complex of proteins called the SWI/SNF complex. Unexpectedly, the study found that in the absence of SMARCB1, DCAF5 recognizes SWI/ SNF as abnormal and destroys the complex. The researchers showed that when DCAF5 is degraded, SWI/ SNF re-forms and maintains its ability to open chromatin and regulate gene expression to an extent sufficient to reverse the cancer state fully.

“The mutation of SMARCB1 shuts off gene programs that prevent cancer. By targeting DCAF5, we’re turning those

Myriad types of cancers are caused by tumor suppressor loss. We hope we have opened the door to thinking about new ways to target at least some of these by reversing, instead of killing, cancer.

Charles W.M. Roberts, MD, PhD

Executive Vice President, Director of the St. Jude Comprehensive Cancer Center

gene programs back on,” said first author Sandi Radko-Juettner, PhD, a former St. Jude Graduate School of Biomedical Sciences student, now a research program manager for the Hematological Malignancies Program.

“We have demonstrated a beautiful proof of principle,” Roberts said. “Myriad types of cancers are caused by tumor suppressor loss. We hope we have opened the door to thinking about new ways to target at least some of these by reversing, instead of killing, cancer.”

Revealing vulnerabilities in two-factor authentication for a cell growth program

In another study, Roberts’s team again leveraged DepMap to systematically identify genes that become essential to cancer cells when SMARCB1 is absent because those genes present potential routes for future targeted therapies.

“We discovered PHF6 as another one of those genes,” said Roberts. “We found that in healthy cells, PHF6 co-

localizes with SMARCB1 and helps the SMARCB1-containing SWI/SNF complex keep chromatin open, which then becomes aberrant without SMARCB1.”

In healthy cells, SMARCB1 and PHF6 act like two-factor authentication, both of which are necessary for genes to be turned on. Although SMARCB1 loss promotes cancer, its absence should shut down the expression of so many genes that the cell would die. When SMARCB1 is lost, PHF6 keeps many of those genes turned on, allowing the cancer cells to survive. Removing PHF6 from these cells caused cell death and slowed or stopped tumor growth, revealing a potential vulnerability to target in rhabdoid tumors and possibly other cancers.

“Twenty percent of cancers have mutations in SWI/SNF subunits,” Roberts explained. “This work on dependencies could advance the opportunity to find therapeutic interventions far more broadly than just rhabdoid tumors.”

The future of chromatin research at St. Jude

The tight regulation of chromatin protects cells from carrying out potentially harmful gene expression programs while promoting the expression of protective genes, such as tumor suppressors. These fundamental processes often go awry in pediatric cancer, highlighting the tremendous opportunity to leverage chromatin control therapeutically.

St. Jude scientists are well poised to continue cracking the chromatin code, finding new targeted therapies for some of the most difficultto-treat pediatric cancers.

tending to the Root

OF HEALTH TO PREDICT AND PREVENT DISEASE

Living things all have needs, such as water, sunlight, or nutrients. Tending to the root of health means addressing the foundational factors, such as genetics or the environment, that shape these needs and impact health.

Predicting, preventing, and intervening against disease ensures that children at risk of negative health outcomes receive the proper care under the right conditions to thrive. At St. Jude, scientists are studying how to predict who is at risk of disease and which interventions will be most beneficial to prevent diseases from occurring in the first place.

Putting kids first in cancer detection and prevention

Disease detection is entering a golden era where sophisticated classification strategies and genetic screening panels fuel the development of novel detection methods that can lead to better outcomes for patients.

Physicians use this knowledge to tailor targeted treatments to the specific cancer-causing mutations affecting each patient. However, current high-quality wholegenome sequencing requires physical and computational infrastructure that most institutions lack. To address this bottleneck, Xiaotu Ma, PhD, Department of Computational Biology; Jeffery Klco, MD, PhD, Department of Pathology; and John Easton, PhD, Computational Biology Genomics Laboratory director, developed SJPedPanel. Published in Clinical Cancer Research, SJPedPanel is a sequencing platform focusing on genes involved in childhood cancer instead of looking at the entire genome.

Even though adult cancers are genetically distinct from childhood malignancies, all available genetic screening panels were designed for adult cancers and then adapted for pediatric cancers. St. Jude was one of two institutions that conducted the Pediatric Cancer Genome Project, which sequenced the genomes of 800 patients whose diagnoses included 23 types of cancer to provide the most detailed overview of the genomic landscape of many pediatric cancers. The SJPedPanel covers the risk-related genome regions, occupying just 0.15% of the genome, to provide a comprehensive assay to detect the full spectrum of mutations in pediatric cancers.

“We compared this panel with six commercially available panels,” Ma said. “SJPedPanel provides the most coverage of pediatric cancer driver genes, providing close to 90% when others are closer to 60% coverage.”

In addition to working better than adapting adult-focused cancer

gene panels, the SJPedPanel outperforms gold-standard wholegenome sequencing in some circumstances. Whole-genome sequencing interrogates the entire human genome, making detecting low–cell-count cancers difficult.

“There are certain situations, such as low tumor purity samples or even testing after bone marrow transplantation, where current clinical whole-genome sequencing approaches don’t work,” Klco said.

“This fills an important clinical gap for our patients.” SJPedPanel is now part of the routine clinical service at St. Jude and will soon be used to monitor patient response during therapy.

The panel will give institutions without resources, such as wholegenome sequencing, a better chance at identifying cancers.

“Panels like the SJPedPanel are easier for clinical or research labs to implement than whole-genome sequencing,” Easton said.

SJPedPanel provides the most coverage of pediatric cancer driver genes, providing close to 90% when others are closer to 60% coverage.

Xiaotu Ma, PhD Department of Computational Biology

Detecting cancer resistance to prevent the spread of disease

Detecting cancer before it can spread is critical to ensuring overall and longterm health. Even if interventions work on most of a tumor, biological resistance means small populations of cancer cells often survive, and those cells are more challenging to treat. Determining how these robust malignant cells escape treatment is key to true prevention.

The survival of children with relapsed or recurrent ALL is 30% to 40%, often due to therapy resistance. In research published in Nature Communications, Daniel Savic, PhD, Department of Pharmacy & Pharmaceutical Sciences, identified and investigated mechanisms behind functional variants within the noncoding region of the genome and explored their contribution to resistance using six drugs that treat leukemia. Despite being devoid of genes, the noncoding region of the genome comprises 98% of DNA and contains a vast number of gene

We harnessed innovative tools and technologies to systematically examine the noncoding genome and understand its functional effects on ALL pharmacogenomics.

Daniel

Savic, PhD Department of Pharmacy & Pharmaceutical Sciences

regulatory elements, some of which could contribute to resistance.

By combining massively parallel reporter assays and three-dimensional chromatin looping assays, the St. Jude researchers identified more than 1600 inherited noncoding variants associated with drug resistance in ALL with gene-regulatory roles. This comprehensive study, the largest of its kind to date, prioritized 556 functional noncoding DNA variants that affected gene regulation related to ALL drug resistance in at least three ALL cell lines, identifying a previously unknown resistance mechanism to the chemotherapy drug vincristine. This finding was based on a functional interrogation of the most robust variant, linking its proximity to the gene for EIF3A, a protein involved in cell proliferation and survival, to its resistance mechanism.

“In any genome-wide association study, nearly all associated genetic variants reside in the noncoding genome, so connecting that variation to gene function and an actual trait, such as

Jun J. Yang, PhD, Departments of Pharmacy & Pharmaceutical Sciences and Oncology, examined pediatric and adult B-cell acute lymphoblastic leukemia to assess their differential responses to therapies.

chemotherapy resistance or disease predisposition, is challenging,” Savic said. “We harnessed innovative tools and technologies to systematically examine the noncoding genome and understand its functional effects on ALL pharmacogenomics. We hope to utilize our findings to improve clinical outcomes in ALL patients.”

Understanding the relationship between genetics and treatment response

Genetics can directly affect how patients respond to treatments and interventions. Acute lymphoblastic leukemia (ALL) affects both children and adults. Children with ALL have a better chance of being cured than adults; long-term survival of childhood ALL exceeds 90%, compared to that of adults, which is 50% to 75%. However, whether ALL has an age-related drugresponse profile is unclear. In a study published in the Journal of Clinical Oncology, a team led by Jun J. Yang,

PhD, Departments of Pharmacy & Pharmaceutical Sciences and Oncology, examined 767 children and 309 adults with B-cell ALL, assessing the sensitivity of leukemia cells to 21 drugs.

“We found that, for most of the cytotoxic drugs with differential activity between adult and pediatric, it’s largely explained by the age-related differences in the underlying genomic abnormalities of their cancer, namely molecular subtypes,” Yang said.

However, the molecular subtypes of ALL did not explain all the differences in antileukemia drug sensitivity between children and adults. The researchers found that some children had “adultlike” ALL based on their gene expression profiles, making them more resistant to treatment and leading to poorer outcomes. This finding suggests that age and individual genomics beyond the ALL subtype must be considered to predict treatment response.

“There’s a lot of heterogeneity within each age group,” explained Yang. “You cannot simply divide patients

into older than or younger than 18 years and offer therapy based on the legal age of majority; you have to look at their underlying molecular characteristics and pharmacogenomic features.” Together, the group’s findings suggest the need for tailored treatment strategies for both children and adults with B-cell ALL.

DNA reveals predisposition in survivors of childhood cancer

Genetic predispositions are found in 5% to 15% of children with cancer. In a study published in JAMA Oncology, Kim Nichols, MD, Division of Cancer Predisposition director, Department of Oncology, showed that beginning surveillance soon after recognizing a patient’s predisposition often leads to discovering one or more early-stage asymptomatic tumors, most of which could be removed after chemotherapy and/or radiation therapy, and about half of which could be removed surgically.

The researchers examined 274 pediatric patients at St. Jude who carried 35 different cancer-predisposing syndromes over a median of three years. Surveillance revealed 35 tumors in 27 patients, representing a broad array of solid and central nervous system cancers. This group included a subset of about 17% of children who had a new tumor identified while they were still undergoing treatment for a prior cancer. This finding suggests providers should not wait until a child has finished treatment for their first cancer before they start screening for other potential malignancies.

To find potential cancers and guide treatment, clinicians used various surveillance methods. For example, a predisposition for a solid tumor may lead to annual full-body magnetic resonance imaging (MRI). Standard surveillance methods had minuscule false positive and false negative rates.

Understanding whether children have an underlying genetic risk for cancer can greatly impact their clinical care. Proactive surveillance for new tumors is an important component of this care.

Kim Nichols, MD Department of Oncology

data collections, such

Comprehensive

as the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort Study, allow scientists to piece together the genetic risks of surviving pediatric cancer.

“We’ve shown that standardized surveillance protocols provide a very effective way to detect new tumors at their earliest and most treatable stages,” Nichols said. “Understanding whether children have an underlying genetic risk for cancer can greatly impact their clinical care. Proactive surveillance for new tumors is an important component of this care.”

The study may enable more providers to order these effective, yet sometimes expensive, tests. It can be challenging for providers to get insurance companies to pay for early screening. Historically, this has created a difficult cycle where providers could not order the tests, which meant there was no strong evidence of their value, preventing their use. Patients at St. Jude are treated regardless of insurance coverage, thus enabling physicians to order the appropriate tests. The excellent performance of the standard screening methods is evidence that early testing can improve detection and outcomes. This may give insurance companies the evidence needed to cover the tests for children with a predisposition.

Avoiding longterm effects of cancer on health

Cancer has lifelong effects. Survivorship research focuses, in part, on predicting and preventing these long-term adverse effects. Published in the Journal of Clinical Oncology, a study led by Yadav Sapkota, PhD, Department of Epidemiology & Cancer Control, identified four previously unknown genetic variants associated with diabetes risk in childhood cancer survivors. Furthermore, the genetic risks for diabetes appeared to be not only magnified by childhood exposure to alkylating agents (a common class of chemotherapeutics) but also exacerbated by ancestry.

“The genetic risk disproportionately affected survivors of African or African American ancestry previously treated with alkylating agents,” Sapkota said.

“The same variant is implicated in both European and African ancestry groups, but the amount of risk conferred by carrying the variant differs.”

In addition to individual genetic variants, combinations of many genetic variants previously associated with diabetes risk in the general population, considered as a score, have been studied to assess disease risk in childhood cancer survivors. However, these scores have been derived typically from studies involving only individuals of European descent. Thus, the researchers compared three scores: one based on those of European descent only and two others developed by including individuals of different ancestries. The more inclusive scores more accurately predicted diabetes risk in survivors of both European and African ancestries.

Now we know how to identify childhood cancer survivors most at risk of diabetes so we can provide more personalized opportunities for interventions and prevent cardiovascular complications down the road.

Yadav Sapkota, PhD Department of Epidemiology & Cancer Control

“We hope this information will help reduce differences in the diabetes burden,” Sapkota said. “Now we know how to identify childhood cancer survivors most at risk of diabetes, so we can provide more personalized opportunities for interventions and prevent cardiovascular complications down the road.”

Minimizing symptom burden to maximize quality of life

While detecting disease risk is at the root of improving clinical outcomes, long-term monitoring is required for quality-of-life improvements to endure. Treatment for medulloblastoma, a type of childhood brain tumor, is associated with neurocognitive impairments. The outlook for patients with medulloblastoma has improved over time. However, Tara Brinkman, PhD, Departments of Psychology & Biobehavioral Sciences and Epidemiology & Cancer Control, and her colleagues showed in research published in Neuro-Oncology that the risk of neurocognitive impairment remains a concern.

The researchers surveyed 505 survivors of medulloblastoma from the Childhood Cancer Survivor Study (CCSS), a multiinstitution retrospective cohort with prospective follow-up led by Gregory Armstrong, MD, MSCE, Department of Epidemiology & Cancer Control chair. They categorized the participants based on the treatment received.

Childhood medulloblastoma survivors who were treated between 1970 and 1999 experienced as much as a fivefold increased risk of cognitive deficits compared to that of their healthy siblings. Notably, the researchers observed that the survivors’ ability to achieve independence in adulthood is adversely impacted by the development of neurocognitive problems and chronic health conditions after treatment for medulloblastoma.

“Routine surveillance of neurocognitive functioning in survivors remains critical

to understanding the long-term effects of contemporary therapies,” Brinkman said. “Surveillance efforts further inform our ability to prevent and manage disease and treatment-related late effects to optimize quality of life.”

In addition to how clinical factors affect patient outcomes, research on how contextual factors such as low socioeconomic status, unstable housing, and transportation barriers affect the health of childhood cancer survivors mainly focused on those survivors who reached adulthood. This approach has left a gap in understanding the experiences of children and adolescents at least five years postdiagnosis and younger than 18 years.

Published in JAMA Network Open, a study by I-Chan Huang, PhD, Department of Epidemiology & Cancer Control, examined the physical and psychological symptoms in children and adolescents aged 8 to 18 years and explored the contextual factors’ impacts. This involved identifying associations with sociodemographic, clinical, and psychological resilience skills and health-related quality of life. The study provides a comprehensive portrait of the challenges faced by young survivors and suggests ways to develop targeted interventions.

By examining contextual factors in 302 young childhood cancer survivors, the investigators found that nearly 40% of the cohort self-reported moderate or high cumulative overall symptom burden. Factors that correlated strongly with symptom burden included caregiver anxiety and neighborhood deprivation, which cover aspects such as income and living environment. “If parents have anxiety, there is almost a two-fold higher risk that survivors will have a higher symptom burden,” Huang explained. This conclusion is compounded by evidence showing that children living in high-vulnerability neighborhoods have a five-fold higher risk of experiencing high symptom burden.

The study identified preventative factors that can mitigate symptom

Routine surveillance of neurocognitive functioning in survivors remains critical to understanding the long-term effects of contemporary therapies.

Tara Brinkman, PhD Departments of Psychology & Biobehavioral Sciences and Epidemiology & Cancer Control

burden. For example, “We found the association between parents’ anxiety and the survivor’s disease burden decreases with high levels of survivor resilience,” said Huang. A sense of resilience reduced the impact of negative contextual factors on symptom burden by 30% to 40%.

However, while the survivor’s resilience can mitigate personal and family issues, community factors need broader solutions. “We need to find a way to identify and screen for the origin of their symptoms, then provide the necessary intervention,” Huang said.

Patient-reported outcomes are a key metric to understanding symptom burden, but clinicians are limited by the frequency of assessments — often only once every couple of years. “I don’t believe using these snapshots to understand symptom burden is enough,” Huang said. “I want to see the dynamics of the symptoms and how they evolve over time.”

In a pilot study of 41 participants published in Cancers and a larger

St. Jude investigator I-Chan Huang, PhD, is leading research using wearable devices that track variables such as heart rate, helping gather important data about the health of childhood cancer survivors.

study protocol involving 600 survivors described in Frontiers in Oncology, Huang explored utilizing mobile health technology (mHealth) to achieve this. The researchers collected daily symptom data, momentary digital biomarkers (e.g., heart rate variability, respiratory rate, skin temperature, etc.), and overall progression of late effects over five years. The mobile platform enabled the researchers to send symptom and quality-of-life surveys to participants daily, which prompted them to report on 20 symptoms. They also tracked digital biomarkers through wearable activity monitors.

The researchers noted that some symptoms remained stable, but many demonstrated high variability from day to day, month to month, and even between individuals. “It suggests that we need more frequent symptom assessments rather than relying on yearly or less frequent clinic visits,” said Huang. “This also means that intervention strategies should be tailored to account for this variability.”

I want to see the dynamics of the symptoms and how they evolve over time.

I-Chan Huang, PhD Department of Epidemiology & Cancer Control

To collect robust data, using wearable devices represents a key feature of the study to Huang. “Combining wearable device data, such as heart rate, activity levels, and sleep patterns, with selfreported symptom data allows us to

identify patterns,” Huang said. “We can then predict various disease progression outcomes and integrate this prediction algorithm into the clinical workflow as a key component of the clinical warning system for managing late effects.”

Providing a blueprint for prediction and prevention

While there is no exact blueprint for human health that will tell providers exactly who is at risk of disease or how to treat them, scientists are working to fill in gaps in knowledge, giving providers clues about the factors that influence health and how they can be assessed, modified, and used to tailor care for each person. A vast array of factors shape a person’s health, and with the right interventions, challenges can be overcome. Just as a plant with proper care can flourish despite harsh conditions, children can thrive when the root factors that shape their health care outcomes are understood.

Keeping the (heart)beat strong after pediatric disease

A healthy heart is vital, but for survivors of catastrophic pediatric illnesses such as cancer and people with sickle cell disease, maintaining a healthy heart can be a challenge.

Sickle cell disease causes red blood cells to clump together and clog blood vessels, potentially resulting in heart injury and myocardial fibrosis (scar tissue buildup). “Sickle cell disease chips away at the wall of your health one brick at a time,” said Akshay Sharma, MBBS, MSc, Department of Bone Marrow Transplantation & Cellular Therapy.

Bone marrow transplantation is used to cure sickle cell disease, but myocardial fibrosis was thought to be irreparable by the treatment. Research published in Blood by Sharma and collaborators showed that not only did heart function recover, but myocardial fibrosis damage was reversed, which no disease-modifying treatment has previously achieved.

Early detection reduces long-term risk

While myocardial fibrosis can be reversed, cardiovascular risk in survivors of pediatric cancer may not be fully realized until they are older. A study in The Lancet Oncology led by Greg Armstrong, MD, MSCE, Department of Epidemiology & Cancer Control chair, showed that by age 50, survivors experience a cumulative incidence of major adverse cardiovascular events (MACE) almost 20 times higher than average. Frequent screening was shown to detect this increased risk for

MACE. This suggests that proactive screening can help risk management since these conditions are detectable by electrocardiogram or echocardiography.

“Clinicians need to be aware that cancer survivors are at higher risk than the general population,” said Armstrong. “They should screen survivors appropriately and maintain a low threshold for referral to a cardiologist.”

Early detection can also help prevent other long-term heart risks among survivors. In the Journal of Clinical

Oncology, Stephanie Dixon, MD, MPH, Department of Oncology, showed a high prevalence of prediabetes in young adult survivors, which increases their risk of diabetes and related cardiovascular and kidney disease.

“We need to help survivors understand that prediabetes is an early warning sign that should lead to a change, whether that’s lifestyle, medication, or close primary care follow-up,” Dixon said. “But that change starts with physicians identifying when a survivor has developed prediabetes.”

Pediatric diseases elevate cardiovascular risk, but St. Jude researchers are pioneering efforts to help patients and clinicians understand and address this challenge.

Preventing heart disease before

it manifests

Estimating the risk of cardiovascular diseases isn’t straightforward, as many are asymptomatic until a severe event occurs. In a study published in the Journal of Clinical Oncology, Matthew Ehrhardt, MD, MS, Department of Oncology, found that two common biomarkers, global longitudinal strain (GLS) and N-terminal-pro-

B-type natriuretic peptide (NTproBNP), could identify survivors with normal appearing heart function at elevated risk of heart disease.

GLS measures the heart muscle’s ability to contract and relax with each cycle via echocardiogram. NT-proBNP is a serum biomarker released into the bloodstream when the heart is injured or overworked.

“The increased risk of developing cardiac dysfunction observed in individuals with abnormal GLS and

Clinicians need to be aware that cancer survivors are at higher risk than the general population. They should screen survivors appropriately and maintain a low threshold for referral to a cardiologist.

Gregory Armstrong, MD, MSCE Department of Epidemiology & Cancer Control

NT-proBNP supports investigating early interventions to prevent heart failure progression,” said Ehrhardt.

By studying the impact of treatments, early detection, and interventions, St. Jude researchers are making significant strides toward preserving and protecting the heart health of survivors of pediatric disease.

ADVANCES IN FUNDAMENTAL BIOLOGY AND IMMUNOTHERAPY

T cells are the body’s frontline protectors, pivotal in the immune system’s defense against disease.

Understanding T-cell biology is of great significance for immunotherapy, in which genetically modified T cells have demonstrated potential to treat cancers once considered incurable.

However, while these therapies have offered a chance at remission to some patients, they have not been universally successful.

The challenge of immunotherapy lies in optimizing T-cell performance — enhancing their activation, longevity, and function to ensure they respond robustly and sustainably.

Understanding these processes is central to improving immunotherapies as researchers explore ways to “finetune” T cells, thereby preventing their limitations and ensuring they function at their peak for longer periods.

At St. Jude, researchers harness the power of T cells by diving deep into their biology and discovering how to enhance their precision and persistence. These advances are opening the door to more effective therapies, bringing us closer to harnessing the power of the immune system to target and destroy tumors with minimal side effects.

Our research uncovers the mechanisms by which T cells adjust to extracellular nutrient conditions and connects these mechanisms to a key intracellular organelle, the lysosome.

Hongbo Chi, PhD Department of Immunology

Scientists at the Hartwell Center for Biotechnology use state-of-the-art equipment to perform microarray analyses.

Foundations of tissueresident and regulatory T-cell function

To better understand and optimize the therapeutic application of T cells in cancer and other diseases, researchers at St. Jude use fundamental T-cell biology to unlock new ways to enhance immune efficacy. Hongbo Chi, PhD, Department of Immunology, studies metabolic systems and signaling pathways in T cells and capitalizes on those pathways to harness T cells’ antitumor and tissue immunity functions.

“T cells migrate to various tissues and must adapt to the local nutrient environment. Our research uncovers the mechanisms by which T cells adjust to extracellular nutrient conditions and connects these mechanisms to a key intracellular organelle, the lysosome,” Chi explained.

immune responses to nutrient availability and lysosomal function.

These findings, published in Immunity, highlight the complex interplay between metabolism and T-cell function and offer new insights into how T cells can be optimized to improve immune responses in tissues.

T-cell function is governed by metabolism and the ability to distinguish self from non-self, a process overseen by regulatory T (TREG) cells. The protein Foxp3 serves as a gatekeeper, or master regulator, determining what the immune system recognizes as “self” to protect from attack. However, the exact mechanism behind this process has remained elusive.

Tissue-resident memory (TRM) and TRM–like cells provide rapid, localized immune responses at the site of infection or tumor growth. Chi’s team used CRISPR-Cas9 genetic screens to uncover critical signaling pathways influencing TRM cell development and differentiation. They found that TRM cell formation depends on processes in cellular organelles called mitochondria. Additionally, signaling nodes at the lysosome, such as Folliculin (Flcn), Ragulator and Rag GTPases, restrict TRM formation and development.

Apart from organelle signaling, the study also found that nutrient availability played a role in tissue immunity. Specifically, Flcn modulates the activity of transcription factor EB (Tfeb). Flcn–Tfeb signaling, induced by amino acid deprivation, contributes to TRM cell development. The relationship links nutrient stress to cell fate decisions. Therefore, the Flcn–Tfeb axis is a regulatory pathway that coordinates

As immunologists, we don’t just want to understand the mechanisms; we want to know how we can take advantage of this knowledge to engineer better therapies.

Yongqiang Feng, PhD Department of Immunology

A study led by Yongqiang Feng, PhD, Department of Immunology, and published in the Journal of Experimental Medicine, examined Foxp3. For decades, Foxp3 has been considered a transcription factor, a protein that coordinates gene expression. The tunable nature and broad swath of responses that Foxp3 controls led Feng to question the biochemical nature of how this transcription

Microarray analysis allows the exploration of gene expression and epigenetic changes in T cells, offering valuable insights into their biology.

factor itself was regulated. How did Foxp3 know whether to coordinate a suppressive immune response?

The researchers studied the relationship between Foxp3’s protein-binding partners and its function, making a surprising discovery. “We found that when the environmental conditions changed, the ability of Foxp3 to interact with DNA also changed,” Feng said. “We found the Foxp3 does not directly interact very much with the DNA but rather binds to other DNA-binding proteins. In this sense, it is a transcriptional cofactor.”

These findings suggest that environmental triggers activating regulatory T cells drive the expression of Foxp3’s binding partners, which then coordinate with Foxp3 to establish the appropriate immune response. Foxp3 swaps out these binding partners depending on the environmental cue. These environmental triggers help Foxp3 regulate TREG cell function, control immune responses, and prevent autoimmune disease, but they can also promote tumor growth. This new paradigm proposes druggable strategies to modulate TREG cell function.

“By exploring the configuration of Foxp3 protein, we hope to identify new druggable targets and design a better protein, leading to better TREG cells, meaning better treatments,” said Feng. “As immunologists, we don’t just want to understand the mechanisms; we want to know how we can take advantage of this knowledge to engineer better therapies.”

In a separate study, Benjamin Youngblood, PhD, Department of Immunology, and Caitlin Zebley, MD, PhD, Department of Bone Marrow Transplantation & Cellular Therapy, in collaboration with researchers at the University of Minnesota, discovered that T cells can proliferate indefinitely without the typical functional decline seen in most cell types. This work, published in Nature Aging, revealed that T cells can outlive an organism, potentially enduring multiple lifetimes.

To study this phenomenon, the researchers used specific biomarkers known as epigenetic markers that accumulate over time. This “epigenetic clock” tells a retrospective story about the life cycle of a cell independent of the organism itself. The accumulation of genetic mutations, the shortening of telomeres (the protective caps

on chromosomes) and methylation patterns are currently regarded as the most accurate ways to interrogate the process of aging.

Through a collaboration with investigators at the University of Minnesota, the researchers utilized a mouse model that maintained the same line of T cells through several life cycles. Based on the markers of the epigenetic clock, the researchers found that the T cells were not bound by the reasonable limits of organism lifespan, surviving for up to four lifetimes. This study underscores the pivotal role of epigenetics in T-cell aging and function, revealing how molecular mechanisms extending beyond chronological age can influence cellular memory and longevity.

Fine-tuning T cells to overcome immunotherapy challenges

Immunotherapies face challenges impacting their effectiveness, particularly maintaining functional persistence, which ultimately reduces the long-term efficacy of such treatments. When T cells

Tae Gun Kang, PhD, Department of Immunology, uses flow cytometry to research T-cell behavior and function.

are overstimulated, they become exhausted, a nonfunctional phase that significantly impairs their ability to destroy tumors. T-cell exhaustion has emerged as one of the primary reasons many T cell–based immunotherapies fail.

In a paper published in Nature Immunology, Youngblood and his colleagues identified the level of stimulation that leads to optimal anti-cancer performance. They found that preventing T-cell exhaustion requires precise stimulation. The study also revealed that how tightly a parental T cell binds to a cancer protein determines if its daughter cells will be anti-cancer effectors or exhausted. If binding strength is not just right, the progenitor T cells develop into exhausted cells.

We showed Asxl1 disruption endows T cells with superior long-term therapeutic potential, which could be a promising strategy for the design of future T cell–based immunotherapies.

Caitlin Zebley, MD, PhD Department of Bone Marrow Transplantation & Cellular Therapy

exhausted state will allow us to develop engineering approaches that improve the longevity of T cell–based immunotherapies for solid and liquid tumors.”

“We wanted to know how signal strength contributed to either the maintenance or the progression of T cells to a terminally exhausted state,” said Youngblood. “Understanding what controls the transition between progenitor to the dysfunctional

Checkpoints are signals that tell T cells how to react to diseased cells or pathogens. Tumors can hijack these checkpoints to turn off the immune system. One type of immunotherapy, immune checkpoint inhibitors, blocks tumors’ ability to suppress T-cell function, thereby helping the immune system find and kill cancer cells.

Although the approach has shown remarkable success, it does not

work for all patients. To understand why, Zebley and Youngblood collaborated with colleagues at the Van Andel Institute. The researchers explored what is different about the T cells of patients who respond to immune checkpoint inhibitors.

“Looking at clinical trial data from myelodysplastic syndrome patients treated with checkpoint inhibitors, we saw that while most didn’t respond well, a small subset had long-term survival,” explained Zebley. “These patients had an ASXL1 mutation in the T cells, which led us to question whether the mutation could drive response to immune checkpoint inhibition.”

Advanced technology automates the loading of microarrays, enabling high-throughput analysis for cutting-edge research.

A microarray slide hybridized with fluorescent probes to detect the expression of specific molecules across various samples.

Our research efforts defining barriers limiting immunotherapy will guide our future efforts to engineer more effective treatments and grow our pediatric immuneoncology program.

Benjamin Youngblood, PhD Department of Immunology

In a paper published in Science, the researchers reported that intentional Asxl1 disruption in murine T cells improves tumor control during immune checkpoint inhibition. The investigators also discovered that Asxl1 regulates the epigenetic checkpoint governing terminal T-cell differentiation into the exhausted state. Asxl1-depleted T cells resisted exhaustion for the animal’s lifespan and controlled a range of tumors, compared to T cells with Asxl1 intact, which become exhausted and control only a limited type of tumors.

“We showed Asxl1 disruption endows T cells with superior longterm therapeutic potential, which

could be a promising strategy for the design of future T cell–based immunotherapies,” Zebley said.

Orchestrating breakthroughs in bone marrow transplantation

Breakthroughs in understanding fundamental T-cell biology pave the way for more precise and effective immunotherapies. “Support for fundamental science is one of the many things that makes St. Jude special,” explained Youngblood. “Our research efforts defining barriers limiting immunotherapy will guide our future efforts to engineer more effective treatments and grow our pediatric immune-oncology program.”

An example of how fundamental insights lead to tangible improvements is findings from a phase 2 clinical trial published in the Journal of Hematology & Oncology. The study, led by Brandon Triplett, MD, and Swati Naik, MBBS, both of the Department of Bone Marrow Transplantation & Cellular Therapy, shows promise in enhancing the donor immune attack on the host’s leukemic cells, called the graft-versus-leukemia effect, without causing excessive dangerous graft-versus-host disease (GVHD).

Patients with leukemia or other blood cancers who do not respond to chemotherapy often need hematopoietic cell transplantation, also called bone marrow or stem cell transplantation, to treat their cancer. Although potentially lifesaving, transplantation carries substantial risks.

from the donor’s bone marrow identify the patient’s tissues as foreign and launch a harmful immune attack. The researchers minimized this complication by selectively removing naïve T cells, which are defined as T cells that have not yet encountered the specific protein they were designed to recognize and which generally drive GVHD. By targeting only naïve T cells, the researchers could leave mature memory T cells behind. These memory T cells harness the beneficial graftversus-leukemia effect and can protect patients against infections while minimizing the risk of GVHD.

In this study, even without total body irradiation, the leukemia-free survival rates were comparable, if not better, than those seen in studies that used it.

Swati Naik, MBBS Department of Bone Marrow Transplantation & Cellular Therapy

A scientist analyzes fluorescent signals on a microarray to gain insights into molecular activity in ongoing research.

We’re designing [the immune system] to be as robust as possible against infections and leukemia while carefully minimizing the risk of graftversus-host disease.

Brandon Triplett, MD

Department of

Bone Marrow Transplantation & Cellular Therapy

“In bone marrow transplantation, total body irradiation is typically considered essential to achieve favorable outcomes,” explained Naik. “However, in this study, even without total body irradiation, the leukemia-free survival rates were comparable, if not better, than those seen in studies that used it.”

“The thing about transplantation is that you’re building a whole new immune system in the recipient from the donor cells,” added Triplett. “We’re designing it to be as robust as possible against infections and leukemia while carefully minimizing the risk of graft-versus-host disease.”

As scientists deepen their understanding of T-cell biology and immune system activity, breakthroughs advance the development of finetuned and effective therapies. By enhancing the power of T cells and other immune components, St. Jude researchers are laying the foundation to improve immunotherapy treatment for patients with even the most intractable cancers.

Clinical trials usher in a new era of pediatric HIV treatment

For four decades, the HIV and Translational Medicine Program at St. Jude has advanced treatment and prevention options for children and youths living with and striving to prevent HIV.

Yet from initial treatments, which required taking multiple pills several times a day, to one pill daily, to two intramuscular injections given once every two months, St. Jude has played a role in the progress that has transformed HIV from a life-threatening disease into a manageable chronic condition.

Research that provides new treatment options for younger populations

St. Jude has helped accelerate the U.S. Food and Drug Administration (FDA) and Canada Health approval timeline for the combined administration of the

long-acting injectable antiretrovirals cabotegravir and rilpivirine in adolescents (aged 12 to 18 years). The approach was tested through the phase 1/2 International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network clinical trial co-led by Aditya Gaur, MD, Division of HIV and Translational Medicine director and Department of Infectious Diseases, and his colleague Carolyn BoltonMoore at the Centre for Infectious Disease Research in Zambia, Africa.

Results from the study, also referred to as the More Options for Children and Adolescents (MOCHA) study, were published in The Lancet HIV. The study, which involved participants from 15 centers across four countries, showed positive safety, acceptability, and tolerability of this two-drug injectable regimen in youths aged 12 to 17 years.

“There will always be a little bit of lag between when promising drugs or discoveries get approved for adults versus children and youths,” said Gaur. “But for this first all-injectable HIV

Doses of long-acting injectable antiretrovirals, rilpivirine and cabotegravir, administered in combination, are the latest treatment option for youth living with HIV.

treatment regimen, approval for use for adolescents in the United States and Canada was relatively soon after the approval for adults, a credit to the IMPAACT 2017 study participants and the collaboration of the National Institutes of Health, ViiV Healthcare, and Janssen R&D, who sponsored the study.”

Expanding treatment options to even younger populations

The approval brings a new treatment option to adolescents who may struggle with adhering to a one-pill-a-day regimen, the current standard of care.

“When we think of any chronic disease, be it HIV, diabetes, or high blood pressure, people struggle with taking medicine every day,” Gaur explained. “Additionally, when you have a condition stigmatized in society, where the act of taking a pill in the presence of someone else may be a reminder that you have HIV, one can see why adhering to a simple, potent, safe one-pill-a-day combination can become even harder.”

St. Jude also participated in a pharmaceutical company–led and sponsored phase 2/3 multicenter trial

to assess the safety of co-formulated bictegravir, emtricitabine, and tenofovir alafenamide administered in single-tablet form for 48 weeks in children aged 2 years or older living with virologically suppressed HIV in South Africa, Thailand, Uganda, or the United States.

We are taking steps to achieve the goal of ending the HIV epidemic [and are] fortunate to walk alongside patients, research participants, and their families as we work toward this future.

Aditya Gaur, MD Department of Infectious Diseases

Initial results published in The Lancet HIV — the first report to assess the safety and dose of a single-tablet option in young children — found the fixed-dose combination of the three medications to be efficacious and well tolerated with good adherence. The findings supported the FDA and European Medicines Agency approval of the low-dose, single-tablet co-formulation as a treatment for HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. The use of this new formulation was also added to the recommended-use guidelines issued by the U.S. Department of Health and Human Services.

Reflecting on the importance of advancing HIV treatment options to all age groups, Gaur stated that “the HIV Program at St. Jude is committed to providing the best multidisciplinary care and access to research independent of a person’s ability to afford or access care, and we are taking steps to achieve the goal of ending the HIV epidemic in collaboration with our community partners. We are fortunate to walk alongside patients, research participants, and their families as we work toward this future.”

(Left) Members of the Infectious Disease Clinic — Kierra McCallum, RN, and Lauren Braskich, RN — prepare a new treatment option for youth living with HIV: a combination injection of long-term acting antiretrovirals cabotegravir and rilpivirine. (Right) Aditya Gaur, MD, and clinical pharmacist Susan Carr, PharmD, review single-tablet treatment options for pediatric patients living with HIV.

Every year, the breadth and depth of the research enterprise at St. Jude expands. The Scientific Highlights capture a snapshot of the diversity of fields, departments, and researchers charting new discoveries at St. Jude. These high-impact publications provide a window into the scientific accomplishments of St. Jude investigators in 2024.

scientific highlights

Discovering a molecular driver of lethal outcomes for viral respiratory disease

What drives infections to become severe, perhaps even fatal, in some individuals but not in others is an area of infectious disease research that has been difficult to study. Collaborative research between St. Jude, the Peter Doherty Institute for Infection and Immunity, Harvard University, and other institutions, published in Cell, has shed light on the problem, revealing that oleoyl-ACP-hydrolase (OLAH), an enzyme involved in fatty acid biosynthesis, is a driver of severe disease outcomes.

“It took years of working closely with basic scientists and clinicians from across the world, all studying different infections and diseases, for OLAH’s important role in the immune response to come to light,” said co-first and co-corresponding author Jeremy Chase Crawford, PhD, Department of Host-Microbe Interactions.

The lack of recognition for OLAH’s important role was due to difficulties in collecting unbiased datasets during severe disease. Because OLAH is rarely expressed, even in healthy tissue, scientists have long focused on panels of genes with presumed roles in disease. To overcome these barriers and better understand how OLAH works, the researchers assembled comprehensive datasets covering as many genes as possible from years of collaborative projects that examined multiple diseases.

Researchers turned their attention to OLAH when transcriptomic analysis of blood from hospitalized patients infected with avian A (H7N9) influenza first showed a link between the expression of OLAH — present early after hospital admission and throughout disease progression — and fatal disease.

This initial finding led Crawford to expand the datasets, examining the enzyme in different cohorts of individuals who experienced respiratory infections and in mouse models of disease.

“We generated transcriptomic datasets from several projects through years of studying distinct patient cohorts. It occurred to us to look at OLAH, and that’s how we started to see these amazing associations across different diseases,” explained Crawford, a founding member of the St. Jude Center for Infectious Diseases Research (CIDR).

While subsequent studies of patients hospitalized for seasonal influenza, SARS-CoV-2, respiratory syntactical virus, and multi-system inflammatory syndrome in children found high expression of OLAH, mouse models demonstrated that a lack of OLAH expression correlated with infections that became survivable. The explanation for why lies in how OLAH produces elevated levels of fatty acids, namely oleic acid. These findings support previous research that showed viral infections in cell lines become worse when oleic or palmitic acid levels increase.

The findings advance the understanding of respiratory viruses and have broad health implications. Not only could OLAH become an indicator of disease severity, but the knowledge that it is present shortly after symptom onset means it could be used as a biomarker to determine initial treatment responses.

“This is just the beginning of our exploration of OLAH,” Crawford said. “There is much more work to be done in infectious disease and other potential applications.”

Amanda Green, MD, Department of Infectious Diseases; Lee Ann Van De Velde; Robert Mettleman, PhD; and Jeremy Chase Crawford, PhD, Department of Host-Microbe Interactions discuss their work published in Cell

Improving long-term academic achievement through early interventions

Having and undergoing treatment for a brain tumor can impact a survivor long after concluding therapy, including reduced academic readiness. Scientists at St. Jude found that very young children treated for brain tumors were less prepared for school (measured by academic readiness scores) than their peers, emphasizing a need to intervene before they start to struggle in school.

In one of the first studies to examine academic readiness in infants and young children (less than 3 years old) after brain tumor treatment, the scientists observed an increasing gap between the patients treated for brain tumors and their same-age peers. The study, published in the Journal of the National Cancer Institute, followed a group of 70 patients who had developed brain tumors and

underwent treatment, assessing them six months after diagnosis and then annually for five years.

“Even in very young children, we found academic readiness was starting to lag behind healthy children their age,” said corresponding author Heather Conklin, PhD, Division of Neuropsychology chief and Department of Psychology & Biobehavioral Sciences member. “They were gradually falling behind their same-age peers in academic fundamentals, such as learning their letters, numbers, and colors.”

Previous research focused on schoolaged children also observed gaps in academic skills, but such gaps in younger children revealed an early and pervasive challenge. “Early academic readiness was predictive

of long-term reading and math outcomes,” said Conklin. “These children don’t catch up naturally.”

To address these concerns, the team proposed early intervention before a child enters elementary school. “We now know that we don’t need to wait until patients are struggling with math and reading; we can intervene earlier,” said Conklin. “We showed that the variability we’re seeing early on predicts long-term academic skills, which highly suggests earlier interventions will be beneficial and make a real difference.”

However, the researchers recognized that it was not enough to implement early interventions without first understanding what increased young learner’s vulnerability to or protected against the academic readiness gap. They examined myriad potential factors involved, such as treatment type and demographics, and found one standout determinant.

“The only clinical or demographic factor we found that predicted academic readiness was socioeconomic status,” explained Conklin. “Being from a family of higher socioeconomic status had a protective effect on children’s academic readiness.”

The finding that higher socioeconomic status is partially protective suggests that investing in resources to replace lost early enrichment experiences can mitigate the readiness gap. By increasing access to those opportunities, more children could be protected.

“Our results suggest that families can make playtime meaningful,” Conklin said. “By making small changes in how they interact with their child, with the support of their medical team and receiving appropriate resources, they can make a difference in their child’s cognitive and academic outcomes.”

In a study published in the Journal of the National Cancer Institute, Heather Conklin, PhD, Department of Psychology & Biobehavioral Sciences, explores the myriad factors impacting academic readiness for young children.

scientific highlights

A breakthrough in battling resistance with nextgeneration antibiotics

Mycobacterium abscessus (Mab) infections are becoming increasingly common in health care settings. Such infections can be hazardous for patients with compromised lung function, such as in cystic fibrosis, or who are immunologically compromised, such as in childhood cancer. These infections are treated with long courses of antibiotics and can result in poor outcomes. The emergence of Mab and other similar pathogens presents a growing and deeply concerning public health threat because there are few effective therapeutic options and a limited drug development pipeline.

When treating Mab, clinicians have a limited number of effective antimicrobials from which to choose. However, resistance has emerged to these drugs, limiting the available treatment options and leaving very few viable alternatives.

Furthermore, this naturally antibioticresistant pathogen is becoming more prevalent, highlighting the urgent need for novel therapeutics.

“We chemists are in a race against the pathogens. We make stronger antibiotics, and the pathogens become more resistant,” said Richard Lee, PhD, Department of Chemical Biology & Therapeutics.

Scientists at St. Jude are tackling Mab antibiotic resistance, designing new versions of the drug spectinomycin that overcome resistance mechanisms. In the study, published in Proceedings of the National Academy of Science, the researchers modified the naturally occurring antibiotic spectinomycin to create analogs, comparable but structurally distinct N-ethylene linked aminomethyl spectinomycins (eAmSPCs).

These synthetically created eAmSPCs are up to 64 times more potent against Mab than standard spectinomycin.

The scientists unraveled the mechanism of action by which eAmSPCs are more effective: They circumvent efflux. Efflux is the process that cells use to eliminate a drug — imagine pumping water out of a flooded basement— and is a significant mechanism by which cells become resistant to therapy. Cells use specific drug efflux pumps to expel drugs.

The N-ethylene linkage structure of the eAmSPCs plays a critical role in how the compounds avoid efflux, suggesting that longer linkages modify how the compound is pumped out of the cell. This ultimately shifts the balance toward higher concentrations of eAmSPC within the cell and thus enhances antimicrobial efficacy.

“By re-engineering the molecule through structure-based drug design, we and our collaborators have adapted the antibiotic to increase its activity,” Lee added.

The researchers also found that eAmSPCs work well with various antibiotic classes used to treat Mab and retain their activity against other mycobacterial strains. Collectively, this work demonstrates that eAmSPCs should be further studied and developed. Once issues of tolerability and safety are addressed, these compounds could become next-generation therapeutics.

“Over the past two decades, we’ve seen a massive increase in infections caused by nontuberculous mycobacteria like Mab,” said co-first author Gregory Phelps, PharmD, Graduate School of Biomedical Sciences. “If we can boost the drug pipeline against these hardto-treat bacteria, we can potentially make a difference for patients like the ones we have here at St. Jude who are increasingly faced with limited or no therapeutic options.”

Richard Lee, PhD (left); Suresh Dharuman, PhD (center), St. Jude Department of Chemical Biology & Therapeutics; and Gregory Phelps, PharmD, of the Graduate School of Biomedical Sciences (right), conducted research to develop powerful new antibiotics to address antibiotic resistance in Mycobacterium abscessus.

A blueprint for translating genome-editing strategies to clinical trials

Treatments for sickle cell disease, a genetic blood disorder associated with chronic anemia, severe pain crises, progressive multiorgan damage, and early mortality, have limitations because currently approved drugs, such as hydroxyurea, are only partially effective. Allogenic bone marrow transplantation is potentially curative but is associated with immune toxicities, such as graftversus-host disease and graft rejection. Matched donors for the procedure are also limited; less than 20% of patients with sickle cell disease find a match. Genome editing of patients’ stem cells could circumvent these challenges.

Published in Molecular Therapy, St. Jude scientists detailed the safety and efficacy of a gene editing approach that induces fetal hemoglobin. Hemoglobin is a red blood cell protein that carries oxygen throughout the body.

Sickle cell disease affects this protein, but fetal hemoglobin (present before birth) offers an alternative. By editing blood stem cells to express fetal hemoglobin, researchers may be able to treat sickle cell disease.

The approach, initially developed in the lab of co-corresponding author Mitchell Weiss, MD, PhD, Department of Hematology chair, uses a CRISPRCas9 genome editor programmed to make targeted DNA double-stranded breaks. The researchers used this editor to interfere with the target of a repressor protein called BCL11A, which ceases fetal hemoglobin expression in adult blood cells.

“We compared different possible editing targets and identified a lead target that was not only highly effective at inducing fetal hemoglobin but also highly specific,”

said co-corresponding author Shengdar Tsai, PhD, Department of Hematology. “To understand where Cas9 was acting in the edited cells’ genome, we used an approach my lab developed called CHANGE-seq; it selectively sequences DNA modified by genome editors.”

The lab of co-corresponding author Jonathan Yen, PhD, Department of Hematology, optimized the cellediting process at the clinical scale by collaborating with the Children’s GMP, LLC. They demonstrated they could edit cells at the quantity and quality required to treat patients in a clinical trial.

Preclinical studies showed that Cas9 editing at the targeted binding site induced fetal hemoglobin to levels predicted to be therapeutically effective with no detectable offtarget effects in the edited human hematopoietic stem cells. These results prompted the team to open the first genome editing clinical trial at St. Jude, called St. Jude Autologous Genome Edited Stem Cells (SAGES-1).

In addition to providing the foundation for future St. Jude studies, this work supplies a blueprint for other researchers. “We described the complete story of developing a genome editing strategy to treat sickle cell disease from preclinical studies to scaling up the editing process to clinical readiness and understanding of safety and potential toxicities,” said Tsai. “By publishing these studies, we hope to help other groups by providing an example of studies required to clear an investigational new drug application.”

The team anticipates this study will be the first of a series of advances in genome editing medicines at St. Jude. They hope to catalyze similar efforts both at St. Jude and elsewhere.

Co-corresponding authors Shengdar Tsai, PhD; Mitchell Weiss, MD, PhD; and Jonathan Yen, PhD, all of the Department of Hematology, explored using a CRISPR-Cas9 approach to treat sickle cell disease in a study published in Molecular Therapy

scientific highlights

Characterizing approaches to treatment decision-making for children presenting with advanced cancer in resource-limited settings

More than 80% of children who receive cancer treatment in countries with significant resources survive their illness. At diagnosis, the provision of cure-directed therapy is considered the norm for most of these children. However, the global burden of pediatric cancer is not distributed equitably. Approximately 90% of children diagnosed with cancer live in resourcelimited countries. Children presenting with advanced cancer are particularly vulnerable, as many face barriers to accessing the health care they need, resulting in adverse outcomes.

In a study published in Supportive Care in Cancer, St. Jude researchers investigated approaches to clinical decision-making for children presenting with advanced cancer in resource-limited countries. “We identified a research gap. We had a poor understanding of how physicians

approach decision-making for these children and recognized the importance of using qualitative research methods to explore this topic. This was a key first step toward designing interventions to improve patient outcomes and clinician workflows,” said first author Marta Salek, MD, MPH, Department of Global Pediatric Medicine.

Eleven participants from the St. Jude Global Alliance community, representing each World Health Organization–designated region, were invited to participate in focus groups. As experts in pediatric oncology, the group offered unique insights into their treatment decision-making processes within their local contexts.

“We asked participants to brainstorm factors that influence their treatment decision-making for a child presenting with advanced cancer at diagnosis,

which were then reviewed and debated,” Salek explained. “This was followed by discussions regarding whether physicians considered treatment with noncurative intent for these children at diagnosis, including when it could or could not be appropriate. We also asked them to reflect on local definitions of ‘poorprognosis cancer’ at diagnosis.”

The focus groups identified many multi-level health system factors involved in decision-making, including family preferences, available resources, family health care access, local culture, and national payment structures for delivering childhood cancer therapy. These results illustrated that participants experienced difficulties with complex decision-making at diagnosis. Furthermore, the data suggested these challenges may be magnified by diverse factors underrepresented in existing decisionmaking frameworks or childhood cancer treatment guidelines. Inconsistent definitions of a “poor prognosis” amplified these difficulties.

Salek and her team plan to explore treatment decision-making in greater depth by leveraging diverse perspectives from patients, families, and multidisciplinary clinicians. With this qualitative research, they aim to develop pragmatic strategies to support treatment decision-making in resource-limited settings adaptable to local contexts and empower physicians to offer the best available treatment options. In instances when curative-intent treatment at diagnosis is not possible, such insights could highlight areas within health systems that need strengthening.

Improving outcomes for children diagnosed with cancer regardless of where they live is at the heart of this work. “We want to ensure that, in the future, all children presenting with cancer can be offered treatment with curative intent safely,” said Salek.

In a study published in Supportive Care in Cancer, first author Marta Salek, MD, MPH, Department of Global Pediatric Medicine, examined the complex factors that influence decision-making at the time of a childhood cancer diagnosis, highlighting the challenges in existing frameworks.

Solving the decades-long mystery of NLRC5 sensor function in inflammation and disease

Innate immune sensors are an integral part of the immune system, acting as a first line of defense to protect against disease and infection. Activated sensors trigger a cascade of events that can be beneficial and provide host defense but can also cause inflammation and disease.

As part of their response, innate immune sensors assemble complexes that integrate signals and respond to threats. One such complex is the PANoptosome, which drives a prominent inflammatory cell death type called PANoptosis. However, how specific innate immune sensors work and what triggers them to act have remained mysterious for decades.

Chipping away at the mystery, scientists at St. Jude, led by ThirumalaDevi Kanneganti, PhD, Center of Excellence for Innate Immunity and Inflammation director and Department of Immunology vice chair, published research in Cell showing how a member of the nucleotide-binding

oligomerization domain-like receptor (NLR) family, NLRC5, plays a previously unidentified role driving PANoptosis.

To understand its role in disease and elucidate the triggers of NLRC5, the scientists screened combinations of immune-system threats, including pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and cytokines (immune signaling molecules) that can be released by or mimic an infection, injury, or illness. This comprehensive approach is built on extensive research that has shown the multifaceted nature of innate immunity; this contrasts with the conventional single ligand-receptor model of study, which has historically oversimplified the complex interplay of innate immune signaling.

Through this process, the researchers examined heme, a hemoglobin component that binds oxygen to carry the molecule throughout the body. However, “free heme”

can also be released when red blood cells rupture, leading to inflammation and organ damage.

“We identified that the combination of heme plus PAMPs or cytokines specifically induces NLRC5-dependent PANoptosis,” said co-first author Balamurugan Sundaram, PhD, Department of Immunology. “This showed for the first time that NLRC5 is central in responding to hemolysis, which can occur during infections, inflammatory diseases, and cancers.”

The results led the team to investigate how NLRC5 is regulated. They found that depletion of a key molecule for cellular energy production — nicotinamide adenine dinucleotide (NAD) — signals to the immune system that there is a threat, driving NLRC5 protein expression.

“Supplementing with the NAD precursor, nicotinamide, blocked NLRC5-mediated PANoptosis,” said co-first author Nagakannan Pandian, PhD, Department of Immunology. “Therapeutically, nicotinamide has been used as a nutrient supplement, and our findings suggest it could help treat inflammatory diseases.”

With this knowledge, the team searched for how NLRC5 could be a target in therapeutic approaches to mitigate PANoptosis associated with diseases. They found that deleting Nlrc5 protected against inflammatory cell death and prevented disease pathology in hemolytic and inflammatory disease models, making NLRC5 an exciting therapeutic prospect.

“The concepts of PANoptosomes and PANoptosis are fundamental to our understanding of how innate immune sensing works and can be translated to numerous diseases and conditions,” said Kanneganti. “For conditions with no targeted therapies — inflammatory disorders, infectious disease, cancers, aging — targeting PANoptosis could be an option.”

Thirumala-Devi Kanneganti, PhD; Balamurugan Sundaram, PhD; and Nagakannan Pandian, PhD, Department of Immunology, published research revealing the function of the innate immune sensor NLRC5 in cell death.

scientific highlights

Epigenetic insights help reveal the causes of unsolved epileptic neurological disorders

To effectively treat a disease or disorder, doctors must first know the root cause. Such is the case for developmental and epileptic encephalopathies (DEEs), whose root causes can be complex and heterogeneous. DEEs affect 1 in 590 children in the United States each year and involve more than 825 genes.

When a child is diagnosed with DEE, linking the encephalopathy to a specific gene can help facilitate appropriate treatment or symptom control. However, current testing methods can clinically identify the root cause, or etiology, of only 50% of individuals’ DEEs. Unfortunately, the remaining half of patients’ encephalopathy remains unexplained.

Addressing the genetic root causes for DEEs has been a long-term goal for Heather Mefford, MD, PhD, Pediatric Translational Neuroscience Initiative

and Department of Cell & Molecular Biology. Mefford was instrumental in raising the number of diagnosable cases to 50%, up from approximately 5% just a decade ago.

Today, 80% of identifiable DEEs can be explained by 27 genes. To tackle the remaining unsolved cases, the numerous rare occurrences of these disorders must be identified, a challenge that Mefford and her team embrace. The team is exploring epigenetics, the changes in gene expression, as a potential solution. One such epigenetic change involves a process called DNA methylation. This process regulates gene expression by adding a methyl group to a gene’s promoter region, which prevents transcription factors from binding to the DNA, ultimately leading to gene silencing or reduced expression.

In a study published in Nature Communications, Mefford and her team demonstrated that DNA methylation patterns can help identify the cause of DEEs. Their findings highlight how specific gene and genome-wide methylation “epi-signatures” can help pinpoint genes responsible for the disorder.

“For some genetic disorders, everyone with a mutation in the same gene has a methylation profile across their genome that puts them in a category with all the others with the same genetic disorder,” said Mefford. This methylation landscape is called an “epi-signature” and is akin to a DEE fingerprint.

While epi-signatures allowed the researchers to broadly identify DEEcausing variants, taking a closer look at the individual methylation instances, referred to as rare differential methylation analyses, revealed further insights. “The underlying cause of the disease manifests in an epi-signature that can serve as a marker for that gene,” explained cofirst author and Graduate School of Biomedical Sciences student Christy LaFlamme. “With rare methylation events, their analysis can point directly to the cause of the disease.”

Exploring these rare methylation events across the genome using longread DNA sequencing pointed the researchers toward DNA regions that are not commonly assessed, offering an answer to the cause of some cases. This allowed the researchers to identify the causative and candidate etiologies of DEEs in 2% of previously unidentified cases. This research represents another significant step in identifying rare instances of DEEs and another tool to aid in diagnosing children with DEEs.

Heather Mefford, MD, PhD, Department of Cell & Molecular Biology (right), and Christy LaFlamme, St. Jude Graduate School of Biomedical Sciences (left), used DNA methylation patterns to identify the causes of previously unexplained developmental and epileptic encephalopathies (DEEs), offering new hope for diagnosing rare cases.

Discoveries are ‘one click’ away with the St. Jude survivorship portal

The population of pediatric cancer survivors is growing — around 85% of childhood cancer patients survive to five years post-diagnosis in the U.S., with most living decades beyond that. But with more survivors comes more people at risk of adverse health effects caused by cancer or their cancer treatment.

Researchers are studying childhood cancer survivors to learn how to tailor improved therapies, provide screening, and support patients later in life. However, this research hinges on access and the ability to analyze collected comprehensive survivorship data systematically. In a boon to such studies, scientists at St. Jude created the St. Jude Survivorship Portal, the first data portal of its kind dedicated to sharing, analyzing, and visualizing cancer survivorship data — all open

access and free to use as part of the St. Jude Cloud ecosystem.

Poised to offer significant contributions to survivorship research thanks to its two large survivorship cohorts, the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort (St. Jude LIFE), St. Jude already possessed a rich data source for investigators to mine new survivorship insights. The creation of the survivorship portal serves as a tool that leverages this wealth of data and offers a resource that has the potential to propel the field of survivorship research forward.

“We aren’t just sharing data,” said cocorresponding author Yutaka Yasui, PhD, Department of Epidemiology & Cancer Control. “We are facilitating the analysis and visualization of data and making it free to anyone —

that’s a tremendous resource for the cancer survivorship community.”

Published in Cancer Discovery, scientists at St. Jude unveiled the big-data platform incorporating clinical and genomic information. The unprecedented research system integrates three sets of data: whole genomic sequencing, treatment exposure, and outcomes, in which there are 1,600 phenotypic variables and 400 million genetic variants from over 7,700 childhood cancer survivors.

Maintaining such an expansive data platform is a commitment the St. Jude team willingly assumes, ensuring access to a vast resource is sustained.

“Continued enhancement of the portal architecture is key to enabling on-the-fly analysis, which integrates data on treatment exposures, whole genome sequencing, and long-term outcomes,” said co-corresponding author Xin Zhou, PhD, Department of Computational Biology. “There are half a billion clinical data points in the portal and hundreds of terabytes of genetic data supported by dynamic and interactive visualization analysis.”

Among the various use cases that served to illustrate the discovery potential of the portal, the research team highlights their comparison of associated outcomes for two types of platinum chemotherapies, cisplatin and carboplatin, reaffirming that cisplatin is associated with greater auditory toxicity than carboplatin.

“By enabling the study of the mechanisms underlying toxicity, the portal can inform investigators how to prioritize drugs for treatment,” said cocorresponding author Jinghui Zhang, PhD, Department of Computational Biology. “Investigators can come to the portal with different interests, genetics, drug usage and exposure, or survivorship — these perspectives can all be explored in the portal.”

Jinghui Zhang, PhD, Department of Computational Biology; Yutaka Yasui, PhD, Department of Epidemiology & Cancer Control; and Xin Zhou, PhD, Department of Computational Biology, unveiled the St. Jude Survivorship Portal in Cancer Discovery.

scientific highlights

‘Molecular putty’ properties of biomolecular condensates coded in protein sequence

Within cells lie membraneless hubs of concentrated proteins and nucleic acids called biomolecular condensates. Like liquid droplets, these condensates are centers of reaction for the spatial organization of biomolecules. Beyond cellular organization, these condensates play roles in disease, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.

Understanding how these reaction hubs function and change over time is key to better understanding the mechanisms that drive disease. Studies of biomolecular condensates have uncovered layers of complexity, including their changing material properties, known as “aging.” In these aging processes, the condensates change from having viscoelasticliquid properties into a viscoelastic solid over time. To better understand

these changing material properties, St. Jude scientists, in collaboration with the State University of New York at Buffalo and Washington University at St. Louis, studied the interaction networks within condensates to better understand the rules associated with their unique material properties. The study was published in Nature Physics

“Condensates have often been described as liquid-like, but their material properties can vary quite a bit,” says co-corresponding author Tanja Mittag, PhD, Department of Structural Biology. “That depends on the sequences of the proteins within them and the lifetime of the interactions being formed.”

Mittag leads an effort to understand how the amino acid sequence of proteins that form these biomolecular condensates determine these material

properties through the St. Jude Research Collaborative on the Biology and Biophysics of RNP Granules. Previous work published in Science established a “stickers-and-spacers” model for predicting phase separation behavior in proteins. “Stickers” are amino acids that connect with other stickers, while “spacers” are amino acids necessary for the arrangement of stickers and interactions with water.

Building upon this “sticker-and-spacers” model, the researchers found that the material behavior of biomolecular condensates depends on the strength of these sticker–sticker interactions.

“What we call ‘sticker’ amino acids make pairwise interactions that form a network fluid,” Mittag said. “Now, we understand that these pairwise contacts that are forming — how stable they are and what their lifetime is — determine the condensates’ viscoelastic properties, and we can push their behavior toward elastic properties if we make stronger interactions. We now understand the protein sequence encodes this.”

The team’s work further explored how condensates age, identifying a new path in aging by building on the “stickers-and-spacers” model.

“If we exchanged spacer amino acids for ones that like to interact more with water, we could get condensates to age into a viscoelastic solid,” says co-first author Wade Borcherds, PhD, Department of Structural Biology. “This is like putty becoming a rubber ball. They can both bounce, but one is solid, and one is not.”

Now that the scientists understand how the aging process is encoded in the protein sequence, they can test whether this is the basis for certain neurodegenerative diseases’ development.

Tanja Mittag, PhD, and Wade Borcherds, PhD, Department of Structural Biology, studied the interaction networks within biomolecular condensates to better understand and define these unique material properties.

design to enhance CAR T–cell therapy for leukemia in a study published in Cell Reports Medicine

Scientists combine novel CAR design and AI to improve CAR T–cell immunotherapy

Chimeric antigen receptor (CAR) T–cell therapy redirects a patient’s own immune cells to target a cancerspecific protein. Optimizing CAR T–cell therapy for different pediatric cancers requires an improved understanding of T–cell biology and immune processes. One challenge in the field has been identifying tumor-specific targets that are both uniformly expressed and not essential in healthy tissues. St. Jude scientists are addressing this issue by designing and developing CARs with more sophisticated targeting abilities. The work provides a foundational understanding that may guide future CAR T–cell design across cancer types.

The study, published in Cell Reports Medicine, showed how a computational approach incorporating AlphaFold2,

an AI-powered protein folding prediction tool, could shed light on how structure impacts CAR T–cell function in acute myeloid leukemia (AML). Combining this improved CAR design with computational prediction could potentially expand treatment options for AML and other malignancies traditionally resistant to current therapies.

“One of the most exciting aspects of the approach is that although we focused on leukemia, it can be widely extrapolated to other tumors such as solid and brain tumors,” said senior corresponding author Paulina Velasquez, MD, Department of Bone Marrow Transplantation & Cellular Therapy.

The researchers created a unique single-molecule CAR, which includes the region of an antibody that binds a specific target (its antigen) and one short peptide that binds a separate target. These two binding domains are connected by a linker, enabling the CAR to target two different cancer-related proteins.

This approach overcomes inefficiencies in CAR T–cell therapy caused by the inability to target large antibody fragments. “Our approach added a small peptide, enabling our CAR to engage either target to prevent immune escape,” said first author Jaquelyn Zoine, PhD, Department of Bone Marrow Transplantation & Cellular Therapy.

The dual-targeted CARs outperformed single-targeted CARs in both in vitro and in vivo experiments, demonstrating their promise. However, the researchers struggled to determine the optimal linkers to use between the binding domains. The physical structure of the targeted molecule and its linker can interfere with target binding on the cancer cell, so identifying the most effective linker could further improve the therapy.

Using computational structure prediction and comparing structures with experimental results, the researchers found that shorter, more flexible linkers improve binding and efficacy. “A linker of sufficient flexibility and shorter length can scan a larger volume and is more likely to find the target proteins on the cancer cell,” said co-author M. Madan Babu, PhD, FRS, Chief Data Scientist and Senior Vice President for Data Science.

As one of the few groups in the world employing AI-based structure prediction tools for CAR T–cell design, the researchers hope their method will encourage others to improve CAR designs and enhance treatments for pediatric cancers.

(L to R) First author Jaquelyn Zoine, PhD; senior corresponding author Paulina Velasquez, MD, St. Jude Department of Bone Marrow Transplantation & Cellular Therapy; co-author M. Madan Babu, PhD, FRS, Department of Structural Biology; and second author Kalyan Immadisetty, Department of Bone Marrow Transplantation & Cellular Therapy used AI-powered protein prediction and a dual-target CAR

scientific highlights

Switching gears in glutamine metabolism is key to red blood cell development and disease

During mature red blood cell formation, a process called erythropoiesis, blood stem cells develop through many different stages. This fundamental biological process includes complex metabolic pathways, which are often dysregulated in blood disorders such as sickle cell disease and β-thalassemia. However, these metabolic pathways and how their dysfunction contributes to disease are not fully understood.

A collaborative research team led by Jian Xu, PhD, Department of Pathology and Center of Excellence for Leukemia Studies, and Min Ni, PhD, Department of Oncology, set out to understand the metabolic pathways regulating normal red blood cell maturation and how this might be altered in various disorders.

The scientists systematically profiled metabolic changes through each red blood cell maturation stage and identified a previously unrecognized role for the amino acid glutamine.

The work, published in Science, reveals modulating glutamine metabolism is a potential therapeutic route for common red blood cell disorders. It may also serve as a tool for evaluating therapeutic efficacy.

Early blood cell maturation processes break down glutamine as an energy source, but the researchers made a surprising finding about the amino acid’s metabolism in the later stages of development. “We found this process is completely reversed during later differentiation. The cells stop breaking down glutamine and begin synthesizing it by completely reversing the reaction,” Xu explained.

Heme is the main component of hemoglobin, the protein in red blood cells that carries oxygen. Red blood cell maturation depends on heme production, but ammonium (a heme production byproduct) can accumulate if not removed, causing oxidative stress.

The researchers found red blood cells begin producing glutamine synthetase to facilitate ammonium’s removal by combining glutamate with the ammonium to produce glutamine.

Through conditional inactivation of glutamine synthetase, the researchers identified a direct link between disruption of glutamine metabolism and red blood cell disorders, such as β-thalassemia. This link causes a metabolic phenotype resembling a glutamine synthetase deficiency, characterized by increased glutamate and ammonia levels and decreased glutamine levels. They identified glutamine synthetase oxidation as the cause of this metabolic phenotype in β-thalassemia and were able to treat the condition by restoring enzyme activity.

The link between glutamine synthase deficiency and other red blood cell disorders in which the enzyme is inactivated is further supported by a recent report describing a selective impairment of erythropoiesis in a human patient with inherited glutamine synthetase deficiency, an ultra-rare inborn error of metabolism.

The researchers carried their study further, investigating how the drug luspatercept, currently used to treat β-thalassemia, works. They found the drug likely acts to restore glutamine levels. Similarly, the study suggests that the mechanisms behind other red blood cell disorder treatments, such as L-glutamine supplementation to alleviate sickle cell disease symptoms, likely involve fixing defective glutamine metabolism.

Beyond its direct impact on treating red blood cell disorders, the findings suggest metabolic features, such as glutamine-to-glutamate ratios, can be used as biomarkers for these conditions, offering a means to diagnose, monitor disease progression and evaluate therapeutic efficacy.

Co-corresponding authors Jian Xu, PhD, (left) and Min Ni, PhD, (right) and co-first authors Junhua Lyu, PhD, (center left) and Yuannyu Zhang, PhD, (center right) identified and characterized a previously unrecognized fundamental role for glutamine in blood cell development, offering new insight into blood disorders like sickle cell disease and β-thalassemia.

Comprehensive Cancer Center

Comprising five research programs and 10 shared resources, the Comprehensive Cancer Center is designed to foster interdisciplinary basic and translational research, clinical trials, and population science focused on childhood cancer and survivorship.

The National Cancer Institute (NCI) supports 72 Cancer Centers in the United States. The St. Jude Comprehensive Cancer Center, under the direction of Charles W.M. Roberts, MD, PhD, is the first and only NCI-designated Comprehensive Cancer Center solely focused on pediatric cancer.

CANCER BIOLOGY PROGRAM

co-led by: Douglas Green, PhD; Richard Kriwacki, PhD

The diverse nature of pediatric cancers, coupled with the complex molecular, genetic, and developmental contexts in which they form, necessitates a broad spectrum of discovery research to build a strong foundation for translational studies. This program aims to explore and understand the cell and molecular biology of cancer at a fundamental level. In working toward this goal, program members lead integrated and transdisciplinary efforts to define pathways related to cancer, identify genomic and epigenetic drivers of cancer, explore key cellular processes underlying cancer maintenance and progression, understand the cancer immune microenvironment, and facilitate the translation of discoveries.

CANCER CONTROL & SURVIVORSHIP PROGRAM

co-led by: Gregory Armstrong, MD, MSC; Kristen Ness, PT, PhD, FAPTA

As treatments for childhood cancers improve, the number of long-term survivors of childhood cancer increases.

This multidisciplinary program aims to conduct innovative clinical, genetic, and observational research and translate the findings into effective strategies to avert or mitigate treatment-related complications and improve the quality of life of childhood cancer survivors. Leading two of the world’s largest pediatric survivorship research studies, the St. Jude Lifetime Cohort Study and the Childhood Cancer Survivor Study, program members have influenced the design of contemporary pediatric cancer treatment strategies and provided critical data to guide health surveillance and health-preserving interventions for long-term survivors.

DEVELOPMENTAL BIOLOGY & SOLID TUMOR PROGRAM

co-led by: Michael Dyer, PhD; Alberto Pappo, MD

Some of the most devastating and poorly understood cancers that affect children and adolescents arise in the peripheral nervous system, muscles, and bones. This program aims to improve the survival and quality of life of children with solid tumors by integrating basic and clinical research. Clonal selection

contributes to disease recurrence, so this program is targeting rare tumor cell populations that survive treatment via three key areas: precision medicine, cancer immunotherapy, and translational research. Research extends from basic mechanistic development studies to therapeutic studies in preclinical models, ultimately translating these discoveries to the clinic and altering the standard of care.

HEMATOLOGICAL MALIGNANCIES PROGRAM

co-led by: Charles Mullighan, MBBS(Hons), MSc, MD; Ching-Hon Pui, MD

The program’s overall goal is to improve cure rates for hematological malignancies while minimizing therapy-related toxicity. This established, highly interactive, transdisciplinary program has a long track record of significant discoveries in cancer biology. Translation of these findings into new diagnostic and treatment approaches has changed the standard of care for children with hematological malignancies. Program members have pioneered efforts to transform childhood acute lymphoblastic leukemia (ALL) into a curable condition and defined many subtypes of ALL and acute myeloid leukemia with profound practicechanging implications now incorporated into the International Consensus and World Health Organization classifications of ALL, ultimately driving global advances in cancer research.

NEUROBIOLOGY & BRAIN TUMOR PROGRAM

co-led by: Suzanne Baker, PhD; Giles Robinson, MD

Brain tumors are the leading cause of cancer-related death in children. The goal of the Neurobiology &

Brain Tumor Program is to improve the survival and morbidity of children with brain tumors by developing the most effective, least toxic therapies through a better understanding of disease pathogenesis and normal brain development. Program members have illuminated mechanisms of oncogenesis and developmental origins of pediatric brain tumors, altered diagnostic practice worldwide by identifying refined molecular subgroups that are now incorporated into the new World Health Organization tumor classification guidelines, developed innovative clinical trials with risk-stratified design or immunotherapy approaches, and identified mitigating approaches to neurocognitive and long-term effects of therapy.

Senior Leadership

Charles W.M. Roberts, MD, PhD Director

Charles Mullighan, MBBS(Hons), MSc, MD Senior Deputy Director of Strategic Initiatives

Suzanne Baker, PhD Deputy Director of Strategic Initiatives

Hongbo Chi, PhD Associate Director, Basic Research

Heather Brandt, PhD Co-Associate Director, Outreach

Elizabeth Fox, MD, MS Associate Director, Clinical Research

Melissa Hudson, MD Associate Director, Population Sciences

Julie Park, MD

Associate Director, Translational Research

Shondra Pruett-Miller, PhD Associate Director, Shared Resources

Carlos Rodriguez-Galindo, MD Co-Associate Director, Outreach

Shared resources include: Bioinformatics and Biotechnology, Biostatistics, Cell and Tissue Imaging, Center for Advanced Genome Engineering, Center for Spatial Omics, Center for Translational Pharmacology, Flow Cytometry and Cell Sorting, Genetically Engineered Mouse Models, and Viral Vector Technology

Carolyn Russo, MD Associate Director

Dana Wallace, MS

Associate Director, Administration

Gerard Zambetti, PhD

Associate Director, Education & Training

St. Jude Affiliate Program

Providing pediatric patients with cancer or blood diseases equal access to care, regardless of their geographic location, is a central goal of the Affiliate Program. The affiliate clinics support participant recruitment for clinical trials and the geographic extension of St. Jude clinical care.

Carolyn Russo, MD, medical director of the Affiliate Program, led a task force with leaders from the Strategic Planning, Affiliate Program, Clinical Operations, and Legal Services teams to determine how the hospital’s eight affiliate clinics across the country could better meet the needs of patients residing in those areas.

As of November 1, 2024, the clinic in Huntsville dropped the “affiliate” name and is now a St. Jude clinic in Huntsville, the first St. Jude satellite clinic. The new arrangement provides a closer alignment with St. Jude in Memphis. The St. Jude clinic in Huntsville will be overseen by both Clinical Operations and the Affiliate Office in Memphis to provide more of the look and feel of a St. Jude clinic. The goal, as always, is to provide more St. Jude care close to home, and this new approach offers the flexibility and resources to meet the St. Jude mission. A few years in the making, we are excited to begin this new journey.

St. Jude Affiliate Sites

Baton Rouge, LA

Our Lady of the Lake Children’s Hospital – Our Lady of the Lake Regional Medical Center

Jeffrey Deyo, MD, PhD Medical Director

Kacie Sims, MD

Sakshi Bami, MD

Alexandria Broadnax, MD

Katherine Helo, NP

Jessica Templet, PA-C

Joseph Kent, PA

Charlotte, NC

Novant Health Hemby Children’s Hospital

Christine Bolen, MD Medical Director

Jessica Bell, MD

Jenny McDaniel, MD

Joanne McManaman, MD

Felipe Bautista, MD

Holly Edington, MD

Courtney Saine, NP

Jennifer Weisner, NP

Andria Kokoszka, NP

Courtney Carr, NP

Huntsville, AL

Huntsville Hospital for Women & Children – Huntsville Hospital

Marla Daves, MD Medical Director

Sana Mohiuddin, MD

Jamie Musick, MD

Heidi Simpson, NP

Megan Vann, NP

Emily Clawson, NP

Ameila Jantz, NP

Johnson City, TN

Niswonger Children’s Hospital – Ballad Health

East Tennessee State University

Marcela Popescu, MD

Medical Director

Myesa Emberesh, MD

Meghan Srinivas, MD

Angela Willocks, RN, MSN, CFNP

Lauren Wyatt, NP

Amy Shaw, NP

Peoria, IL

OSF HealthCare Children’s Hospital of Illinois

University of Illinois College of Medicine at Peoria

Brinda Mehta, MD

Medical Director

Prerna Kumar, MD

Mary Beth Ross, MD, PhD

Jennifer Light, MD

Maggie Nagel, MD

Kay Saving, MD

Beth Speckhart, NP

Sue Gaitros, NP

Diana Simmons, NP

Dana Stephens, NP

Shreveport, LA

Ochsner LSU Health – Shreveport

Ayo Olanrewaju, MD

Medical Director

Elizabeth Wadhwa, MD

Alejandra Rosales, MD

Diana Townsend, NP

Amanda Saunders, NP

Springfield, MO

Mercy Children’s Hospital – Springfield

Mercy Health System

Francisca Fasipe, MD

Medical Director

Batool El-Atoum, MD

Carolyn Sullivan, NP

Danielle Lee, NP

Administration

Carolyn Russo, MD Medical Director

Jennifer Morgan, MSN Nursing Director

Nica Graunke, MPH Clinical Operations Director

Linda Stout, MD Rotating Physician

Patti Pease, NP, APN, RN Advanced Practice Provider Lead

Tulsa, OK

The Children’s Hospital at Saint Francis

Ashraf Mohamed, MD Medical Director

Martina Hum, MD

Shilpa Shukla, MD

Jill Salo, MD

Sara Mednansky, MD

Cori Ryan, NP

Allison Taylor, NP

St. Jude Global

Cancer

develops in about 400,000 children worldwide annually, and 90% of those children live in resource-limited countries. Fewer than 30% have successful outcomes.

When St. Jude launched the St. Jude Global initiative in 2018, it was an effort to build on the institution’s decades of mentorship and collaboration with hospitals around the world, with the vision that every child who receives a diagnosis of cancer or another catastrophic disease has access to quality care and treatment.

In 2024, St. Jude Global continued solidifying its work with medical institutions and foundations around the world through seven regional and 15 transversal programs and a growing number of projects, research initiatives, and educational opportunities.

Among these efforts is the St. Jude Global Alliance, which connects and empowers institutions and foundations worldwide. Launched in December 2018, the Alliance is a global community working to advance care for children with cancer or other catastrophic diseases. It takes a multilevel approach to developing global, national, regional, and hospital-based initiatives centered on its member institutions. In 2024, the Alliance grew to 324 members, including medical institutions and foundations from more than 80 countries.

At the sixth annual Global Alliance Convening, which took place December 10–12, 2024, in Memphis, more than 240 Alliance members from 185 organizations representing 68 countries came together. More than 800 members attended hybrid plenary sessions. The St. Jude Global team co-designed the program with Alliance members to include 11 general sessions, 54 interactive breakout sessions, and 116 posters and exhibition items. The theme, “Global Voices Exchanging Knowledge,” encouraged and empowered attendees to connect through knowledge sharing, amplifying successes, and inspiring action to transform care for children everywhere.

EDUCATION AND DEVELOPMENT

In 2003, St. Jude began working with partner institutions around the globe to create fellowship training programs at those institutions to build capacity and improve access to care for children with cancer. This effort has grown to include the development of fellowship training programs across eight institutions in seven countries. To strategically fill the specialist gaps across regions, trainees are selected according to country- or facilitylevel needs, with a plan for employment to begin immediately after completing training. These fellowships are modeled after those at St. Jude and consist of two- or three-year training programs that physicians enter after completing a pediatric residency. Beginning with the academic year in July 2024, the St. Jude Global Academy became an official ACGME-I (Accreditation Council for Graduate Medical Education–International)–sponsoring institution. To date, 130 specialists have graduated from St. Jude Global collaborating programs.

The St. Jude Global Academy seminars are skill-setting, certificate-based short training programs that enroll about 300 individuals per year. These seminars provide structured learning experiences in key areas that are relevant globally and are offered either as hands-on experiences at St. Jude or through blended formats that are both online and in person. In 2024, St. Jude Global Academies focused on neuro-oncology, critical care, and palliative care. Across these seminars and other educational opportunities, the online platform Cure4Kids provides critical resources. In September 2024, the platform relaunched to provide even more educational resources in a streamlined and easy-to-use new design.

The Department of Global Pediatric Medicine, in collaboration with the St. Jude Children’s Research Hospital Graduate School of Biomedical Sciences, developed the Master of Science in Global Child Health degree program in 2019. The sixth class of 10 students began its two-year program of study in 2024.

Following graduation, the Global Scholars conduct projects that the Global Pediatric Medicine department funds for two years. More than 10 of these projects were launched in 2024, and 12 were approved.

RESEARCH AND IMPLEMENTATION

St. Jude Global and the St. Jude Comprehensive Cancer Center continued their partnership on a phase 2 clinical trial titled “Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age with NTRK1/2/3 or ROS1-fused CNS Tumors” (GLOBOTRK) (NCT06528691).

The study was activated in 2024 and includes seven Alliance partner hospitals in five countries (Brazil, Egypt, India, Jordan, and Peru). An external clinical research organization was selected in 2024 to manage the study, and the St. Jude Institutional Review Board and the Clinical Trials Scientific Review Committee have approved the protocol, which is now active for accrual.

The SJCARES implementation platform continued to grow its suite of tools in 2024, including the Adapted Resource and Implementation Application (ARIA) Guide, which enables St. Jude Global to provide essential guidance to the clinicians who need it most. These childhood cancer management guidelines are made possible through the partnership between St. Jude Global and the International Society of Paediatric Oncology, along with ongoing global support from the Paediatric Radiation Oncology Society, the International Society of Paediatric Surgical Oncology, and Childhood Cancer International. The ARIA Guide can be applied across a range of geographic and resource-diverse settings and is freely available to health care providers worldwide through the ARIA Guide web portal. So far, 22 guidelines are available, and more than 50 are in progress.

The SJCARES Registry, PrOFILE, Global Packages, and Systems & Policies tools continued to expand during 2024. As part of these comprehensive efforts, the National Cancer Control Planning integrating Children, Adolescents, and

Young Adults, a policy science–driven workshop series delivered in four languages to help health ministries develop national cancer control plans that include childhood cancer, enrolled its third cohort of ministry-led teams, helping reach 39 countries.

The St. Jude Global Diagnostic Innovations Using Value-based Implementation Models to Increase Access (DIVIA) Project made great progress in 2024. In partnership with the Department of Pathology and the Center for Applied Bioinformatics, the project has established and executed feasibility-assessment endeavors at two Alliance sites: Tata Memorial Center in Kolkata, India, and Hospital do Amor Barretos in Barretos, Brazil. Each site has cleared regulatory, legal, and financial hurdles, and sequencing quality control work has been successfully completed toward generating the quality FASTQ files (i.e., text-based files that store raw DNA and RNA sequencing data and quality scores) needed for the successful classification of pediatric cancers.

GLOBAL PARTNERSHIPS

Addressing disparities in access to and quality of care for children with catastrophic diseases requires a systemic approach that addresses the multilayered dimension, from micro to macro, with a focus on the empowerment of partners. In 2018 and again in 2022, the World Health Organization (WHO) designated St. Jude as the first and only WHO Collaborating Centre for Childhood Cancer. St. Jude supports this work across three areas: 1) Support the WHO in including childhood cancer in national cancer control plans through tools for prioritization, costing, and framework for monitoring and evaluation. 2) Support the

WHO in developing tools and platforms for innovation, including diffusion in childhood cancer management, research, and education. 3) Support the WHO in strengthening childhood cancer control through technical support, training materials, and stakeholder engagement.

In 2018, St. Jude worked with the WHO and global partners to launch the Global Initiative for Childhood Cancer (GICC), with the goal of reaching at least 60% survival for children with cancer and saving 1 million more children by 2030 while reducing suffering. St. Jude serves as a technical and implementation partner, providing subject matter expertise, supporting technical tools and packages, and facilitating workshops and projects with national and global stakeholders. Through 2024, 76 countries were engaged in GICC, including 44 that have a signed Memorandum from their Ministry of Health as a focus country.

In 2021, St. Jude and the WHO announced the creation of the Global Platform for Access to Childhood Cancer Medicines to provide an uninterrupted supply of quality-assured cancer medicines to lowresource countries. Co-designing with the first six pilot countries (Ecuador, Jordan, Mongolia, Nepal, Uzbekistan, and Zambia) took place throughout 2024, with a target of the first medicines to arrive in early 2025. This work included collaborative readiness assessments of supply chain and clinical capacity, as well as country governance to foster ownership opportunities. The Global Platform saw the largest joint tender in global oncology medicines conducted by UNICEF and the PAHO Strategic Fund. It included 69 essential medicines and formulations after two rounds of requests for proposals.

St. Jude Graduate School

The St. Jude Children’s Research Hospital Graduate School of Biomedical Sciences comprises three current degree-granting programs:

Doctorate of Philosophy in Biomedical Sciences (PhD-BMS) training young scientists to advance our understanding of the molecular basis of disease and therapy

Master of Science in Global Child Health (MS-GCH) developing a global community of agents of change and leaders dedicated to improving children’s health worldwide

Master of Science in Clinical Investigations (MS-Cl) training clinicians and medical professionals to perform clinical research and conduct clinical trials

In the fall of 2025, the Graduate School will launch its newest graduate program, a Master of Science in Applied Biomedical Data Sciences, which will train students to be effective and collaborative biomedical data scientists. Approximately 220 faculty members and staff at St. Jude are now formal Graduate School faculty members involved in teaching, mentoring, serving on committees, and continuing to enhance the school’s future. In 2024, 78 PhD-BMS students, 21 MS-GCH students, and 17 MS-Cl students were actively enrolled.

Drawing on the deep expertise of a leading biomedical research faculty focused on the eradication of catastrophic childhood diseases and state-of-the-art infrastructure and technological support available at St. Jude, the PhD-BMS Program has now graduated 24 doctoral awardees, who have begun to contribute to diverse fields, including professional and industry research, scientific policy, academic postdoctoral studies, scientific writing and communications, and faculty at St. Jude. The program is led by Associate Dean Wilson Clements, PhD, associate member in the Department of Hematology; Assistant Dean Cassandra VanDunk, PhD; and Program Specialist Alex Frawley, MS. In the fall of 2024, the PhD-BMS Program welcomed 16 new matriculants.

Led by Associate Dean Shaloo Puri, MBBS, DTCD, MPH, MPA; Assistant Dean Julie Laveglia, EDD;

and Program Specialist Whitney Horton, MPS, who joined the staff in 2024, the MS-GCH Program has a mission to provide transformative education, facilitate collaborative opportunities, build capacities, and cultivate a diverse community of agents of change with the overall aim of enhancing equity, access, and quality of health care for children globally. The program completed its fifth academic year in 2024 and admitted another cohort of 11 health care professionals. The Winter Intersession welcomed back 20 students who attended leadership, management, and communication workshops on campus. In May, the fourth cohort participated in the Commencement ceremony to receive their diplomas. During the summer, multiple cohorts (students and alumni) came to Memphis for two weeks to participate in Orientation, Summer Intersession, Professional Development, Convocation, and Commencement. The MS-GCH Program has 38 alumni living in more than 20 countries.

Co-led by Associate Deans Patricia Flynn, MD; and Victor Santana, MD; Assistant Dean Sally Utech, PhD; and Program Specialist Jimmi Lampley, MS, the MS-CI Program provides students with a transformative education that will generate a cadre of health care professionals who are adept at designing, conducting, and reporting clinical investigations that promote human health. The program creates a unique opportunity to understand these concepts in a pediatric and young adult research setting, leveraging the expertise of St. Jude faculty and staff in undertaking clinical research. The MS-CI Program graduated its second class of five students in 2024, all remaining active in clinical research and patient care. In the fall of 2024,

the program matriculated its third class of ten students, composed of postdoctoral fellows, St. Jude faculty, and research and medical staff members.

Renovation of the Graduate School space in the Marlo Thomas Center was completed in the spring of 2024, adding additional administrative offices and cubicles needed to accommodate the Graduate School’s growing staff. The Graduate School has leased new space for student study carrels in the Inspiration4 Advanced Research Center, doubling the previous study capacity. New student activity center space is also being leased on the plaza level of the Danny Thomas Research Tower.

Under the leadership of Steven Varga, PhD, Dean of the Graduate School of Biomedical Sciences, the school submitted its initial application for membership to the Southern Association of Colleges and Schools Commission on Colleges in February of 2024. This crucial step begins the accreditation process, which ensures a school maintains the highest educational standards, as judged by external evaluators.

Finally, none of these activities and accomplishments would have been possible without the support of our Board of Trustees. The Graduate School relies heavily on the advice and insight this group of dedicated volunteers provides.

Graduate School Board of Trustees

Steven Bares, PhD, MBA (Chair) Former President and Executive Director Memphis Bioworks Foundation

William Troutt, PhD (Vice Chair) President Emeritus Rhodes College

James R. Downing, MD President & CEO

St. Jude Children’s Research Hospital

Gabriel Haddad, MD Chairman, Department of Pediatrics University of California San Diego

Sarah Larsen, PhD Vice Provost and Dean of the Graduate School Interim Dean, Graduate College of Social Work Professor of Chemistry University of Houston

Ryan Potts, PhD Vice President Head of the Induced Proximity Platform Amgen, Inc.

Carolyn Smith, PhD Dean, Graduate School of Biomedical Sciences Vice President, Education Affairs

William R. Brinkley BRASS Chair Baylor College of Medicine

J. Paul Taylor, MD, PhD Executive Vice President and Scientific Director

St. Jude Children’s Research Hospital

FACULTY, FELLOWS & STUDENTS

Biostatistics

CHAIR

Motomi Mori, PhD, MBA1; Endowed Chair in Biostatistics

Design and analysis of early phase clinical trials, biomarker discovery and validation, risk prediction models

MEMBERS

Cheng Cheng, PhD1

Statistical methods in cancer biology, clinical & translational studies

Meenakshi Devidas, PhD, MBA1,2

Biostatistics, pediatric hematology and oncology

Guolian Kang, PhD1

Statistical genetics/genomics, modeling of complex data

Yimei Li, PhD1

Statistical analysis of complex imaging data, survival data analysis & clinical trial design

Arzu Onar-Thomas, PhD1

Phase 1/2 designs, survival analysis, Bayesian statistics

Stanley Pounds, PhD1

Statistical cancer multi-omics; statistical pharmacogenomics

Deokumar Srivastava, PhD1

Clinical trials, robust methods, survival analysis

Li Tang, PhD1

Prediction, validation, diagnostic testing, microbiome analysis

ASSOCIATE MEMBERS

Sedigheh Mirzaei, PhD1

Statistical methods for incomplete survival data, cancer survivorship

Haitao Pan, PhD1

Bayesian dose-finding clinical trials design, adaptive design for single-arm and randomized clinical trials, pediatric extrapolation

ASSISTANT MEMBERS

Cai Li, PhD1

Statistical learning and computing methods for neurodegeneration

Qian Li, PhD1

High-dimensional multiomics, longitudinal modeling, statistical learning

Qijun Li, PhD1

Novel statistical methods to address statistical issues that widely arise in observational studies

Subodh Selukar, PhD1

Design and sequential monitoring of clinical trials

Yiwang Zhou, PhD1

Statistical methods for precision-medicine studies

INSTRUCTOR

Zachary Wooten, PhD

Enhancing contouring quality assurance in radiation oncology by using AI and machine learning

Bone Marrow Transplantation & Cellular Therapy

CHAIR

Stephen Gottschalk, MD1; Endowed Chair in Bone Marrow Transplantation & Cellular Therapy Cancer immunotherapy, cellular therapy, hematopoietic cell transplantation

MEMBER

Brandon Triplett, MD1; Deputy Clinical Director Hematopoietic cell transplantation

ASSOCIATE MEMBERS

Giedre Krenciute, PhD1 Cellular therapy for brain tumors

Ewelina Mamcarz, MD3

Swati Naik, MBBS

Cellular therapy for hematologic malignancies, hematopoietic cell transplantation

Amr Qudeimat, MD Hematopoietic cell transplantation

Akshay Sharma, MBBS1

Gene therapy and transplantation for nonmalignant hematologic diseases

Ashok Srinivasan, MD3

Paulina Velasquez, MD1 Cellular therapy for hematologic malignancies

ASSISTANT MEMBERS

Senthil Bhoopalan, MBBS, PhD1 Gene therapy & genome editing

Christopher DeRenzo, MD, MBA1

Cellular therapy for solid tumors

Rebecca Epperly, MD

Cellular therapy for pediatric malignancies

Ali Suliman, MD, MSc Hematopoietic cell transplantation

Aimee Talleur, MD1

Cellular therapy for hematologic malignancies

Caitlin Zebley, MD, PhD

Cellular therapy and T-cell differentiation

Cell & Molecular Biology

CHAIR

J. Paul Taylor, MD, PhD1; Executive

Vice President, Scientific Director, Edward F. Barry Endowed Chair in Cell & Molecular Biology

Molecular genetics of neurological diseases

VICE-CHAIR

Peter McKinnon, PhD1; Endowed Chair in Pediatric Neurological Diseases

DNA-damage responses in the nervous system

MEMBERS

Mondira Kundu, MD, PhD1

Autophagy-related proteins in health & human disease

Heather Mefford, MD, PhD1

Genetics of pediatric neurological disease

Stacey Ogden, PhD1

Mechanisms of Hedgehog signal transduction

ASSOCIATE MEMBERS

Joseph Opferman, PhD1

Regulation of cell death & mitochondrial function

Jasmine Plummer, PhD1,2

Multi-omics examination of genetic risk as a factor of oncogenesis

Shondra Pruett-Miller, PhD1

Genome-editing technologies

ASSISTANT MEMBERS

Fernando Cruz Alsina, PhD1

Molecular and cellular mechanisms that drive neural differentiation and maturation during brain development

Chi-Lun Chang, PhD1

Dynamic regulation of interorganelle communication

Bryan Gibson, PhD1

Impact of phase transitions on higher-order genome structure and human disease

Dolores Irala, PhD1

Role of astrocyte dysfunction in neurodevelopmental disorders

Andrew Kodani, PhD3

Chemical Biology & Therapeutics

CHAIR

Aseem Ansari, PhD1; Robert J. Ulrich Endowed Chair in Chemical Biology & Therapeutics

Synthetic gene regulators for personalized medicine, artificial transcription factors to control stem cell fate choices

MEMBERS

Taosheng Chen, PhD, PMP1

Xenobiotic receptors and therapeutic responses

Richard Lee, PhD1; Endowed Chair in Medicinal Chemistry

Discovery of new antibiotic agents and structure-based drug design

ASSOCIATE MEMBERS

Marcus Fischer, PhD1

Protein conformational landscapes for ligand discovery

Anang Shelat, PhD1

Translational research & chemical biology

ASSISTANT MEMBERS

Daniel Blair, PhD1

Covalent inhibitors and automated synthesis

Tommaso Cupido, PhD1

Protein machines & chemical probe discovery

Hai Dao, PhD1

Development of novel chemical biology tools to study abnormal chromatin processes

INSTRUCTOR

Supriya Sarvode, MD

Therapeutic development

Computational Biology

INTERIM CHAIR

Jiyang Yu, PhD1

Systems biology, systems immunology, & translational oncology

MEMBERS

Zhaoming Wang, PhD1,2

Genetic epidemiology of pediatric cancer & survivorship

Jinghui Zhang, PhD1; Endowed Chair in Bioinformatics

Cancer genomic variant analysis & visualization

ASSOCIATE MEMBERS

Xiang Chen, PhD1

OMICS integration & tumor heterogeneity by machine

Yong Cheng, PhD1,2 Cis-regulatory modules in hematopoiesis & its disorders

Paul Geeleher, PhD1

Computational methods and drug repositioning

Xiaotu Ma, PhD1

Mathematical modeling of cancer-initiating events

ASSISTANT MEMBERS

Brian Abraham, PhD1

Transcriptional control of cell identity and disease learning approaches

Samuel Brady, PhD1,2

Cancer genomics and pharmacology in pediatric cancer treatment

Xin Zhou, PhD1

Data visualization and real-time analysis

Developmental Neurobiology

CHAIR

Michael Dyer, PhD1; Richard C. Shadyac Endowed Chair in Pediatric Cancer Research

Retinal development, retinoblastoma, & pediatric solid tumor translational research

MEMBERS

Suzanne Baker, PhD1; Endowed Chair in Brain Tumor Research

Genetic and epigenetic drivers of pediatric high-grade glioma

James Morgan, PhD; Edna and Albert Abdo Shahdam Endowed Chair in Basic Research Control of neuronal death & differentiation

Paul Northcott, PhD1; Endowed Chair in Molecular Neuro-Oncology Genomics & developmental biology of childhood brain tumors

Junmin Peng, PhD1,2 Proteomics & metabolomics in human disease

David Solecki, PhD1

Cell polarity in neuron precursor differentiation

J. Paul Taylor, MD, PhD1,2; Executive Vice President, Scientific Director, Edward F. Barry Endowed Chair in Cell & Molecular Biology

Molecular genetics of neurological diseases

Stanislav S. Zakharenko, MD, PhD1

Neural circuits of learning, memory, and their dysfunction in neurodevelopmental psychiatric disorders

ASSOCIATE MEMBERS Xinwei Cao, PhD1

Growth control during neural tube development

Fabio Demontis, PhD1

Protein homeostasis & stress sensing in skeletal muscle aging

Young-Goo Han, PhD1

Regulatory mechanisms of neural progenitors in brain development, diseases, & evolution

Khaled Khairy, PhD

Biomechanics-based computational models as priors for biological-image analysis

Stephen Mack, PhD1

Pediatric brain tumors, cancer epigenetics, therapeutics, models

Jamy Peng, PhD1

Epigenetic regulation of stem cell functions

Jasmine Plummer, PhD1

Multi-omics examination of genetic risk as a factor of oncogenesis

Elizabeth Stewart, MD1,2

Translational research of pediatric solid tumors

ASSISTANT MEMBERS

Jay Bikoff, PhD1

Neural circuits controlling movement

Yuuta Imoto, PhD1

Membrane trafficking during synaptic vesicle recycling

Lindsay Schwarz, PhD1

Mechanisms of neuromodulatory circuit organization

Jason Vevea, PhD1

Mechanisms of organelle quality control and organelle trafficking in neurons

Diagnostic Imaging

(Radiology as of Q3 2024)

CHAIR

Andrew Smith, MD, PhD; Endowed Chair in Diagnostic Imaging

Clinical applications of artificial intelligence in radiology

MEMBERS

Sue Kaste, DO4

Robert Kaufman, MD4

Mary (Beth) McCarville, MD4

Wilburn Reddick, PhD1

CNS structural changes during and after therapy

Barry Shulkin, MD, MBA

PET imaging evaluation of pediatric tumors

Ranganatha Sitaram, PhD

Multimodal functional brain imaging & neurorehabilitation

Michael Temple, MD

Advancing pediatric interventional oncology techniques in children

ASSOCIATE MEMBERS

Allison Aguado, MD

Evaluating the safety and effectiveness of interventional radiology therapies for children with cancer

Asim Bag, MBBS, MD1

Response to immunotherapy & radiation therapy, cancer therapy–induced neuroinflammation & brain damage, imaging low-grade gliomas

Hedieh Khalatbari, MD3

Soft-tissue sarcomas and bone tumors

Noah Sabin, MD, JD

Imaging of brain tumors & side effects of therapy

Paul Yi, MD1

Human–computer interaction to augment collaboration between AI & humans in medicine

ASSISTANT MEMBERS

Zachary Abramson, MD, DMD

Quantitative imaging, computeraided three-dimensional modeling

Puneet Bagga, PhD

Metabolic imaging, MR spectroscopy, molecular MRI, & cancer metabolism

Kiel Neumann, PhD1

Translational Imaging and radiopharmaceutical development

Devendra Sawant, MD, PhD

Molecular imaging, radionucleotide therapy, and cancer biology

INSTRUCTORS

Stuart McAfee, PhD

Network interactions between cerebellum, brainstem, and cerebral cortex in normal development and disease

Soniya Pinto, MD

Imaging of neurologic complications of CAR T–cells therapy

Epidemiology & Cancer Control

CHAIR

Gregory Armstrong, MD, MSCE1; Endowed Chair in Epidemiology & Cancer Control Cancer survivorship & long-term follow-up

MEMBERS

Heather Brandt, PhD1

HPV vaccination and cervical cancer screening

Tara Brinkman, PhD1,2 Psychosocial outcomes of pediatric cancer

Joshua Burns, PhD1; Jeweler’s Charity Fund Endowed Chair in Cancer Survivorship Gait and movement disorders of childhood

I-Chan Huang, PhD

Patient-reported outcomes measurement after pediatric cancer

Melissa Hudson, MD1,2; The Charles E. Williams Endowed Chair of Oncology – Cancer Survivorship Health outcomes after childhood cancer

Kirsten Ness, PT, PhD, FAPTA1; Endowed Chair in Cancer Survivorship

Physical health and accelerated aging in childhood cancer survivors

Leslie Robison, PhD4

Zhaoming Wang, PhD1

Genetic epidemiology of pediatric cancer & survivorship

Yutaka Yasui, PhD1

Genetics & risk of therapyrelated outcomes

ASSOCIATE MEMBERS

Nickhill Bhakta, MD, MPH1,2

Global health, survivorship, epidemiology, childhood leukemias

Angela Delaney Freedman, MD2

Hypothalamic/pituitary dysfunction in childhood cancer survivors

Daniel Mulrooney, MD, MS1,2

Cardiovascular outcomes of cancer therapy

ASSISTANT MEMBERS

Yadav Sapkota, PhD1

Genomic basis of pediatric cancer outcomes

Carmen Wilson, PhD1

Late effects of childhood cancer therapy

Genetics

MEMBERS

Alessandra d’Azzo, PhD1; Jewelers

Charity Fund Endowed Chair in Genetics and Gene Therapy Lysosomal/proteasomal function in health & disease

Gerard Grosveld, PhD4

Global Pediatric Medicine

CHAIR

Carlos Rodriguez-Galindo, MD1; Executive Vice President, Four Stars of Chicago Chair in International Pediatric Outreach Global medicine, pediatric solid tumors

MEMBERS

Miguela Caniza, MD, MPH1 Global health, infection care and control

Meenakshi Devidas, PhD, MBA1 Biostatistics, pediatric hematology and oncology

Jane Hankins, MD, MS1 Sickle cell disease, transition to adult care & health outcomes during adolescence & young adulthood

Sima Jeha, MD1

Global health, childhood leukemias, developmental therapeutics

Gaston Rivera, MD4

Victor Santana, MD1; Charles Pratt Chair in Solid Tumor Research Global health, novel therapeutics, neuroblastoma, research ethics

ASSOCIATE MEMBERS

Asya Agulnik, MD, MPH1

Global health, pediatric oncocritical care, quality improvement

Nickhill Bhakta, MD, MPH1 Global health, survivorship, epidemiology, childhood leukemias

Paola Friedrich, MD, MPH1 Global health, health disparities, health services, pediatric solid tumors

Catherine Lam, MD, MPH1 Global health, health systems, pediatric solid tumors

Ibrahim Qaddoumi, MD, MS1

Global health, brain tumors, telemedicine, retinoblastoma

Teresa Santiago, MD2 Laboratory quality improvement & assessment

Jeremy Slone, MD, MPH1 Global pediatric cancer epidemiology

ASSISTANT MEMBERS

Anita Arias Prado, MD2

Capacity building in pediatric critical care

Dylan Graetz, MD1

Global health, patientcentered care, solid tumors

Saman Hashmi, MD

Capacity building in global pediatric oncology

Michael McNeil, MD, MPH1

Defining the state of palliative care for children with cancer in resource-constrained settings

Daniel Moreira Ridsdale, MD1 Global pediatric oncology, evidence-based education, pediatric CNS tumors

Sheena Mukkada, MD, MPH1 Global health, infection care & control

INSTRUCTORS

Caitlyn Duffy, MD

Application of implementation science to address the global pediatric cancer survival gap

Marta Salek, MD, MPH

Optimizing care and quality of life for children with cancer on a global scale

Hematology

CHAIR

Mitchell Weiss, MD, PhD1; Arthur Nienhuis Endowed Chair in Hematology

Blood development, red blood cell biology, novel therapeuticapproaches to sickle cell disease and β-thalassemia

MEMBERS

John Crispino, PhD, MBA1; Wall Street Committee Endowed Chair

Mechanisms of leukemogenesis, benign & malignant blood disorders

Shannon McKinney-Freeman, PhD1

Mechanisms of hematopoietic stem cell development & transplantation

Ellis Neufeld, MD, PhD; Executive Vice President, Clinical Director, John and Lorine Thrasher Endowed Chair in Pediatric Medicine Patient-oriented studies in nonmalignant hematology

Clifford Takemoto, MD1; Lemuel Diggs Endowed Chair in Sickle Cell Disease Hemostasis & thrombosis, vascular malformations, bone marrow failure

Winfred Wang, MD4

ASSOCIATE MEMBERS

Yong Cheng, PhD1

Cis-regulatory modules in hematopoiesis & its disorders

Wilson Clements, PhD1

Hematopoietic development & leukemia

Ulrike Reiss, MD1

Bleeding disorders, gene therapy for hemophilia, bone marrow failure

Carolyn Russo, MD

Quality improvement inclinical networks

Shengdar Tsai, PhD1

Genome-engineering technologies for therapeutics

Jonathan Yen, PhD1

Translation of therapeutic genome engineering technologies to treat hemoglobinopathies

ASSISTANT MEMBERS

Nidhi Bhatt, MD

Health communication & implementation science

Marta Derecka, PhD1

Hematopoiesis & the bone marrow microenvironment

Rohith Jesudas, MBBS Hemostasis, thrombosis, & immune cytopenias

Alyssa Kennedy, MD, PhD Molecular drivers behind bone marrow failure and leukemiapredisposition syndromes

Alexis Leonard, MD Curative strategies for sickle cell disease

Dirk Loeffler, PhD1 Cancer stem cells & clonal hematopoiesis

Yogindra Persaud, MD Advancing the knowledge of sickle cell disease

Parul Rai, MD Cardiac injury in sickle cell disease

Marcin Wlodarski, MD, PhD1 Inherited bone marrow failure & MDS-predisposition syndromes

Masayuki Yamashita, MD, PhD1 Cell death programs that control hematopoietic stem cell survival vs. elimination

INSTRUCTORS

Georgios Christakopoulos, MD Development of genome-editing strategies to cure β-thalassemia

Richa Sharma, MD3

RESEARCH ASSOCIATE Phillip Doerfler, PhD3

ADJUNCT MEMBERS

Kenneth Ataga, MD Sickle cell disease and related hemoglobinopathies, thalassemia and other red blood cell disorders

Francisca Fasipe, MD Leukemia, lymphoma, hemoglobinopathies, and solid tumors

Marcela Popescu, MD Clinical pediatric hematology

Host–Microbe Interactions

CHAIR

Victor Torres, PhD1; Albert and Rosemary Joseph Endowed Chair in Host-Microbe Interactions Interactions between antimicrobial-resistant bacteria and their mammalian host

MEMBERS

Jason Rosch, PhD1

Bacterial genomics & pathogenesis

Stacey Schultz-Cherry, PhD1 Pathogenesis of influenza & enteric virus infections

Paul Thomas, PhD1 Mechanisms of antiviral and antitumor immunity

Elaine Tuomanen, MD1 Pathogenesis of pneumococcal infection

Richard Webby, PhD1 Influenza virus pathogenicity

ASSOCIATE MEMBER

Charles Russell, PhD1

Respiratory viruses: disease, cures, and prevention

ASSISTANT MEMBER

Jeremy Crawford, PhD1

Translational immunology, immunotherapy, and immunoinformatics

INSTRUCTOR

Bradley Muller, MD2

Gamma-delta T-cell receptor biology in gamma-delta T-cell acute lymphoblastic leukemia

Immunology

INTERIM CHAIR

Terrence L. Geiger, MD, PhD1,2; Endowed Chair in Pediatrics

T-cell regulation, adoptive immunotherapy

VICE-CHAIR

Thirumala-Devi Kanneganti, PhD1; Rose Marie Thomas Endowed Chair in Immunology

Mechanisms of host defense & inflammation

MEMBERS

Hongbo Chi, PhD1; Robert G. Webster Endowed Chair in Immunology

Immune signaling and metabolism

Peter Doherty, PhD4; Nobel Laureate

Douglas Green, PhD1; Peter Doherty

Endowed Chair in Immunology

Cell death, autophagy, and immune function

Benjamin Youngblood, PhD1

T-cell memory differentiation, exhaustion, and immunotherapy

ASSOCIATE MEMBERS

Yongqiang Feng, PhD1

Epigenetic & transcriptional basis of T-cell immunity

Bo Hu, PhD1

Neuroimmunology and interrogations of neuroimmune interactions in health and disease

ASSISTANT MEMBER

Yunlong Zhao, PhD1

Molecular and cellular cues that influence antitumor responses utilizing membrane-reconstitution systems and advanced imaging

Infectious Diseases

CHAIR

Octavio Ramilo, MD1; Endowed Chair in Infectious Diseases Viral respiratory infections and early life immunity

MEMBERS

Miguela Caniza, MD, MPH1,2 Global health, infection care and control

Patricia Flynn, MD1; Arthur Ashe Endowed Chair in Pediatric AIDS Research HIV/AIDS in children & infections in children with cancer

Aditya Gaur, MD, MBBS1 Clinical research in HIV prevention & treatment

Hana Hakim, MD Infection prevention and control

Julia Hurwitz, PhD1 Pathogen/vaccine-induced immunity, nuclear hormones

Gabriela Marón Alfaro, MD1 Infectious complications in transplant patients

Asuncion Mejias, MD, PhD, MsCS Viral respiratory infections and perinatal infections

Steven Varga, PhD1; Endowed Chair–Dean Graduate School of Biomedical Sciences Immunopathogenesis of respiratory viruses

Robert Webster, PhD4

Joshua Wolf, PhD, MBBS1 Prediction, prevention, & treatment of infections in immunocompromised children

ASSOCIATE MEMBERS

Elisabeth Adderson, MD1 Epidemiology & treatment of infections

Diego Hijano, MD, MSc1

Host–pathogen interactions of respiratory virus

Katherine Knapp, MD

Perinatal HIV exposure/ HIV clinical trials

Nehali Patel, MD1 HIV clinical care

Megan Wilkins, PhD2

Clinical & research psychological services for youth with HIV/AIDS

ASSISTANT MEMBERS

Lisa Hiskey, DO

Optimizing antimicrobial use in immunocompromised pediatric patients through infectious diseases diagnostics

Ellie Margolis, MD, PhD1 Microbiome dynamics in immunocompromised patients

Sheena Mukkada, MD, MPH1,2 Global health, infection care and control

INSTRUCTOR

Amanda Green, MD

Human immune responses to co-infection and chronic viruses, including HIV and CMV

ADJUNCT MEMBERS

Nicholas Hysmith, MD, MS, FAAP Emerging infections & hospital epidemiology

Jonathan A. McCullers, MD

Interactions between viruses & bacteria

Oncology

CHAIR

Julie Park, MD; Endowed Chair in Pediatric Oncology

Translational research to improve survival of children with cancer

MEMBERS

Gregory Armstrong, MD, MSCE1,2; Endowed Chair in Epidemiology & Cancer Control

Pediatric neuro-oncology & cancer survivorship

Sara Federico, MD1

Drug development, pediatric soft-tissue sarcomas

Elizabeth Fox, MD1

Developmental therapeutics in pediatric oncology

Wayne Furman, MD4

Amar Gajjar, MD2; Scott and Tracie Hamilton Endowed Chair in the Brain Tumor Program Novel treatments for children with brain tumors

Daniel Green, MD1

Adverse hepatic, renal, and reproductive effects of therapy

Alejandro Gutierrez, MD1

Molecular basis of chemotherapy resistance to advance novel therapeutics

Melissa Hudson, MD1; The Charles E. Williams Endowed Chair of Oncology – Cancer Survivorship Health outcomes after childhood cancer

Hiroto Inaba, MD, PhD1 New therapeutic strategies for leukemia

Sima Jeha, MD1,2

Global health, childhood leukemias, developmental therapeutics

Sue Kaste, DO2,4

Kim Nichols, MD1

Heritable cancers & primary immunodeficiency syndromes

Alberto Pappo, MD1; Alvin Mauer Endowed Chair New therapies for sarcomas & rare pediatric cancers

Ching-Hon Pui, MD1; Fahad

Nassar Al-Rashid Endowed Chair in Leukemia Research Biology & treatment of childhood leukemia

Raul Ribeiro, MD1

Hematological malignancies

Charles W. M. Roberts, MD, PhD1; Executive Vice President, Lillian R. Cannon Comprehensive Cancer Center Director Endowed Chair SWI/SNF (BAF) chromatin remodeling/tumor suppressor

Giles Robinson, MD1

Origin & genomics of medulloblastoma, translational studies

Jeffrey Rubnitz, MD, PhD3

Jun J. Yang, PhD1,2; Endowed Chair in Pharmacogenomics

Pharmacogenomics of anticancer agents & drug resistance

ASSOCIATE MEMBERS

Nickhill Bhakta, MD, MPH1,2

Global health, survivorship, epidemiology, childhood leukemias

Patrick Campbell, MD, PhD1 Histiocytic disorders, clinical informatics, patient safety

Matthew Ehrhardt, MD, MS1

Late effects of childhood cancer therapy

Paola Friedrich, MD, MPH1,2

Global health, health disparities, health services, pediatric solid tumors

Rebecca Gardner, MD

Development of cellular immunotherapy trials for pediatric cancer

M. Meaghan Granger, MD

Treatment of high-risk neuroblastoma in newly diagnosed and relapsed patients

Mark Hatley, MD, PhD1

Origins of pediatric sarcomas

Sara Helmig, MD1

Sarcoma, thyroid carcinoma, & quality improvement

Liza-Marie Johnson, MD, MPH, MSB1

Ethical issues in pediatrics

Seth Karol, MD1

Toxicity reduction during acute leukemia therapy

Erica Kaye, MD1

Prognostic communication, early integration of palliative care in oncology

Myriam Labelle, PhD1

The role of the microenvironment in cancer metastasis

Catherine Lam, MD, MPH1,2

Global health, health systems, pediatric solid tumors

Deena Levine, MD

Pediatric palliative & end-of-life care

Daniel Mulrooney, MD, MS1

Cardiovascular outcomes of cancer therapy

Ibrahim Qaddoumi, MD, MS1,2

Global health, brain tumors, telemedicine, retinoblastoma

Elizabeth Stewart, MD1

Translational research of pediatric solid tumors

Anna Vinitsky, MD, MS1

Pediatric neuro-oncology & process improvement

ASSISTANT MEMBERS

Aditi Bagchi, MD, PhD

Molecular and genomic characteristics of pediatric brain tumors

Kelsey Bertrand, MSc, MBBS Understanding ependymoma and high-grade glioma

Michael Bishop, MD3

Steven Carey, MD, PhD Management of central nervous system malignancies

Griffin Collins, MD1 Integration of palliative care

Brittany Cowfer, MD1 Prognostic communication in pediatric oncology

Stephanie Dixon, MD1 Pediatric cancer survivorship

Adam Durbin, MD, PhD1 Molecular biology of highrisk pediatric cancers

Aysenur Esen, MD Relapsed or refractory acute myeloid leukemia

Jessica Gartrell, MD

Early phase clinical trial development, sarcomas, liver tumors

Dylan Graetz, MD1,2 Global health, patient-centered care, solid tumors

Lillian Guenther, MD1 Novel genomic targets in osteosarcoma

Saman Hashmi, MD2

Capacity building in global pediatric oncology

Zhongbo Hu, MD, PhD3

Lauren Jerkins, MD

Cellular therapy, quality improvement, and patient safety

Michael McNeil, MD, MPH1,2

Defining the state of palliative care for children with cancer in resource-constrained settings

Daniel Moreira Ridsdale, MD1,2

Global pediatric oncology, evidencebased education, pediatric CNS tumors

Min Ni, PhD1

Genetic and metabolic regulation of childhood development and cancers

Esther Obeng, MD, PhD1

Myeloid malignancies & bone marrow failure syndromes

Anand Patel, MD, PhD1

Tumor recurrence in pediatric rhabdomyosarcoma

Melissa Perrino, MD

Germline predisposition and genetic drivers of cancer

Matthew Rees

Improvement science in the care of children with cancer

Linda Stout, MD

Pediatric oncology

Liqin Zhu, PhD2

Stem cells in normal & malignant development

INSTRUCTORS

Matthew Davis, MD

Acute care of hematology and oncology patients

Caitlyn Duffy, MD2

Application of implementation science to address the global pediatric cancer survival gap

Emily Hanzlik, MD2

Clinical pediatric neuro-oncology & neurologic complications of pediatric cancer

Supriya Sarvode, MD2

Therapeutic development

Dana Tlais, MD

Characterizing the molecular landscape of pediatric high-grade gliomas

Ruth Wang’ondu, MD, PhD

Integration of genetic data from diverse populations to inform treatment of B-cell acute lymphoblastic leukemia

ADJUNCT MEMBERS

Francisca Fasipe, MD

Leukemia, lymphoma, hemoglobinopathies, and solid tumors

Marcela Popescu, MD

Clinical pediatric hematology

Pathology

CHAIR

David Ellison, MBBChir, MA(hons), MSc, MD, PhD; Joan and Roy Gignac Endowed Chair in Pathology & Laboratory Medicine

Pathologic/molecular classification of CNS tumors

MEMBERS

James R. Downing, MD; President and Chief Executive Officer; Donald Pinkel Endowed Chair in Childhood Cancer Treatment

The molecular pathology of acute leukemia

Terrence L. Geiger, MD, PhD1; Endowed Chair in Pediatrics

T-cell regulation, adoptive immunotherapy

Randall Hayden, MD

Clinical microbiology of immunocompromised hosts

Laura Janke, DVM, PhD

Pathology of mouse models of disease

Jeffery Klco, MD, PhD1

Genomic & functional characterization of pediatric myeloid neoplasms

Mondira Kundu, MD, PhD1,2 Autophagy-related proteins in health & human disease

Michael Meagher, PhD4

Charles Mullighan, MBBS(Hons), MSc, MD1; William E. Evans Endowed Chair

Genomic, experimental, & preclinical studies of acute leukemia

Kim Nichols, MD1,2

Heritable cancers & primary immunodeficiency syndromes

Brent Orr, MD, PhD1

Molecular classification of tumors of the nervous system

Jerold Rehg, DVM4

A. Peter Vogel, DVM, PhD1

Pathology of animal models of human disease

Jian Xu, PhD1

Gene regulatory processes controlling stem cell development and blood cancers

Gerard Zambetti, PhD1

The function of p53 in tumor suppression & tumorigenesis

ASSOCIATE MEMBERS

Jason Cheng-Hsuan Chiang, MD, PhD

Diagnosis & classification of CNS tumors

Larissa Furtado, MD Clinical genomics and data management systems

Gabriela Gheorghe, MD

Pediatric leukemias and lymphomas, histiocytic lesions

Yen-Chun Liu, MD, PhD Hematologic malignancies

Harshan Pisharath, DVM, PhD

Animal models of human diseases, preclinical safety

Teresa Santiago, MD

Laboratory quality improvement & assessment

Heather Tillman, DVM, PhD Comparative pathology

Lu Wang, MD, PhD

Genomic profiling & functional analysis of genetic alterations in pediatric tumors

Gang Wu, PhD1

Genome instability, neurodegeneration, brain transcriptomics

Yan Zheng, MD, PhD

Red blood cell genotyping & alloimmunization, cancer immunotherapy

ASSISTANT MEMBERS

Paula Arnold, PhD HLA and hematopoietic cell transplantation

Patrick Blackburn, PhD

Clinical laboratory genetics and genomics

Mohammed Eldomery, MD

Molecular oncology, cancerpredisposition syndromes

Heather Glasgow, PhD

Novel diagnostics for clinical microbiology

Anoop Murthy Kavirayani, DVM, DACVP

Comparative preclinical pathology, experimental/investigative discovery pathology, and toxicologic pathology

Alyssa Kennedy, MD, PhD2

Molecular drivers behind bone marrow failure and leukemiapredisposition syndromes

Mahsa Khanlari, MD

Diagnosis and classification of pediatric hematopoietic neoplasms

Selene Koo, MD, PhD

Molecular classification of pediatric solid tumors

Priya Kumar, MD

Diagnostic capacity building for hematologic malignancies in resource-limited settings

Julieann Lee, MD, MS Clinicopathologic and molecular characterization of pediatric brain tumors

Faizan Malik, MD

Morphologic and molecular characterization of bone and soft-tissue sarcomas and pediatric solid tumors

Denis Noubouossie, MD, PhD

Clinical pathology and transfusion medicine

RESEARCH ASSOCIATE

Lindsey Montefiori, PhD

Lineage-ambiguous leukemia and gene regulatory mechanisms of oncogenic transcription factor activity

Pediatric Medicine

CHAIR

Amar Gajjar, MD; Scott and Tracie Hamilton Endowed Chair in the Brain Tumor Program

Novel treatments for children with brain tumors

MEMBERS

Shannon Dean, MD, MMM; Chief Medical Information Officer Applied clinical informatics

Richard Finkel, MD; George J. Pedersen Endowed Chair in Neurotherapeutics, Director of the Center for Experimental Neurotherapeutics Pediatric neurologic and metabolic diseases

Andrea Gropman, MD; Michael F. Tamer Endowed Chair in Pediatric Neurology

Evaluating neurocognitive injury in inborn errors of metabolism by using multimodal neuroimaging

Raja Khan, MD; Division of Neurology Director

Effect of cancer on central & peripheral nervous systems

Kirsten Ness, PT, PhD, FAPTA1,2 Physical health and accelerated aging in childhood cancer survivors

Ellis Neufeld, MD, PhD2; Executive Vice President, Clinical Director, John & Lorine Thrasher Endowed Chair in Pediatric Medicine Patient-oriented studies in nonmalignant hematology

ASSOCIATE MEMBERS

Angela Delaney Freedman, MD; Division of Endocrinology Director Hypothalamic/pituitary dysfunction in childhood cancer survivors

Asya Agulnik, MD, MPH1,2 Global health, pediatric oncocritical care, quality improvement

Lama Elbahlawan, MD

Pediatric critical care, acute lung injury

Michael Frett, MD; Division of Anesthesiology Director Pediatric anesthesia

Saad Ghafoor, MD

Improvement of pediatric critical care outcomes

Ellen Grishman, MD

Quality of life in pediatric patients with diabetes

Melissa Hines, MD Pediatric critical care, hemophagocytic lymphohistiocytosis

Caitlin Hurley, MD Onco-critical care, HSCT/ immunotherapy patients, long-term care

Belinda Mandrell, PhD, RN, CPNP1; Division of Nursing Research Director Biological mechanism of symptoms associated with cancer & cancer therapy

Jennifer McArthur, DO1 Improving outcomes in critically ill pediatric patients

R. Ray Morrison, MD1; Division of Critical Care Medicine Director Pediatric critical care, myocardial protection

Kavitha Raghavan, MBBS, FRCA Patient safety & quality of care in pediatric anesthesia

Michael Rossi, DO Patient safety & cognitive effects of anesthesia

Luis Trujillo Huaccho, MD Regional anesthesia & anesthetic approach in high-risk cases

Christine Yu, MD Fertility after gonadotoxic therapy

ASSISTANT MEMBERS

Anita Arias Prado, MD Capacity building in pediatric critical care

D. Andrew Elliott, MD; Division of Psychiatry Director Psychiatric effects of cancer and its treatment

TeKesha Henry, DO3

Tzipa Zweig, MD, MS Pediatric pain and palliative care

INSTRUCTORS

Emily Hanzlik, MD Clinical pediatric neuro-oncology & neurologic complications of pediatric cancer

Andrea Heifner, MD Pediatric critical care medicine

ADJUNCT MEMBERS

Mark Corkins, MD Gastroenterology

Patricia Dubin, MD Pulmonology

Terri Finkel, MD, PhD Rheumatology

James Wheless, MD Neurology

Pharmacy & Pharmaceutical Sciences

CHAIR

P. David Rogers, PharmD, PhD1; Endowed Chair in Pharmaceutical Sciences

Molecular and genetic basis of antifungal drug resistance

VICE-CHAIRS

Brooke Bernhardt, PharmD, MS, FCCP

Pharmacogenomics of treatment-related toxicity and outcomes in pediatric cancer

Jun Yang, PhD1; Endowed Chair in Pharmacogenomics

Pharmacogenomics of anticancer agents & drug resistance

MEMBERS

William Evans, PharmD4

James Hoffman, PharmD; Chief Patient Safety Officer Medication safety & outcomes

Markos Leggas, PhD1

Pharmacometabolomic methods to improve therapeutic outcomes and minimize toxicity in the context of pediatric clinical trials

Mary Relling, PharmD4

John Schuetz, PhD1

Regulation & function of ABC transporters

Clinton Stewart, PharmD1

Pharmacology of anticancer drugs in children

ASSOCIATE MEMBERS

Kelly Caudle, PharmD, PhD, BCPS, FCCP

Pharmacogenomics, implementation science, and clinical practice guideline development

Cyrine-Eliana Haidar, PharmD, BCPS, BCOP, FASHP

Clinical pharmacogenomics

Daniel Savic, PhD1

Pharmacogenomics & cis-regulatory architecture of pediatric leukemia

ASSISTANT MEMBERS

Samuel Brady, PhD1

Cancer genomics and pharmacology in pediatric cancer treatment

Peijun Ma, PhD1

Genetic markers for the development of effective therapies to treat bacterial infections

Jeffrey Rybak, PharmD, PhD1 Antifungal pharmacotherapy

Liqin Zhu, PhD1

Stem cells in normal & malignant liver development

Psychology & Biobehavioral Sciences

CHAIR

Kevin Krull, PhD1; Endowed Chair in Psychology

Cognitive neuroscience approaches to outcomes and interventions in pediatric cancer survivors

MEMBERS

Tara Brinkman, PhD1

Psychosocial outcomes of pediatric cancer

Heather Conklin, PhD1

Cognitive outcomes of childhood cancer treatment

Valerie Crabtree, PhD1

Sleep disruptions and fatigue in pediatric oncology

Melissa Hudson, MD1,2; The Charles E. Williams Endowed Chair of Oncology – Cancer Survivorship Health outcomes after childhood cancer

Niki Jurbergs, PhD

Psychological & cognitive impact of pediatric cancer

Sean Phipps, PhD4

ASSOCIATE MEMBERS

Robert Ferguson, PhD

Treatment and rehabilitation of cancer-related cognitive impairment for cancer survivors

Ashley Fournier-Goodnight, PhD, ABPP-CN

Neurobehavioral outcomes in infants and toddlers with early brain pathology

Jennifer Harman, PhD3

Lisa Jacola, PhD

Neurobehavioral outcomes in children treated for cancer

Kendra Parris, PhD

Coping & adjustment in youth with cancer

Jerlym Porter, PhD, MPH1

Transition from pediatric to adult care in sickle cell disease

Brian Potter, PsyD

Neurocognitive outcomes in children with cancer

Megan Wilkins, PhD

Clinical & research psychological services for youth with HIV/AIDS

Victoria Willard, PhD5

ASSISTANT MEMBERS

R. Elyse Heidelberg Kenney, PsyD

Pain and symptom management in pediatric hematology/oncology

Andrew Heitzer, PhD

Neurocognitive outcomes in sickle cell disease

Anna Jones, PhD

Transition off therapy for oncology patients and families

Jennifer Longoria, PhD

Neurocognitive outcomes in sickle cell disease

Nicholas Phillips, MD, PhD

Neurocognitive late effects, cancer survivorship, functional and structural neuroimaging

Darcy Raches, PhD

Acute neurological injury & cognitive outcomes associated with childhood cancer treatment

Katianne Sharp, PhD

Cancer predisposition & adjustment in families of children with cancer

Rachel Webster, PhD

Promotion of healthy lifestyle behaviors in children with cancer & survivors of childhood cancer

INSTRUCTORS

Jessica Cook, PhD

Impact of child–caregiver interactions and caregiver wellbeing on patient psychosocial and medical outcomes

Ryan James, PhD

Pediatric pain and somatic symptoms & trauma-informed care in adolescents and young adults

Radiation Oncology

CHAIR

Thomas Merchant, DO, PhD1;

Baddia J. Rashid Endowed

Chair in Radiation Oncology

Proton radiotherapy for CNS tumors and radiation-related CNS effects

MEMBERS

Chia-ho Hua, PhD

Improving proton therapy accuracy, advanced imaging for radiation therapy, normal tissue complication modeling

Matthew Krasin, MD1

Developing radiation therapy strategies and toxicity profiles for pediatric sarcomas

ASSOCIATE MEMBERS

John Lucas Jr., MS, MD

Brain tumors, neuroblastoma, proton therapy, clinical trial design

Carmen Perez, MD, PHD

Radiation-induced immune responses and to identify radiomitigation strategies

Christopher Tinkle, MD, PhD1

Preclinical evaluation of novel combination therapies and clinical trial development for high-risk brain tumors and sarcomas

ASSISTANT MEMBER

Ozgur Ates, PhD, DABR

Adaptive proton therapy & surface-guided radiation therapy

Structural Biology

CHAIR

Charalampos Kalodimos, PhD1; Joseph Simone Endowed Chair in Basic Research Functional mechanisms of protein machineries

MEMBERS

M. Madan Babu, PhD, FRSC1; George J. Pedersen Endowed Chair in Biological Data Science Data science for discovery and personalized medicine

Scott Blanchard, PhD1; Endowed Chair in Molecular Imaging Examining structure–function relations in macromolecular assemblies

Mario Halic, PhD1

Regulation of genome expression

Richard Kriwacki, PhD1 Structural basis of tumor suppressor function

Tanja Mittag, PhD1

Molecular basis of liquid–liquid phase separation

Junmin Peng, PhD1 Proteomics & metabolomics in human disease

Georgios Skiniotis, PhD; Endowed Chair in Structural Cell Biology

Mechanistic aspects of signal recognition and propagation through G-protein–coupled receptors and their partner proteins

Stephen White, DPhil4

ASSOCIATE MEMBERS

Marcus Fischer, PhD1,2 Protein conformational ensembles

Elizabeth Kellogg, PhD1

Genome engineering, organization, and architecture

ASSISTANT MEMBERS

Christoph Gorgulla, PhD

Development of next-generation methods for computational biology and ligand/drug discovery

Chia-Hsueh Lee, PhD1

Molecular mechanisms of membrane-signaling complexes

Ji Sun, PhD3

ADJUNCT MEMBER

Brenda Schulman, PhD Cellular regulation by ubiquitin-like proteins

Surgery

CHAIR

Andrew Davidoff, MD1; Endowed Chair in Surgical Research

Surgical management of solid tumors, gene therapy, angiogenesis inhibition, neuroblastoma, Wilms tumor

MEMBERS

Bhaskar Rao, MD4

Stephen Shochat, MD4

Martha Wells, DMD, MS

Dental materials and technology utilized in pediatric dentistry

ASSOCIATE MEMBERS

Andrew Murphy, MD1

Renal tumors, neuroblastoma, Wilms tumorigenesis, cancer stem cells

Jun Yang, MD, PhD1

Cancer epigenetics & targeted therapy

ASSISTANT MEMBERS

Abdelhafeez Abdelhafeez, MD3

Lindsay Talbot, MD Sarcomas, immunotherapeutic strategies against sarcoma & solid tumor metastases

ADJUNCT MEMBERS

Mary Ellen Hoehn, MD Pediatric ophthalmology

Paul Klimo Jr, MD Pediatric neurosurgery

Michael Neel, MD Pediatric orthopedic oncology

Anthony Sheyn, MD Pediatric otolaryngology

Matthew Wilson, MD; St. Jude Chair in Pediatric Ophthalmology Pediatric ophthalmology

Tumor Cell Biology

CHAIR

Charles J. Sherr, MD, PhD; Herrick Foundation Endowed Chair in Tumor Cell Biology Tumor suppressor-dependent signaling networks

MEMBERS

Linda M. Hendershot, PhD4

Martine F. Roussel, PhD1; Endowed Chair in Molecular Oncogenesis Genomics & epigenomics in pediatric brain tumors

ASSOCIATE MEMBER Chunliang Li, PhD1

Three-dimensional genome and transcriptional regulation in cancer

Aseem Z. Ansari, PhD

Robert J. Ulrich Endowed Chair in Chemical Biology & Therapeutics

Gregory T. Armstrong, MD, MSCE

Endowed Chair in Epidemiology & Cancer Control

Alessandra d’Azzo, PhD

Jewelers Charity Fund Endowed Chair in Genetics & Gene Therapy

M. Madan Babu, PhD, FRSC

George J. Pedersen Endowed Chair in Biological Data Sciences

Suzanne J. Baker, PhD

Endowed Chair in Brain Tumor Research

Scott C. Blanchard, PhD

Endowed Chair in Molecular Imaging

Joshua Burns, PhD

Jeweler’s Charity Fund Endowed Chair in Cancer Survivorship

Hongbo Chi, PhD

Robert G. Webster Endowed Chair in Immunology

John D. Crispino, PhD, MBA

The Wall Street Committee Endowed Chair

Andrew Davidoff, MD

Endowed Chair in Surgical Research

James R. Downing, MD

Donald Pinkel Endowed Chair in Childhood Cancer Treatment

Michael A. Dyer, PhD

Richard C. Shadyac Endowed Chair in Pediatric Cancer Research

David W. Ellison, MD, PhD

Joan and Roy Gignac Endowed Chair in Pathology and Laboratory Medicine

Richard S. Finkel, MD

George J. Pedersen Endowed Chair in Neurotherapeutics

Patricia M. Flynn, MD

Arthur Ashe Endowed Chair in Pediatric AIDS Research

Amar J. Gajjar, MD

Scott and Tracie Hamilton Endowed Chair in the Brain Tumor Program

Terrence L. Geiger, MD, PhD

St. Jude Endowed Chair in Pediatrics

Stephen M. Gottschalk, MD

Endowed Chair in Bone Marrow Transplantation & Cellular Therapy

Douglas R. Green, PhD

Peter C. Doherty Endowed Chair in Immunology

Andrea L. Gropman, MD

Michael F. Tamer Endowed Chair in Pediatric Neurology

Melissa M. Hudson, MD

The Charles E. Williams Endowed Chair in Oncology–Cancer Survivorship

Charalampos G. Kalodimos, PhD

Joseph Simone Endowed Chair in Basic Research

Thirumala-Devi Kanneganti, PhD

Rose Marie Thomas Endowed Chair in Immunology

Kevin R. Krull, PhD

Endowed Chair in Psychology

Richard E. Lee, PhD

Endowed Chair in Medicinal Chemistry

Peter J. McKinnon, PhD

Endowed Chair in Pediatric Neurological Diseases

Thomas E. Merchant, DO, PhD

Baddia J. Rashid Endowed Chair in Radiation Oncology

James I. Morgan, PhD

Edna & Albert Abdo Shahdam Endowed Chair in Basic Research

Motomi Mori, PhD

Endowed Chair in Biostatistics

Charles G. Mullighan, MBBS(Hons), MD

William E. Evans Endowed Chair

Kirsten Ness, PT, PhD, FAPTA

Endowed Chair in Cancer Survivorship

Ellis J. Neufeld, MD, PhD

John & Lorine Trasher Endowed Chair in Pediatric Medicine

Paul Northcott, PhD

Endowed Chair in Molecular Neuro-Oncology

Alberto S. Pappo, MD

Alvin Mauer Endowed Chair

Julie Park, MD

Endowed Chair in Pediatric Oncology

Ching-Hon Pui, MD

Fahad Nassar Al-Rashid Endowed Chair in Leukemia Research

Octavio Ramilo, MD

Endowed Chair in Infectious Diseases

Charles W.M. Roberts, MD, PhD

Lillian R. Cannon Comprehensive Cancer Center Director Endowed Chair

Carlos Rodriguez-Galindo, MD

Four Stars of Chicago Endowed Chair in International Pediatric Outreach

P. David Rogers, PharmD, PhD

St. Jude Endowed Chair in Pharmaceutical Sciences

Martine F. Roussel, PhD

Endowed Chair in Molecular Oncogenesis

Victor M. Santana, MD

Dr. Charles B. Pratt Endowed Chair in Solid Tumor Research

Charles J. Sherr, MD, PhD

Herrick Foundation Endowed Chair in Tumor Cell Biology

Georgios Skiniotis, PhD

Endowed Chair in Structural Cell Biology

Andrew D. Smith, MD, PhD

Endowed Chair in Diagnostic Imaging (Radiology as of Q3 2024)

Clifford M. Takemoto, MD

Lemuel Diggs Endowed Chair in Sickle Cell Disease

J. Paul Taylor, MD, PhD

Edward F. Barry Endowed Chair in Cell & Molecular Biology

Victor Torres, PhD

Albert and Rosemary Joseph Endowed Chair in Host–Microbe Interactions

Steven M. Varga, PhD

Endowed Chair – Dean St. Jude Children’s Research Hospital Graduate School of Biomedical Sciences

Mitchell J. Weiss, MD, PhD

Arthur Nienhuis Endowed Chair in Hematology

Jun J. Yang, PhD

Endowed Chair in Pharmacogenomics

Jinghui Zhang, PhD

Endowed Chair in Bioinformatics

Postdoctoral Fellows

Diana Acevedo, PhD, Developmental Neurobiology

Anushree Achari, PhD, Chemical Biology & Therapeutics

Srijan Acharya, PhD, Pharmacy & Pharmaceutical Sciences

Sarada Achyutuni, PhD, Pathology

Adeleye Adeshakin, PhD, Bone Marrow Transplantation & Cellular Therapy

Himanshi Agarwal, PhD, Pathology

Farhan Ahmad, PhD, Center of Excellence - Leukemia Studies

Jemil Ahmed, PhD, Computational Biology

Shahbaz Ahmed, PhD, Structural Biology

Shelby Anderson, PhD, Chemical Biology & Therapeutics1

Konstantin Andreev, PhD, Host–Microbe Interactions

Hiroyasu Aoki, PhD, Host–Microbe Interactions

Amir Arabzade, PhD, Developmental Neurobiology

Cassie Argenbright, PhD, Psychology & Biobehavioral Sciences

Aahan Arif, PhD, Radiation Oncology

Emilia Asante, PhD, Strategic Communication, Education & Outreach

Anoop Babu Vasandan, PhD, Immunology

Lu Bai, PhD, Immunology

Seamus Balinth, PhD, Cancer Center Administration

Juan Barajas, PhD, Pathology

Stefanie Baril, PhD, Pharmacy & Pharmaceutical Sciences

Aditya Barve, PhD, Hematology

Jake Batchelder, PhD, Structural Biology1

Katelyn Baumer, PhD, Chemical Biology & Therapeutics1

Swarna Beesetti, PhD, Cell & Molecular Biology/Immunology 2

Numair Belgaumi, PhD, Global Pediatric Medicine

Declan Bennett, PhD, Computational Biology

Soumen Bera, PhD, Hematology

Amy Berkman, MD, Oncology

Wyatt Beyers, PhD, Cell & Molecular Biology

Akash Bhaskar, PhD, Pharmacy & Pharmaceutical Sciences

Akshita Bhatt, PhD, Developmental Neurobiology1

Kashi Bhattarai, PhD, Pharmacy & Pharmaceutical Sciences

Khaggeswar Bheemanapally, PhD, Structural Biology1

Weixiang Bian, PhD, Immunology

Caitlin Billiot, PhD, Infectious Diseases

Ramya Billur, PhD, Cell & Molecular Biology

Wade Borcherds, PhD, Structural Biology2

Austin Boucher, PhD, Hematology

Ryan Brady, PhD, Structural Biology2

Helena Brenes, MD, Infectious Diseases

David Brice, PhD, Host–Microbe Interactions

Pam Brigleb, PhD, Host–Microbe Interactions

Mark Brimble, PhD, Host–Microbe Interactions

John Bryant, PhD, Structural Biology

Ratnakar Bynigeri, PhD, Immunology1

Donghong Cai, PhD, Pathology

Zhongheng Cai, PhD, Biostatistics

Victoria Castro, PhD, Developmental Neurobiology

Kasturee Chakraborty, PhD, Diagnostic Imaging2,5

Saikat Chakraborty, PhD, Oncology

Bappaditya Chandra, PhD, Structural Biology1

Chih-Chiang Chang, PhD, Diagnostic Imaging1,5

Alexandra Chasse, PhD, Infectious Diseases

Kanokporn Chattrakun, PhD, Structural Biology

Letitia Chen, PhD, Host–Microbe Interactions

Wen Chen, PhD, Immunology

Xin-yan Chen, PhD, Tumor Cell Biology

Yantao Chen, PhD, Oncology

Peter Chockley, PhD, Bone Marrow Transplantation & Cellular Therapy

Jaesung Choi, PhD, Epidemiology & Cancer Control

Sk Mohiuddin Choudhury, PhD, Immunology

Mengqi Chu, PhD, Structural Biology

Chia-Lung Chuang, PhD, Developmental Neurobiology

Mellisa Clemons, PhD, Developmental Neurobiology

Jordan Cockfield, PhD, Oncology

Lisett Contreras, PhD, Pathology

Adam Cornwell, PhD, Hematology

Aaron Cruz Navarrete, PhD, Structural Biology

Chenxi Cui, PhD, Structural Biology1

Preeti Dabas, PhD, Chemical Biology & Therapeutics2

Jonathan Dabbs, PhD, Diagnostic Imaging5

Adithi Danda, PhD, Chemical Biology & Therapeutics

Tram Dao, PhD, Bone Marrow Transplantation & Cellular Therapy

Anuska Das, PhD, Structural Biology

Jitendra Das, PhD, Structural Biology

Tapojyoti Das, PhD, Structural Biology

Abhijit Dasgupta, Structural Biology1

Amy Davis, PhD, Infectious Diseases

Ian Delahunty, PhD, Oncology

Ashish Deshmukh, PhD, Structural Biology

Subhash Dhital, PhD, Cell & Molecular Biology

Thi Duyen Do, MD, Computational Biology

Esteban Dodero Rojas, PhD, Structural Biology

Priyanka Dogra, PhD, Structural Biology

Laura Doorley, PhD, Pharmacy & Pharmaceutical Sciences

Melodie Doute, PhD, Hematology

James Du, PhD, Structural Biology

Asaf Elazar, PhD, Structural Biology

Rebekah Eleazer, PhD, Oncology

Abdelrahman Elsayed, PhD, Biostatistics

Sally Elshaer, PhD, Oncology1

Carolin Escherich, MD, Pharmacy & Pharmaceutical Sciences1

Mansoore Esmaili, PhD, Structural Biology1

Tiffany Eulalio, PhD, Epidemiology & Cancer Control

Li Fan, PhD, Computational Biology

Esmat Fathi, PhD, Cell & Molecular Biology

Feng Feng, PhD, Developmental Neurobiology

Carlos Fernandez Pena Acuna, PhD, Developmental Neurobiology2

Michelle Fernando, PhD, Developmental Neurobiology

David Filipovic, PhD, Developmental Neurobiology

Leigh Fremuth, PhD, Genetics

Jennifer French, PhD, Epidemiology & Cancer Control

Kaustav Gangopadhyay, PhD, Structural Biology

Pritha Ganguly, PhD, Structural Biology

Karishma Gangwani, PhD, Computational Biology2

Megha Garg, PhD, Pharmacy & Pharmaceutical Sciences

Dusan Garic, PhD, Developmental Neurobiology

Mohamed Ghonim, PhD, Host–Microbe Interactions1

Aritra Ghosal, PhD, Biostatistics

Kyla Gibney, PhD, Psychology & Biobehavioral Sciences

Milica Gilic, PhD, Structural Biology

Prashant Giri, PhD, Immunology

Bryan Glazer, PhD, Chemical Biology & Therapeutics

Vanshita Goel, PhD, Tumor Cell Biology

Luisa Gomez Londono, PhD, Pharmacy & Pharmaceutical Sciences1

Abigail Gondringer, PhD, Chemical Biology & Therapeutics

Chelsea Goodenough, PhD, Epidemiology & Cancer Control

Xinrui Gui, PhD, Structural Biology

Omer Gullulu, PhD, Structural Biology1

Xuanming Guo, PhD, Immunology1

Yifeng Guo, PhD, Computational Biology

Samantha Hack, PhD, Cell & Molecular Biology

Priyanka Halder, PhD, GMP1

Eric Hall, PhD, Cell & Molecular Biology1

Trent Hall, PhD, Hematology

Liam Hallada, PhD, Developmental Neurobiology

Rawan Hammoud, MD, Epidemiology & Cancer Control1

Xiaolei Hao, PhD, Immunology

Yanhong Hao, PhD, Structural Biology

Walter Harrington, PhD, Host–Microbe Interactions

Minghong He, PhD, Immunology1

Elodie Henriet, PhD, Oncology

Taylor Hibler, PhD, Host–Microbe Interactions

Siarhei Hladyshau, PhD, Computational Biology

Cyrielle Holuka, PhD, Oncology

Jack Hopkins, PhD, Oncology

Madeline Horan, PhD, Epidemiology & Cancer Control1

Keito Hoshitsuki, PharmD, Pharmacy & Pharmaceutical Sciences1

Hadi Hosseini, PhD, Biostatistics/ Computational Biology/Structural Biology1

Ruida Hou, PhD, Pharmacy & Pharmaceutical Sciences

Maowei Hu, PhD, Chemical Biology & Therapeutics

Wenjun Huang, PhD, Immunology

Ya Huang, PhD, Structural Biology

Yan Huang, PhD, Structural Biology2

Yuanyuan Huang, PhD, Hematology

Brydie Huckestein, PhD, Host–Microbe Interactions

Michael Hughes, PhD, Cell & Molecular Biology

Jihye Hwang, PhD, Computational Biology

Jongchan Hwang, PhD, Oncology

Omkar Indari, PhD, Immunology

Siri Manasa Ippagunta, PhD, Developmental Neurobiology

Katelyn Jackson, PhD, Structural Biology

Laura Jamrog, PhD, Hematology

Thilina Jayasinghe, PhD, Chemical Biology & Therapeutics

Bohyeon Jeong, PhD, Developmental Neurobiology

Fubo Ji, PhD, Immunology1

Meiqin Jiang, PhD, Structural Biology1

Menglin Jiang, PhD, Immunology

Yanbo Jiang, PhD, Developmental Neurobiology

Kasey Jividen, PhD, Hematology2

Minjeong Jo, PhD, Structural Biology

Cydney Johnson, PhD, Host–Microbe Interactions

Jordan Johnson, PhD, Bone Marrow Transplantation & Cellular Therapy

Amber Jones, PhD, Bone Marrow Transplantation & Cellular Therapy

Kamal Jouad, PhD, Diagnostic Imaging1,5

Seunghyun Jung, PhD, Developmental Neurobiology1

Ahmed Kandeil, PhD, Host–Microbe Interactions

Suresh Kandikonda, PhD, Chemical Biology & Therapeutics1

Tae Gun Kang, PhD, Immunology

Priyanka Karmokar, PhD, Surgery

Sara Kassel, PhD, Oncology

Mangesh Kaulage, PhD, Chemical Biology & Therapeutics

Sukhmanjit Kaur, PhD, Bone Marrow Transplant & Cellular Therapy

Ahmed Khalaf, PhD, Hematology1

Suparna Khatun, PhD, Structural Biology

Hanane Khoury, PhD, Hematology

Jiyeon Kim, PhD, Immunology

Yoonji Kim, PhD, Epidemiology & Cancer Control

Shunsuke Kimura, PhD, Pathology1

Evan Kingsley, PhD, Developmental Neurobiology1

Kaitlin Koreski, PhD, Cell & Molecular Biology

Lili Kotmayer, MD, Hematology

Damian Krzyzanowski, PhD, Hematology

Aditya Kshirsagar, PhD, Spatial Transcriptomics Core1

Abhishek Kumar, PhD, Structural Biology1

Harsh Kumar, PhD, Cell & Molecular Biology

Prasanth Kumar, PhD, Immunology

Jesyin Lai, PhD, Diagnostic Imaging1,5

Xin Lan, PhD, Immunology1

Su Hyun Lee, PhD, Oncology

Dongfang Li, PhD, Cell & Molecular Biology2

Hanxia Li, PhD, Computational Biology

Miaomiao Li, PhD, Radiation Oncology

Siyu Li, PhD, Structural Biology

Zhenrui Li, PhD, Immunology

Chun-Yang Lin, PhD, Computational Biology

Jennapher Lingo VanGilder, PhD, Radiation Oncology

Danielle Little, PhD, Developmental Neurobiology

Beiyun Liu, PhD, Immunology

Fengming Liu, PhD, Developmental Neurobiology1

Jiaqi Liu, PhD, Pathology

Ke Liu, PhD, Pharmacy & Pharmaceutical Sciences1

Qiang Liu, PhD, Pharmacy & Pharmaceutical Sciences

Xueying Liu, PhD, Computational Biology

Yun Liu, PhD, Immunology

Zhaolin Liu, PhD, Cell & Molecular Biology

Nele Loecher, PhD, Psychology & Biobehavioral Sciences

Jianlin Lu, I PhD, mmunology

Joelle Magne, PhD, Immunology1

Arun Maharaj, PhD, Epidemiology & Cancer Control1

Kelsey Maher, PhD, Computational Biology

Maud Maillard, PhD, Pharmacy & Pharmaceutical Sciences1

Snigdha Maiti, PhD, Structural Biology

Efren Maldonado, PhD, Chemical Biology & Therapeutics1

Deepshikha Malik, PhD, Structural Biology

Alexandra Mandarano, PhD, Infectious Diseases

Mohammad Amin Mannan, PhD, Pharmacy & Pharmaceutical Sciences

Luigi Mari, PhD, Immunology

Maxwell Martin, PhD, Structural Biology2

Masihuzzaman, PhD, Structural Biology

Yurika Matsui, PhD, Developmental Neurobiology

Taylor Matte, PhD, Developmental Neurobiology

Eli McDonald, PhD, Structural Biology

Johanna Melo-Cardenas, PhD, Hematology1

Smrithi Menon, PhD, Host–Microbe Interactions

Audrey Mercier, PhD, Tumor Cell Biology

Robert Mettelman, PhD, Immunology

Bisi Miao, PhD, Pathology

Nicole Michmerhuizen, PhD, Pathology

Benjamin Minden-Birkenmaier, PhD, Developmental Neurobiology

Anastasia Minervina, PhD, Host–Microbe Interactions

Akhilesh Mishra, PhD, Computational Biology1

Priya Mittal, PhD, Oncology1

Mohammad Ali Mohammad Nezhady, PhD, Oncology

Jyotirmoy Mondal, PhD, Chemical Biology & Therapeutics

Lindsey Montefiori, PhD, Pathology2

Dorothea Morris, PhD, Host–Microbe Interactions

Janeala Morsby, PhD, Oncology

Tresor Mukiza, PhD, Cell & Molecular Biology

Bharath Muralikrishnan, PhD, Cell & Molecular Biology1

Saikat Nandy, PhD, Biostatistics

Ambuja Navalkar, PhD, Structural Biology1

Miguel Navarrete, PhD, Psychology & Biobehavioral Sciences

Stephany Navarro, PhD, Host–Microbe Interactions

Madeline Niederkorn, PhD, Hematology

Andrew Nishimoto, PhD, Host–Microbe Interactions

Kelsey North, PhD, Developmental Neurobiology

Jessica Nunes, PhD, Hematology

Greisly Nunez, PhD, Immunology

Shaikh Nurunnabi, PhD, Developmental Neurobiology

Dora Obodo, PhD, Biostatistics

Jennifer Ocasio Adorno, PhD, Research Education & Training Grant Support

Mary Cameron Ogg, PhD, Developmental Neurobiology

Faten Okda, DVM, PhD, Host–Microbe Interactions

Elisabet Olsen, PhD, Oncology

Han Wee Ong, PhD, Chemical Biology & Therapeutics

Eda Ozdemir, PhD, Host–Microbe Interactions

Tanya Paes, PhD, Psychology & Biobehavioral Sciences

Anasuya Pal, Chemical Biology & Therapeutics

Pankaj Pandey, PhD, Diagnostic Imaging5

Shubhant Pandey, PhD, Center for Pediatric Neurological Disease Research

Nagakannan Pandian, PhD, Immunology

Jung-Un Park, PhD, Structural Biology1

Seong Guk Park, PhD, Structural Biology

Christopher Patton, PhD, Host–Microbe Interactions1

Mary Patton, PhD, Developmental Neurobiology

Jing Pei, PhD, Cell & Molecular Biology

Shalmali Pendse, PhD, Hematology

Shashika Perera, PhD, Diagnostic Imaging5

Charles Perry, PhD, Developmental Neurobiology

Kateryna Petrykey, PhD, Epidemiology & Cancer Control

Sarayut Phasuk, PhD, Developmental Neurobiology

Adam Pickrum, PhD, Host–Microbe Interactions

Shabareesh Pidathala, PhD, Structural Biology

Anna Pittman, PhD, Developmental Neurobiology

Noel-Marie Plonski, PhD, Epidemiology & Cancer Control

Petri Polonen, PhD, Pathology

Pragya Poudel, PhD, HPV Cancer Prevention

Manisha Poudyal, PhD, Cell & Molecular Biology

Rojalin Pradhan, PhD, Cell & Molecular Biology

Rachel Prescott, PhD, Host–Microbe Interactions

Sashikantha Reddy Pulikallu, PhD, Structural Biology

Qiang Qin, PhD, Immunology

Zhuo Qu, PhD, Biostatistics1

Sabina Ranjit, PhD, Pharmacy & Pharmaceutical Sciences2

Meghdad Razizadeh, PhD, Developmental Neurobiology

Tyler Ripperger, PhD, Host–Microbe Interactions

Karen Ritter, PhD, Oncology

Sarah Robinson-Thiewes, PhD, Chemical Biology & Therapeutics

Stephanie Rockfield, PhD, Cell & Molecular Biology

Sarayu Row, PhD, Cell & Molecular Biology2

Sourav Roy, PhD, Chemical Biology & Therapeutics

Diana Sa da Bandeira, PhD, Hematology

Sushree Sahoo, PhD, Hematology

Julio Sanchez, PhD, Structural Biology

Laura Sanchez, PhD, Diagnostic Imaging1,5

Andrea Sanchez Corzo, PhD, Diagnostic Imaging1,5

Darian Santana, PhD, Pharmacy & Pharmaceutical Sciences

Gustavo Santiago-Collazo, PhD, Host–Microbe Interactions

Roman Sarkar, PhD, Immunology

Neha Sarodaya, PhD, Developmental Neurobiology

Jieun See, PhD, Developmental Neurobiology

Anna Seffernick, PhD, Biostatistics1

Justin Seffernick, PhD, Chemical Biology & Therapeutics

Jeremy Shaw, PhD, Immunology

Noha Shendy, PhD, Oncology1

Him Shrestha, PhD, Structural Biology

Rupesh Shrestha, PhD, Chemical Biology & Therapeutics1

Sauradeep Sinha, PhD, Bone Marrow Transplantation & Cellular Therapy

Oleksandra Sirozh, PhD, Structural Biology1

Adam Smiley, PhD, Structural Biology

Maria Smith, PhD, Host–Microbe Interactions

Hao Song, PhD, Immunology

Xirui Song, PhD, Bone Marrow Transplantation & Cellular Therapy

Jiao Sun, PhD, Biostatistics

Julianna Sun, PhD, Developmental Neurobiology

Renqiang Sun, PhD, Immunology

Xiang Sun, PhD, Immunology

Balamurugan Sundaram, PhD, Immunology

Luka Svet, PhD, Host–Microbe Interactions

Jeffrey Swan, PhD, Structural Biology1

Shannon Sweeney, PhD, Developmental Neurobiology

Kumari Sweta, PhD, Chemical Biology & Therapeutics

Kasia Szoltysek, PhD, Pathology

Meng Tang, PhD, Structural Biology

Justin Tanner, PhD, Psychology & Biobehavioral Sciences

Roshina Thapa, PhD, Oncology

Kristen Thomas, PhD, Developmental Neurobiology2

Sai Thulabandu, PhD, Developmental Neurobiology

Cheng Tian, PhD, Pharmacy & Pharmaceutical Sciences

Bailey Tibben, PhD, Pharmacy & Pharmaceutical Sciences1

Ricky Tirtakusuma, PhD, Host–Microbe Interactions

Kyla Tooley, PhD, Developmental Neurobiology

Carolina Torres Rojas, PhD, Diagnostic Imaging5

Despoina Trasanidou, PhD, Hematology1

Olivia Travis, PhD, Developmental Neurobiology

Alexandra Trevisan, PhD, Developmental Neurobiology

Sanja Trifkovic, PhD, Host–Microbe Interactions1

Uwemedimo Udoh, MD, PhD, Cell & Molecular Biology

Masayuki Umeda, MD, Pathology

Saurabh Upadhyay, PhD, Immunology1

Gintvile Valinciute, PhD, Tumor Cell Biology

Alanna Van Huizen, PhD, Hematology

Diego Velasquez Pulgarin, PhD, Hematology

Niveda Vellore, PhD, Hematology

Ashish Verma, PhD, Chemical Biology & Therapeutics

Kaitlin Victor, PhD, Bone Marrow Transplantation & Cellular Therapy

Paulina Villanueva, PhD, Diagnostic Imaging1,5

Eirinaios Vrettos, PhD, Chemical Biology & Therapeutics

Fnu Wahiduzzaman, PhD, Structural Biology

LaShanale Wallace, PhD, Oncology

Haolan Wang, MD, Structural Biology

Jingheng Wang, PhD, Chemical Biology & Therapeutics2

Ju Wang, PhD, Structural Biology

Kaili Wang, PhD, Pathology

Liang Wang, PhD, Structural Biology

Xiao Cui Wang, PhD, Structural Biology

Yan Wang, PhD, Immunology

Yaqiu Wang, PhD, Immunology

Abubakar Wani, PhD, Immunology

Grace Ward, PhD, Immunology

Meghan Ward, PhD, Bone Marrow Transplantation & Cellular Therapy

Megan Ware, PhD, Epidemiology & Cancer Control1

Zoe Watson, PhD, Structural Biology

Jayce Weesner, PhD, Genetics

Griffin Welfer, PhD, Structural Biology

Elizabeth Wickman, PhD, Bone Marrow Transplantation & Cellular Therapy

Kristin Wiggins, PhD, Surgery

Shyra Wilde, PhD, Host–Microbe Interactions

Andrew Willems, PhD, Computational Biology

Laura Wilt, PhD, Chemical Biology & Therapeutics2

Stephen Winston, PhD, Surgery

Tristen Wright, PhD, Developmental Neurobiology

Chengzhou Wu, PhD, Biostatistics

Jinjun Wu, Cell & Molecular Biology

Qiong Wu, PhD, Surgery2

Stephanie Wu, PhD, Developmental Neurobiology

Hui Xia, PhD, Immunology

Benjin Xu, PhD, Structural Biology

Lu Xu, PhD, Imaging Sciences

Lucy Xue, PhD, Host–Microbe Interactions

Chao Yang, PhD, Surgery

Jifeng Yang, PhD, Tumor Cell Biology

Jiyuan Yang, PhD, Computational Biology

Ke Yang, PhD, Hematology

Shu Yang, PhD, Structural Biology1

Zemin Yang, PhD, Scientific Director Office

Xiangyu Yao, PhD, Computational Biology

Jay Yarbro, PhD, Structural Biology

Rajesh Yetirajam, PhD, Pharmacy & Pharmaceutical Sciences

Siqi Yi, PhD, Hematology

Masanori Yoshida, MD, PhD, Hematology

Tomoko Yoshida, MD, PhD, Epidemiology & Cancer Control

Satoshi Yoshimura, PhD, Pharmacy & Pharmaceutical Sciences

Zhiyuan You, PhD, Immunology

Alexander Young, PhD, Immunology

Sarah Young, PhD, Chemical Biology & Therapeutics

Zehui Yu, DVM, Pharmacy & Pharmaceutical Sciences

Sujing Yuan, PhD, Immunology

Ugur Yurtsever, PhD, Cell & Molecular Biology Nan Zhang

Fatima Zaidi, PhD, Structural Biology

Nan Zhang, PhD, Structural Biology

Xiaohong Zhang, PhD, Immunology1

Xiaoyu Zhang, PhD, Immunology

Xue Zhang, PhD, Structural Biology

Yifan Zhang, PhD, Chemical Biology & Therapeutics

Yuhan Zhang, PhD, Structural Biology

Huanbin Zhao, PhD, Pharmacy & Pharmaceutical Sciences

Lanying Zhao, PhD, Hematology

Tuyu Zheng, PhD, Developmental Neurobiology

Clinical Fellows

Immunocompromised Children & Adolescents Fellow

Lisa Hiskey, DO3

Infectious Diseases Fellows

Afreen Abraham, MBBS

Elspeth Bittle, MD

Sandra Castejon Ramirez, MD

Hayley Scheerer, MD

Kate Shapiro, MD

Neuropsychology Fellows

Lakia Kearson, PhD1

Bethany Schwandt, PhD

Alicia Travis

Ocular Oncology Fellow

William Evans, MD

Pediatric Hematology-Oncology Fellows

Margaret Cupit-Link, MD1

La’Ron Browne, MD

Stephanie Gehle, MD

Vidyasagar Jaiswal, MBBS, MPH1

Megan Lilley, MD

Ryan Lion, MD

Grace McKay-Corkum, MD

Margit Mikkelsen, MD

Bradley Muller, MD2

Sarah Mumanachit, MD

Devin Murphy, MD

Trisha Paul, MD

Katelyn Purvis, MD

Matthew Rees, MD3

Supriya Sarvode, MD3

Jasmine Smith, MD2

Alexandra Superdock, MD

Shruthi Suryaprakash, MD

Marleni Torres Nunez, MD

Pediatric Hematology-Oncology/ Adult Hematology Fellow

Tarun Aurora, MD1

Peipei Zhou, PhD, Immunology1

Qi Zhou, PhD, Surgery

Xuelin Zhou, PhD, Structural Biology

Changlei Zhu, PhD, Chemical Biology & Therapeutics

Hanwen Zhu, PhD, Structural Biology1

Jingwen Zhu, PhD, Pharmacy & Pharmaceutical Sciences

Mingrui Zhu, PhD, Computational Biology

Jaquelyn Zoine, PhD, Bone Marrow Transplantation & Cellular Therapy

Pediatric Surgery Oncology Fellows

Huma Faize Halepota, MBBS1

Zachary Morrison, MD

Pharmacy Infectious Diseases Fellow

Thanh Pham, PharmD1

Pharmacy Informatics Fellow

Nicholas Jantrakul, PharmD1

Pharmacy Oncology Fellows

Milre Matherne, PharmD4

Megan Wright, PharmD2

Pharmacogenomics Fellow

Kayla Thibodaux, PharmD1

Psychology Fellow

Emily Bernstein, MS1

Sickle Cell Disease Fellow

Khalid Elbashir, MBBS

Graduate Students

St. Jude Graduate Students

Grace Adkins, Oncology

Korede Akindele, BH, Global Child Health

Victoria Akingbehin

Margaret Alexander

Khaled Al Habiba, RN, MSHA, Global Child Health

Zahangir Alom PhD, Clinical Investigations

Cassie Argenbright, PhD, Clinical Investigations

Tarun Aurora, MD, Clinical Investigations1

Tamar Bar Ziv

Ronnie Baticulon, MD, Global Child Health

Miguel Bayona, MD, MPPC, Global Child Health

Swarna Beesetti, PhD, Clinical Investigations

Bonn Belingon, Pharmacy & Pharmaceutical Sciences

Amy Berkman, MD, Clinical Investigations

Elspeth Bittle, MD, Clinical Investigations1

Mollie Black, Host–Microbe Interactions

Jordan Bondrowski

Alexandra Boyd, RN, Clinical Investigations

Jennyfer Bran, MD, Clinical Investigations

Joseph Brett, Structural Biology

Bailey Bridgers

Brett Brown

Kaitlin Budd, Developmental Neurobiology

Ashlyn Bugbee, Infectious Diseases

Taylor Bugbee, Developmental Neurobiology

Terri Cain, Oncology

Sandra Castejon Ramirez, MD, Clinical Investigations

Omar Chamdine, MD, Global Child Health

Jemma Clary

Sophie Cochiolo

Kristine Crews, PharmD, Clinical Investigations

Margaret Cupit-Link, MD, Clinical Investigations1

David Dachille, Immunology

Christina Daly, Cell & Molecular Biology4

Morgan Davis, Host–Microbe Interactions

Yogesh Dhungana, Computational Biology

Yuliana Diaz Tirado

Diana Dinh, Bone Marrow Transplantation & Cellular Therapy

Liezl Du Plessis, MD, MMD, Global Child Health1

Marygrace Duggar, Immunology

Christine Dunn, Host–Microbe Interactions

Angela Edwards, BHS, RT Clinical Investigations1

Mahmoud Elzembely, MD, Global Child Health

Nadine Emil

Mark Engelken

Rebecca Epperly, MD, Clinical Investigations1

Lauren Ezzell, Pathology

Mahwish Faizan, MBBS, Global Child Health

Arika Feils, Bone Marrow Transplantation & Cellular Therapy

Diego Figueredo, MD, Global Child Health

Abigail Fish, Chemical Biology & Therapeutics

Matthew Fisher

Teresa Fonseca, MD, MS, Global Child Health

Jake Friske, Tumor Cell Biology

Jessica Gaevert, Immunology

Lily Saladana Gallo, MD, Global Child Health1

Chelsea Goodenough, PhD, Clinical Investigations

Oliver Grants-Champman, Cell & Molecular Biology

Liam Hallada, Developmental Neurobiology4

Rawan Hammoud, MD, Clinical Investigations

Katie Han, Developmental Neurobiology

Lane Hartman

Sarah He

Blake Holcomb, Developmental Neurobiology

Job Huxford, Cell & Molecular Biology

Taiye Ibiyeye, MBBS, FMCS, FWACS, Global Child Health

Alissa Jackson, Hematology

Matthew Kieffer, Developmental Neurobiology

Sandra Kietlinska, Oncology

Aimee Kissou, MD, Global Child Health

Francine Kouya, MD, Global Child Health

Christy LaFlamme, Cell & Molecular Biology

Randolph Larsen, Oncology

Megan Lilley, MD, Clinical Investigations

Fuentes Lucia, MSc, Global Child Health

Zamokuhle Magagula, RN, BA, Global Child Health

JaQuel Maise, Oncology

Nidhi Mali, PhD, Clinical Investigations

Hayden Malone, Oncology

Milre Matherne, PharmD, Clinical Investigations

Aaron Mayo, Hematology

Ashton McKinnon, Infectious Diseases

Sanya Mehta, Bone Marrow Transplantation & Cellular Therapy

Vanessa Meza-Perez, Pharmacy & Pharmaceutical Sciences

Ramon Misla David, Center for Pediatric Neurological Disease Research

Erika Montalvo, MD, Global Child Health

Pablo Gonalez Montalvo, MD, Global Child Health1

Sarah Moore, Bone Marrow Transplantation & Cellular Therapy

Brendan Morrow, Host–Microbe Interactions

Mariam Ndagire, RN, Global Child Health1

Uma Neelakantan, Structural Biology

Adriana Ramirez Negron1

Amon Ngongola, MD, Global Child Health

Erienne Norton, Immunology

Hovaire Nsabimana, MD, Global Child Health1

Kiera O’Keefe, Hematology

Athena Olszewski, Center for Pediatric Neurological Diseases Research

Vivian Paintsil, MB, CHB, MSc, Global Child Health

Gabrielle Papp, Chemical Biology & Therapeutics

Claudia Pascual Morales, MD, Global Child Health1

Trevor Penix, Infectious Diseases

Nicolas Peterson, Immunology

Gregory Phelps, Chemical Biology & Therapeutics4

Soniya Pinto, MBBS, Clinical Investigations

Brittany Pioso, Structural Biology

Bilal Qureshi, MBBS, FCPS, Global Child Health1

Parul Rai, MD, Clinical Investigations

Revathi Rajagopal, MD, MMed, Global Child Health1

Auburn Ramsey

Isaiah Reeves, Surgery1

Logan Rice, Host–Microbe Interactions

Jordan Roach, Developmental Neurobiology

Lauren Rosenthal1

Samuel Rovito, Infectious Diseases

Kincaid Rowbotham, Structural Biology

Lauren Rowland, Infectious Diseases

Nihad Salifu, MBChB, Global Child Health

Austin Santhin, Infectious Diseases

Hayley Scheerer, MD, Clinical Investigations

Kate Shapiro, MD, Clinical Investigations

Sarah Sherman, Structural Biology

Jamaica Siwak, Cell & Molecular Biology

Jordan Skorupa, Oncology

Hannah Snoke, Chemical Biology & Therapeutics

Matthew So, Immunology

Bradley Stevens, Oncology

Morgan Sutton, Bone Marrow Transplantation & Cellular Therapy1

Shannon Sweeney, PhD, Clinical Investigations

Marta Zapata Tarres, MD, PhD Global Child Health

Robert Teis, Bone Marrow Transplantation & Cellular Therapy

Kim Hoa Nguyen Thi, MD, Global Child Health

Vinh Truong, Structural Biology

Sucharita Tuladhar, MD, MBBS, Global Child Health

Samantha Turk, Developmental Neurobiology

Carmen Uscatu, BSc, Global Child Health

Elena Valencia-Barbosa, Clinical Investigations

Holly Van Epps, Clinical Investigations

Dennis Voronin, Cell & Molecular Biology

Kyna Vuong, Oncology

Christina Wang, Cell & Molecular Biology

Nicholas Watkins, MD, Clinical Investigations

Kendall Whitt, Infectious Diseases

Elizabeth Wickman, Bone Marrow Transplantation & Cellular Therapy1

Kristin Wiggins, Infectious Diseases4

Benjamin Wilander, Immunology1

McLean Williamson, Hematology

Stephen Winston, Surgery1

Tristen Wright, Cell & Molecular Biology4

Milugeta Yimer, MD, Global Child Health1

Whitney Ziegenhorn, MD, Clinical Investigations

External Graduate Students

Osama Alaidi, Chemical Biology & Therapeutics

Amir Arabzade, Developmental Neurobiology4

Richard Begyinah, Chemical Biology & Therapeutics

Lauren Brakefield, Cell & Molecular Biology

Jingjing Chen, Hematology

Ashton Coker, Chemical Biology & Therapeutics

Andrew Cortes, Surgery

Erielle Culp, Computational Biology

Amy Davis, Infectious Diseases

Laura Doorley, Pharmacy & Pharmaceutical Sciences4

Ashley Gray, Pharmacy & Pharmaceutical Sciences

Ethan Hill, Diagnostic Imaging

Umamah Iram, Developmental Neurobiology

Alexander Jenner, Chemical Biology & Therapeutics

Menglin Jiang, Immunology4

Alisha Kardian, Developmental Neurobiology

William Kuenzinger, Developmental Neurobiology

Genevieve Lambert, Epidemiology & Cancer Control

Jimin Lee, Developmental Neurobiology

Song-Eun Lim, Computational Biology

Chun-Yang Lin, Immunology4

Michaela Meehl, Immunology

Joseph Miller, Pharmacy & Pharmaceutical Sciences

Kumar Niloy, Pharmacy & Pharmaceutical Sciences

Allison Norman, Immunology

Schyler Odum, Chemical Biology & Therapeutics

Homa Rezaei, Chemical Biology & Therapeutics

Christopher Rogers, Hematology

Dewan Shrestha, Hematology4

Utsav Shrestha, Diagnostic Imaging

Deryn St. James, Host–Microbe Interactions

Sadie Walker, Center for Advanced Genome Engineering

Jinjun Wu, Cell & Molecular Biology4

Zhen Xie, Computational Biology

Jingwen Zhu, Pharmacy & Pharmaceutical Sciences4

2024 Board of Governors

These volunteers served on the Board of Governors of St. Jude Children’s Research Hospital during 2024. Officers are indicated by the titles under their names.

Board of Governors

Joyce A. Aboussie

Steven J. Allen MD

Joseph S. Ayoub Jr.

Paul J. Ayoub

Frederick M. Azar, MD

Martha Perine Beard

Robert A. Breit, MD1

Terry L. Burman

Lisa R. Diller, MD

James R. Downing, MD2

St. Jude President and CEO

Joseph E. Eid, MD

John D. Farina Jr.3

Fred P. Gattas III, PharmD

Judy A. Habib

Chair

Gabriel G. Haddad, MD

Vice Chair

Charles C. Hajjar

Fouad M. Hajjar, MD

Frederick R. Harris Jr., MD

Secretary

Carla Z. Hassan3

J. David Karam II

Scott A. Kupor

Katherine N. Lapp3

Sharon L. McCollam

Samia Melhem

Robert T. Molinet

Neela M. Montgomery

Ramzi N. Nuwayhid

Thomas J. Penn III

Christina M. Rashid

Kathryne G. Reeves

Camille F. Sarrouf Jr.

Aarti S. Shah2

Richard C. Shadyac Jr.2

Joseph C. Shaker1

Joseph G. Shaker

George A. Simon II

Michael C. Simon

Tony Thomas

Paul H. Wein1

Tama H. Zaydon

Emeritus Members

Thomas G. Abraham

Susan Mack Aguillard, MD

Mahir R. Awdeh

James B. Barkate

Jack A. Belz4

Sheryl A. Bourisk

Stephen J. Camer, MD

Ann M. Danner

George Elias Jr.

Hasan M. Elkhatib

Fred P. Gattas Jr.

Ruth C. Gaviria

Christopher B. George, MD

Paul K. Hajar

Sam F. Hamra

Frederick R. Harris

Bruce B. Hopkins

Richard J. Karam

Salli E. LeVan

Paul J. Marcus

Michael D. McCoy

James O. Naifeh

Talat M. Othman4

Manal B. Saab

Frederick W. Smith4

Ronald A. Terry4

Terre Thomas

Pat Kerr Tigrett

Richard M. Unes

Thomas C. Wertz

Robert P. Younes, MD

Ramzi T. Younis, MD

Leah J. Domitrovic

Chief Governance Officer/ Corporate Secretary

2024 Executive Committee

James R. Downing, MD, Chair

President and Chief Executive Officer

Aseem Z. Ansari, PhD

Chair, Chemical Biology & Therapeutics

Gregory T. Armstrong, MD, MSCE

Chair, Epidemiology & Cancer Control Oncology

M. Madan Babu, PhD, FRSC

Director, Center of Excellence for Data Driven Discovery

Structural Biology

Suzanne J. Baker, PhD

Deputy Director of Strategic Initiatives, Comprehensive Cancer Center

Director, Division of Brain Tumor Research

Developmental Neurobiology

Shari M. Capers, MBA, MHA

Senior Vice President

Strategic Planning & Decision Support

Catherine I. Corbin, AIA

Senior Vice President

Chief Business Innovation Officer

John D. Crispino, PhD, MBA

Director, Division of Experimental Hematology Hematology

Sarah Currie, RNC, MSN, NEA-BC

Senior Vice President

Chief Nursing Executive

Andrew M. Davidoff, MD Chair, Surgery

Robyn Diaz, JD

Executive Vice President

Chief Legal Officer

Michael A. Dyer, PhD

Chair, Developmental Neurobiology

David W. Ellison, MD, PhD Chair, Pathology

Sarah M. Federico, MD

Director, Division of Solid Tumor Oncology

Richard S. Finkel, MD

Director, Center for Experimental Neurotherapeutics

Pediatric Medicine

Elizabeth Fox, MD, MS

Senior Vice President, Clinical Trials Research Oncology

Amar J. Gajjar, MD Chair, Pediatric Medicine

Terrence L. Geiger, MD, PhD

Senior Vice President

Deputy Director for Academic & Biomedical Operations

Interim Chair, Immunology Pathology

Stephen M. Gottschalk, MD Chair, Bone Marrow Transplantation & Cellular Therapy

Douglas R. Green, PhD Immunology

James M. Hoffman, PharmD

Senior Vice President, Quality and Safety

Chief Patient Safety Office

Pharmacy & Pharmaceutical Sciences

Melissa M. Hudson, MD

Director, Division of Cancer Survivorship

Oncology, Epidemiology & Cancer Control, Psychology & Biobehavioral Sciences

Charalampos G. Kalodimos, PhD

Chair, Structural Biology

Pat Keel, MHA

Executive Vice President

Chief Administrative & Financial Officer

Richard W. Kriwacki, PhD

Structural Biology

Kevin R. Krull, PhD Chair, Psychology & Biobehavioral Sciences

Mary E. (Beth) McCarville, MD1

Interim Chair, Diagnostic Imaging5

Chief, Clinical Radiation

Chief, Body Imaging Section

Jonathan A. McCullers, MD

Chair, Pediatrics, University of Tennessee Health Science Center

Pediatrician-in-Chief, Le Bonheur Children’s Hospital

Peter J. McKinnon, PhD

Director, Center for Neurological Disease Research

Vice Chair, Cell & Molecular Biology

Thomas E. Merchant, DO, PhD Chair, Radiation Oncology

Shondra Miller, PhD

Vice President, Cancer Center Shared Resources Cell & Molecular Biology

Motomi Mori, PhD, MBA Chair, Biostatistics

Charles G. Mullighan, MBBS(Hons), MSc, MD

Senior Deputy Director of Strategic Initiatives, Comprehensive Cancer Center Director, Center of Excellence for Leukemia Services

Pathology

Kirsten K. Ness, PT, PhD, FAPTA

Epidemiology & Cancer Control

Ellis J. Neufeld, MD, PhD

Executive Vice President

Clinical Director

Physician-in-Chief

Alberto S. Pappo, MD Oncology

Julie R. Park, MD

Chair, Oncology

Keith Perry, MBA

Senior Vice President

Chief Information Officer

Ching-Hon Pui, MD

Oncology

Octavio Ramilo, MD

Chair, Infectious Diseases

Charles W.M. Roberts, MD, PhD

Executive Vice President

Director, Comprehensive Cancer Center

Lori Spicer Robertson

Vice President

Carlos Rodriguez-Galindo, MD

Executive Vice President

Chair, Global Pediatric Medicine

Director, St. Jude Global

P. David Rogers, PharmD, PhD

Chair, Pharmacy & Pharmaceutical Sciences

Martine F. Roussel, PhD

Tumor Cell Biology

Charles J. Sherr, MD, PhD Chair, Tumor Cell Biology

Andrew D. Smith, MD, PhD

Chair, Diagnostic Imaging5

J. Paul Taylor, MD, PhD

Executive Vice President

Scientific Director

Chair, Cell & Molecular Biology

Director, Pediatric Translational Neuroscience Initiative

Victor J. Torres, PhD

Chair, Host–Microbe Interactions

Steven M. Varga, PhD

Chair and Dean, St. Jude Graduate School of Biomedical Sciences

Infectious Diseases

Mitchell J. Weiss, MD, PhD

Chair, Hematology

Jiyang Yu, PhD

Interim Chair, Computational Biology

2024 Scientific Advisory Board

This panel of physicians and scientists, serving during 2024, fostered the institution’s development through discussion with faculty members, reports to the Board of Governors, and advice to the President and CEO on scientific and clinical research directions.

John Maris, MD, Chair

Giulio D’Angio Chair in Neuroblastoma Research

Perelman School of Medicine at the University of Pennsylvania

Division of Oncology

Children’s Hospital of Philadelphia

Smita Bhatia, MD, MPH, Vice Chair

Gay and Bew White Endowed Chair in Pediatric Oncology

Distinguished Professor, Pediatric Oncology

Vice Chair for Outcomes Research, Department of Pediatrics

Director, Institute for Cancer Outcomes and Survivorship

University of Alabama at Birmingham School of Medicine

University of Alabama at Birmingham

Kevin Shannon, MD, Vice Chair

American Cancer Society

Research Professor

Roma and Marvin Auerback

Distinguished Professorship in Pediatric Molecular Oncology

University of California

– San Francisco

Helen Diller Family

Comprehensive Cancer Center

Susan Ackerman, PhD

HHMI Investigator

Stephen W. Kuffler Chair in Biology

Distinguished Professor, Departments of Neurobiology and Cellular and Molecular Medicine

University of California – San Diego

National Academy of Medicine

National Academy of Sciences

Scott Armstrong, MD, PhD

President, Dana-Farber/ Boston Children’s Cancer and Blood Disorders Center

Chair, Department of Pediatric Oncology

Associate Chief, Division of Hematology/Oncology, Boston Children’s Hospital

David G. Nathan Professor of Pediatrics, Harvard Medical School

Chief Research Strategy Officer

Senior Vice President for Drug Discovery

Dana-Farber Cancer Institute

National Academy of Medicine

Carsten Bönnemann, MD

Senior Investigator and Chief, Neuromuscular & Neurogenetic Diseases of Childhood

Acting Chief, Neurogenetics Branch

National Institute of Neurological Disorders and Stroke, National Institutes of Health

Adjunct Professor of Neurology, University of Pennsylvania Perelman School of Medicine

Michael Eck, MD, PhD

Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

Professor of Cancer Biology, Dana-Farber Cancer Institute

David Ginsburg, MD

James V. Neel Distinguished University Professor

Departments of Internal Medicine, Human Genetics, and Pediatrics University of Michigan Medical School

National Academy of Medicine

National Academy of Sciences

Nathanael Gray, PhD

Member, ChEM-H

Program Leader, Small Molecule Drug Discovery for the Innovative Medicines Accelerator

Co-Director, Cancer Drug Discovery

Co-Leader, Cancer Therapeutics Research Program

Krishnan-Shah Family Professor, Chemical and Systems Biology

Stanford University

Katherine High, MD

Emeritus Professor of Pediatrics, University of Pennsylvania Perelman School of Medicine

Visiting Professor, The Rockefeller University

National Academy of Medicine

National Academy of Sciences

Patrick Loehrer, MD

HH Gregg Professor of Oncology

Distinguished Professor

Indiana University School of Medicine

Sallie Permar, MD, PhD

Pediatrician-in-Chief, New York-Presbyterian/Weill Cornell Medical Center

Nancy C. Paduano

Professor and Chair

Professor of Immunology and Microbial Pathogenesis

Weill Cornell Medicine

Rob Pieters, MD, PhD, MSc

Board of Directors, Chief Medical Officer

Princess Maxima Center for Pediatric Oncology

Stanley Riddell, MD

Burke O’Reilly Family Endowed Chair in Immunotherapy

Professor, Department of Medicine

Fred Hutchinson Cancer Research Center

Kimberly Stegmaier, MD

Ted Williams Investigator, Dana-Farber Cancer Institute

Vice Chair of Pediatric Oncology

Research, Dana-Farber Institute

Co-Director, Pediatric Hematologic Malignancy Program, Boston

Children’s Hospital and DanaFarber Cancer Institute

Professor of Pediatrics, Harvard Medical School

Member, Broad Institute

Viviane Tabar, MD

Theresa C. Feng Professor in Neurosurgical Oncology

Chair, Department of Neurosurgery

Memorial Sloan Kettering Cancer Center

National Academy of Medicine

Sarah Teichmann, FMedSci FRS Professor

Wellcome – MRC Cambridge

Stem Cell Institute

Department of Medicine

University of Cambridge

1 Data represent the number of beds in use. St. Jude is licensed for 80 beds

2 Data include original data articles

3 Data include 59 full-time St. Jude fellows and 114 rotating fellows and residents from the University of Tennessee Health Science Center or other medical schools

4 Data represent the period July 1, 2022 to June 30, 2024

5 Average number of employees in 2024

Translating Science into Survival Scientific Report 2025

Editorial Direction

Erin Podolak, MA

Jennifer L. Stripay, PhD

Creative Direction

Madison Newton-Rice, MS

Photography

Justin Veneman

Terrence L. Geiger, MD, PhD

Greg Armstrong, MD

M. Madan Babu, PhD, FRS

Scott Blanchard, PhD

Tara Brinkman, PhD

Hongbo Chi, PhD

Stephanie Dixon, MD

Matthew Ehrhardt, MD

Yong Feng, PhD

Aditya Gaur, MD

I-Chan Huang, PhD

Contributing Writers

Josh Dodson, PhD

LaToyia Downs, PhD

Matthew Gaschk

Alex Generous, PhD

Kathryn McCullough, MA

Brian O’Flynn, PhD

Jessica Rubino, PhD

Taylor Wewel

Lead Designer

Leena Xaypanya

Contributing Designers

Briana Williams

Rachel Byrd

Editing Support

Angela J. McArthur, PhD, ELS

Faculty Feature Editors

Hiroto Inaba, MD, PhD

Jeffery Klco, MD, PhD

Xiaotu Ma, PhD

Stephen Mack, PhD

Charles, Mullighan, MBBS (Hons), MSc, MD

Kim Nichols, MD

Stacey Ogden, PhD

Ching-Hon Pui, MD

Charles Roberts, MD, PhD

Yadav Sapkota, PhD

Daniel Savic, PhD

Lindsay Schwarz, PhD

Akshay Sharma, MBBS

Andrew Smith, MD, PhD

Brandon Triplett, MD

Lu Wang, MD, PhD

Jun J. Yang, PhD

Benjamin Youngblood, PhD

Jiyang Yu, PhD

Caitlin Zebley, MD, PhD