The Strategic Communication, Education and Outreach team curates stories for press release using scientific impact and institutional strategic alignment as central criteria. The stories featured represent an esteemed fraction of discovery and accomplishment across the St. Jude research and clinical enterprise. Additional media engagement is pursued for each release, accompanied by promotion across our channels and platforms.
Work published by St. Jude investigators in Q4FY24 was representative of the breadth and depth of our fundamental and translational research enterprise. From observations on structure-function relationships in proteins, to advancements in imaging techniques, demonstration of computational innovation, to informed predictions on survivorship, St. Jude research advanced the fields of immunology and infectious disease, cancer genetics, and preclinical therapeutics. Additionally, St. Jude celebrated prestigious accomplishments of several faculty, and welcome the newest department chair to the institution.
CANCER CELL
Targeting vulnerability in B-cell development leads to novel drug combination for leukemia
• B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with a poor survival rate for relapsed or resistant disease.
• Using single-cell pharmacology, St. Jude scientists uncovered why some B-ALL cells are resistant to chemotherapy based on their developmental stage.
• Findings show that combining asparaginase (a chemotherapy) with a targeted drug, venetoclax, better controlled multiple high-risk B-ALL subtypes in preclinical models.
• This drug combination has a high probability of being tested in the next generation of B-ALL clinical trials, and the research approach may be adapted to other cancers.
Learn more: Targeting vulnerability in B-cell development leads to novel drug combination for leukemia
CANCER DISCOVERY
St. Jude survivorship portal brings researchers ‘one-click’ away from discovery
• The St. Jude survivorship portal, part of the St. Jude Cloud ecosystem, is the first data portal for sharing, analyzing and visualizing comprehensive pediatric cancer survivorship data.
• The portal houses multiple dimensions of data from over 7,700 childhood cancer survivors from the Childhood Cancer Survivor Study (CCSS) and St. Jude Lifetime Cohort.
• The portal is free and open access, has already enabled various discoveries and provides curated data paired with visualization and on-the-fly data analysis.
Learn more: St. Jude survivorship portal brings researchers ‘one-click’ away from discovery
NATURE
New drug prevents flu-related inflammation and lung damage
• Influenza virus infections can cause life-threatening lung damage in some patients, and advanced forms of these infections have no effective therapeutics.
• St. Jude scientists showed that a newly created drug can prevent the runaway inflammation that causes lung injury, while still allowing the immune system to tackle the virus.
• The drug is a first-of-its-kind inhibitor and provides promise for treating patients with advanced infections.
Learn more: New drug prevents flu-related inflammation and lung damage
NATURE MICROBIOLOGY
Metabolic health before vaccination determines effectiveness of anti-flu response
• On average, the annual influenza (flu) vaccine has become less effective over time. This is due in part to the rising number of people with high body mass index (BMI) and a pattern of reduced vaccine efficacy in people with obesity.
• St. Jude researchers found that introduction of a healthy diet prior to influenza vaccination protected from later flu infection in preclinical models.
• The findings suggest that ‘anti-flu’ response is fixed by metabolic health at the time of vaccination and that improving metabolic health, especially in vulnerable populations, may improve vaccine efficacy.
Learn more: Metabolic health before vaccination determines effectiveness of anti-flu response
JOURNAL OF CLINICAL ONCOLOGY
Genetics predict type 2 diabetes risk and disparities in childhood cancer survivors
• Childhood cancer survivors experience increased risk for cardiovascular disease and greater prevalence of cardiovascular risk factors such as type 2 diabetes.
• A report from the St. Jude Lifetime cohort study (St. Jude LIFE) found four genetic changes associated with this increased risk for type 2 diabetes. These variants occurred with higher frequency in survivors of African descent.
• The work furthers our understanding of the mechanisms underlying diabetes among survivors of childhood cancer and may facilitate future studies designed to identify survivors who may benefit from proactive monitoring and early intervention.
Learn more: Genetics predict type 2 diabetes risk and disparities in childhood cancer survivors
NATURE COMMUNICATIONS
Targeting specific protein regions offers a new treatment approach in medulloblastoma
• There are four molecular subgroups of medulloblastoma, the most common malignant childhood brain tumor. Of those, Group 3 has the worst outcomes.
• Scientists at St. Jude discovered that inhibiting a specific domain in a key protein was effective in high-risk Group 3 medulloblastoma.
• The researchers modified an existing small-molecule inhibitor of this domain, inobrodib, improving its ability to cross the blood brain barrier and reach the tumor.
• Results suggest this novel version of inobrodib should be pursued for preclinical and potentially clinical evaluation.
Learn more: Targeting specific protein regions offers a new treatment approach in medulloblastoma
NATURE COMMUNICATIONS
Unraveling the roles of non-coding DNA explains childhood cancer’s resistance to chemotherapy
• Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Despite high cure rates, patients with relapsed or recurrent disease experience poor survival rates due to the development of chemotherapy resistance.
• St. Jude researchers screened the genomes of chemotherapy resistant ALL samples for specific changes in non-coding regions of DNA. Based on the top screening results, they deciphered the mechanism of action to define novel mechanisms of chemotherapy resistance.
• By combining state-of-the-art genomic technologies, scientists developed an approach that could be adapted to better understand traits affected by changes in the non-coding DNA.
Learn more: Unraveling the roles of non-coding DNA explains childhood cancer’s resistance to chemotherapy
NATURE COMMUNICATIONS
Pan-cancer analysis uncovers a new class of promising CAR T-cell immunotherapy targets
• Immunotherapy using modified chimeric antigen receptor (CAR) T cells has greatly improved survival rates for some relapsed and recurrent pediatric leukemias. However, these approaches have not been as effective in treating solid or brain tumors.
• Scientists at St. Jude identified a set of 156 potential targets for CAR T cells in solid and brain tumors. These targets all belong to a novel class, cancer-specific exons (CSE). They validated targets in relevant cell lines and showed that CAR T cells designed to target these candidates significantly increased survival in preclinical models.
• The list of candidates is publicly available, enabling researchers worldwide to explore potential CAR T-cell therapies for solid and brain tumors.
Learn more: Pan-cancer analysis uncovers a new class of promising CAR T-cell immunotherapy targets
NATURE COMMUNICATIONS
Novel inhibitor insights offer pathway to preventing PXR-associated drug resistance
• Pregnane X receptor (PXR) activates the expression of genes that metabolizes drugs including chemotherapy, antivirals and other pharmaceuticals, reducing treatment efficacy.
• Blocking the activity of PXR has been notoriously difficult. Researchers at St. Jude leveraged chemical and structural studies to better understand the dynamics of PXR function.
• They demonstrated how molecules could be modified to switch between activating and inhibiting PXR, facilitating future design of more effective PXR inhibitors. These inhibitors could be administered alongside chemotherapy or other treatments to reduce PXR-mediated drug metabolism.
Learn more: Novel inhibitor insights offer pathway to preventing PXR-associated drug resistance
MOLECULAR CELL
Repurposed protease controls important signaling molecule-activating protein
• The protein ADAM17 is vital in the release of over 80 signaling molecules, including tumor necrosis factor (TNF), which functions as the first distress signal in an immune response.
• Directly targeting ADAM17 often affects other critical ADAM family members. Structural biology studies from St. Jude discovered the mechanism by which a ‘pseudoprotease’ controls the maturation of ADAM17, specifically.
• Future drug design could focus on targeting the interaction between ADAM17 and its protease, to mitigate aberrant TNF activation.
Learn more: Repurposed protease controls important signaling molecule-activating protein
NATURE NEUROSCIENCE
Cell-targeting technology allows researchers to isolate neuronal subpopulations and link them to behavioral states
• It is increasingly important to understand the role that diverse cell types play within the brain and body.
• St. Jude scientists developed a new tool to access and precisely manipulate groups of cells based on specific features. It combines the power of adeno-associated virus (AAV)-based reporter tools with ribozyme technology to control gene expression with exquisite precision.
• Researchers used this tool to identify a subset of norepinephrine neurons that have not previously been identified or characterized.
Learn more: Cell-targeting technology allows researchers to isolate neuronal subpopulations and link them to behavioral states
NATURE IMMUNOLOGY
‘Goldilocks’ binding strength determines anti-cancer T-cell efficacy and fate
• Immunotherapy approaches that enhance a patient’s natural anti-cancer immune cell response have been successful in treating refractory leukemias but have had little success in controlling solid tumors.
• This limited success is due to the ‘exhaustion’ of potential cancer-killing T cells. Findings from St. Jude showed that how tight a parental T cell binds to cancer proteins determines whether offspring will become functional anti-cancer cells or dysfunctional ‘exhausted’ T cells.
• When T cells interact with a cancer-targeting protein, a ‘Goldilocks’ scenario was observed – binding strength between the T cell and its target must be ‘just-right’ to generate and maintain anti-cancer effects. This work has broad implications for immunotherapy development.
Learn more: ‘Goldilocks’ binding strength determines anti-cancer T-cell efficacy and fate
NATURE AGING
Age is just a number: Immune cell ‘epigenetic clock’ ticks independently of organism lifespan
• Over time, as we age, our cell function declines, but T cells have demonstrated a unique ability to proliferate endlessly.
• A collaborative effort between St. Jude and the University of Minnesota deciphered methylation patterns in DNA to create a “T cell epigenetic clock”. They found that T cells can survive at least four times longer than their organism of origin.
• These findings advance our understanding of T-cell epigenetic aging, allowing for the consideration of potential therapies which halt, or even reverse, age-related impairments.
Learn more: Age is just a number: Immune cell ‘epigenetic clock’ ticks independently of organism lifespan
NATURE METHODS
Novel insights into fluorescent ‘dark states’ illuminate ways forward for improved imaging
• Single-molecule fluorescence resonance energy transfer (smFRET) is a technique that allows researchers to measure protein dynamics. The process relies on using lasers to excite and relax electrons called fluorophores.
• Scientists at St. Jude found that the efficacy of smFRET varies as a function of a laser’s intensity. This variation is due largely to electrons getting caught in what’s called a “triplet state”.
• Pioneers in the design of fluorophores, the researchers created fluorophores that can resist this triplet state, ensuring that the true dynamics within biomolecules can be faithfully examined.
Learn more: Novel insights into fluorescent ‘dark states’ illuminate ways forward for improved imaging
CELL
St. Jude scientists solve decades long mystery of NLRC5 sensor function in cell death and disease
• The innate immune system protects the body from both external threats and internal threats. The system relies on innate immune sensors to detect and transmit signals.
• Work from St. Jude identified the triggers for a specific immune sensor, solving a decades long mystery. Researchers found that a particular protein, NLRC5, acts as both a sensor and a cell death trigger.
• NLRC5 is associated with cancers, infectious diseases and inflammatory disorders. By deleting NLRC5, scientists were able to protect against disease pathology in hemolytic and inflammatory models.
Learn more: St. Jude scientists solve decades long mystery of NLRC5 sensor function in cell death and disease
JAMA ONCOLOGY
Children genetically prone to cancer benefit from early standardized surveillance
• For patients and their siblings with underlying predisposition to cancer, surveillance for new tumors is often recommended, but it is unclear when that surveillance should begin.
• St. Jude scientists showed that beginning surveillance soon after diagnosing a predisposition syndrome led to the discovery of early-stage asymptomatic tumors, many of which could be completely removed by surgery. Some of these were even detected while patients were undergoing therapy for an existing tumor.
• The work provided evidence that current screening methods show excellent performance and should encourage providers to regularly and proactively surveil patients with cancer-predisposing syndromes.
Learn more: Children genetically prone to cancer benefit from early standardized surveillance
Renowned St. Jude clinician and researcher to receive coveted award at AACR annual meeting
Each year, members of the cancer research community including scientists, clinicians, and healthcare professionals, cancer survivors, patients and advocates attend the American Association for Cancer Research (AACR) annual meeting. AACR honored Ching-Hon Pui, MD at this year’s meeting with the St. Baldrick’s Foundation Award for Outstanding Achievement in Pediatric Cancer Research.
Andrew Smith, MD, PhD, named chair of Diagnostic Imaging at St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital announced Andrew Smith, MD, PhD, as the new chair of the Diagnostic Imaging Department. He is a nationally recognized academic radiologist with expertise in body and oncologic imaging, clinical trials and imaging research and the application of artificial intelligence (AI) in imaging and medicine.
Hongbo Chi, PhD names 2023 AAAS Fellow
Hongbo Chi, PhD, a faculty member and the Robert G. Webster Endowed Chair in Immunology at St. Jude Children’s Research Hospital, has been recognized as a fellow of the American Association for the Advancement of Science (AAAS), the world’s largest general scientific society and publisher of the Science Family of Journals. Chi will be formally inducted September 21, during the organization’s annual Fellows Forum in Washington D.C.
In festivities across campus, the St. Jude Cell Therapy Program celebrated the production of its 100th batch of cell therapy product. St. Jude faculty and staff watched as it was transported from the Children’s GMP to the Human Applications Lab, where it will be stored before patient use.
As part of Brain Tumor Awareness Month, we highlight investigators such as Kelsey Bertrand, MD, a pediatric neuro-oncologist whose work focuses on developing treatment of ependymoma, the third most common malignant pediatric brain tumor.
As we envision the future of gene editing, St. Jude is committed to investing in top-tier technologies to better understand the
inhibitor, PD901 (mirdametinib), that demonstrates potential for crossing the blood brain barrier and inhibiting a protein signal that drives pLGG tumors.
To celebrate Nursing Appreciation Week, we asked our St. Jude staff what the nursing team means to them and how they impact our patients’ quality of care. The consensus? Our nurses are the heart of the institution. From advancing clinical care to working side-by-side with clinical scientists and improving patient outcomes at the bedside, our nurses are committed to providing exceptional care.
Looking back at her teenaged self when she had been recently diagnosed with acute lymphoblastic leukemia (ALL), Emily Browne she says she was the direct beneficiary of the advances St. Jude has made in methotrexate pharmacodynamics and the pursuit to replace cranial radiation with intrathecal therapy. Now two decades into her career at St. Jude and nearly 29 years since her diagnosis, Browne shares her story in honor of National Cancer Survivors Day.
Q4FY24: EARNED MEDIA
A genetic analysis sheds light on when the outbreak began, how the virus spread and where it may be going.
Muscle from a sick dairy cow tested positive for the virus. The meat did not enter the commercial food supply, which officials said remained safe.
Safe to Drink
Dr. Richard Webby
Should you be concerned about bird flu in your milk?
National Geographic spoke to a member of the World Health Organization about bird flu infections in cattle and its threats to the food supply.
Boys Need the HPV Cancer Vaccine as Much as Girls
Muscle from a sick dairy cow tested positive for the virus. The meat did not enter the commercial food supply, which officials said remained safe.
Pfizer’s First Gene Therapy Gets Approval for Clotting Disorder
Pfizer Inc. won US approval for its first gene therapy, expanding into a promising field of medicine that has proved to be a challenging business.
