Q3FY25 Quarterly Report by sjcrh

SHARING OUR STORIES

From January to March of this year (Q3FY25), St. Jude investigators published work that advanced our understanding and treatment of neuroblastoma, childhood leukemia, and spinal muscular atrophy. Researchers also made significant strides in the development of computational tools and the harnessing of imaging technologies and spatial transcriptomics to better understand disease biology.

The launch of our Global Platform for Access to Childhood Cancer Medicines was celebrated across the world, setting the stage for transformative international collaboration. Media outlets also highlighted St. Jude’s expertise in infectious diseases, including extensive commentary from Dr. Richard Webby on bird flu. Additionally, our faculty has received well-deserved recognition through several prestigious awards, underscoring their exceptional contributions and thought leadership.

ST. JUDE AND NATURE PARTNER TO PROFILE PROGRESS

SCEO is promoting St. Jude pioneering expertise and elevating institutional reputation by sharing stories of research, discovery and impact through featured content on Nature platforms. We work directly with Nature Research Custom Media to develop high-quality content that adheres to the Nature editorial standards. These articles create visibility and awareness around the research enterprise, initiatives and those representing the organization.

In Q3FY25, we highlighted publications in global pediatric research and showcased Dr. Downing’s vision for St. Jude as a global catalyst in accelerating discovery and impact. Read more in the Beyond borders: global paediatric medicine section of our new collections page on nature.com

Learn more: Beyond borders: global paediatric medicine

SELECT SCIENTIFIC DISCOVERIES

Mitochondrial DNA plays an underappreciated role in leukemia development

Mondira Kundu, MD, PhD

Science Advances

• Mitochondrial DNA (mtDNA) plays a critical role in cancer growth, with varying levels of mutations influencing leukemogenesis differently.

• Moderate mtDNA mutations amplify leukemia growth by enabling metabolic reprogramming, while high mutation levels shut down mitochondria, blocking tumor progression.

• Blocking the kinase “off switch” of pyruvate dehydrogenase restores metabolic plasticity in cells with high mtDNA mutation burdens, promoting leukemogenesis.

• This research reveals a significant connection between mtDNA mutation levels and cancer growth, offering new insights into potential therapeutic strategies.

Discovery of ‘pliancy genes’ showcases role of latent epigenetic programs in retinal recovery

Michael Dyer, PhD

Developmental Cell

• St. Jude scientists used single-cell sequencing to study the behavior, interactions, and responses of distinct retinal cell types, including Müller glia.

• Single-cell RNA-seq and ATAC-seq revealed that Müller glia have open chromatin architecture, allowing gene accessibility without active expression.

• Under stress conditions mimicking disease, pliancy genes in the open chromatin are activated, triggering rapid cytokine signaling and inflammatory immune responses.

• This research provides critical insights into the mechanisms of inflammation in retinal diseases, offering potential pathways for therapeutic development.

Learn more: Visit the St. Jude Newsroom to read the full press release.

Signaling circuit interplay pushes newborn neurons out of the neuronal nest

David Solecki, PhD

Nature Communications

• Researchers at St. Jude identified the molecular mechanisms driving neuronal migration from the germinal zone, a critical process for cerebellum formation.

• The guidance molecule Netrin-1 “pushes” developed neurons out of the germinal zone, while the ubiquitin ligase Siah2 “pulls” undeveloped neurons back by degrading key proteins.

• A protein complex involving Dcc, Pard3, and JamC links adhesion and guidance signaling to coordinate neuron migration.

• Understanding these mechanisms provides crucial insights into brain development and the formation of functional neural circuits.

St. Jude scientists create scalable solution for analyzing single-cell

data

Paul Geeleher, PhD

Cell Genomics

• Single-cell gene expression data provides detailed insights into diseases, but its vast scale creates challenges for effective analysis using current computational tools.

• Existing methods rely on assumptions that introduce bias and produce inconsistent results, limiting their reliability.

• St. Jude developed CSI-GEP, an advanced computational toolkit leveraging unsupervised machine learning and GPUs to analyze large single-cell datasets without bias.

• This innovation enables scientists across disciplines to extract more accurate and robust insights from complex single-cell data, advancing research capabilities.

Learn more: Visit the St. Jude Newsroom to read the full press release.

ZIC1 gene drives distinct medulloblastoma types in different ways

Paul Northcott, PhD

Nature Genetics

• Medulloblastoma, the most common malignant pediatric brain tumor, has distinct subtypes with different genetic drivers, complicating treatment strategies.

• St. Jude researchers analyzed the role of ZIC1 mutations in medulloblastoma, comparing their effects in Group 4 (G4) and Sonic Hedgehog (SHH) subtypes.

• ZIC1 mutations drive medulloblastoma through different mechanisms — loss of function in G4 tumors and gain of function in SHH tumors — indicating subtype-specific disease pathways.

• These findings highlight the need for tailored therapies, paving the way for precision treatments that target unique genetic drivers.

St. Jude researchers create tool incorporating transcriptome size to improve RNA-seq analysis

Jiyang Yu, PhD

Nature Communications

• Gene expression, the process of creating RNA and proteins from DNA, is central to biological research across fields like cancer, neuroscience, and virology.

• Existing computational tools for gene expression analysis rely on flawed assumptions, such as uniform RNA expression across cells, leading to inaccuracies.

• St. Jude researchers developed ReDeconv, a computational tool that accounts for transcriptome size, reducing errors in single-cell and bulk RNA-seq analyses.

• ReDeconv enhances the accuracy of gene expression studies, enabling scientists to extract more meaningful biological insights from RNA-sequencing data.

Learn more: Visit the St. Jude Newsroom to read the full press release.

Promising results from first prenatal therapy for spinal muscular atrophy

Richard Finkel, MD

New England Journal of Medicine

• St. Jude scientists led the first in-utero treatment of spinal muscular atrophy (SMA) using risdiplam, an orally administered drug typically given after birth.

• SMA, caused by a lack of survival motor neuron protein, affects approximately 1 in 11,000 births in the U.S. and, if untreated, leads to progressive muscle weakness and death.

• A single-patient FDA–approved investigational study treated a fetus genetically predicted to develop SMA-1, resulting in the child showing no signs of SMA over two years after birth.

• This study demonstrates the safety and feasibility of prenatal SMA treatment and supports further research into prenatal approaches for managing the disorder.

Altering tumor microenvironment may reduce relapses after leukemia immunotherapy

Terrence Geiger, MD, PhD; Jiyang Yu, PhD

Cancer Discovery

• Immunotherapy, including CAR T cells, has shown success in treating B-cell acute lymphoblastic leukemia (B-ALL), but relapse and resistance remain significant challenges.

• St. Jude researchers identified diminished GPR65 gene activity in tumors resistant to immunotherapy, which promotes an immunosuppressive microenvironment by recruiting macrophages.

• Reduced GPR65 gene activity increases VEGFA expression, attracting macrophages that impair CAR T–cell effectiveness, but combining CAR T cells with a VEGF inhibitor improved outcomes in preclinical models.

• These findings suggest GPR65 as a potential biomarker for immunotherapy success and support further evaluation of combination therapies to enhance treatment efficacy.

Learn more: Visit the St. Jude Newsroom to read the full press release.

St. Jude scientists solve the mystery of how the drug retinoic acid works to treat

neuroblastoma

Paul Geeleher, PhD

Nature Communications

• Neuroblastoma is a pediatric solid tumor with a poor prognosis in high-risk cases, though retinoic acid improves survival by targeting metastasized disease, not the primary tumor.

• Researchers found that retinoic acid’s antineuroblastoma activity depends on the cellular microenvironment, particularly the bone marrow, where the bone morphogenic protein (BMP) signaling is active.

• Retinoic acid and BMP signaling interact to trigger cell death in metastasized neuroblastoma by hijacking a normal developmental process.

• This study uncovers a novel therapeutic mechanism and opens the door to exploring combination therapies that exploit normal developmental pathways preserved in cancer.

Repurposed ALS drug becomes imaging probe to help diagnose neurodegeneration

Kiel Neumann, PhD

Nature Biomedical Engineering

• Researchers at St. Jude are repurposing the antioxidant drug edaravone to enhance the use of positron emission tomography (PET) in detecting neurological diseases.

• Radiolabeled edaravone allows visualization and quantification of reactive oxygen and nitrogen species (RONS), which are linked to oxidative stress and brain injury in conditions like ALS and stroke.

• This technique combines diagnosis and treatment by targeting oxidative stress in the central nervous system, offering a novel approach to neurodegenerative disease detection.

• The technology leverages an FDA–approved therapy, providing a clear path to clinical application with significant potential for improving neurological disease management.

Learn more: Visit the St. Jude Newsroom to read the full press release.

Spotiphy integrative analysis tool turns spatial RNA sequencing into imager

Jiyang Yu, PhD

Nature Methods

• Spatial transcriptomics identifies where genes are expressed, in which cells, and in what quantities, enabling deeper insights into disease biology.

• Current methods face limitations, requiring a trade-off between high image resolution and broad gene detection.

• St. Jude scientists developed Spotiphy, a generative AI-powered tool that achieves true single-cell resolution and high genome coverage by bridging imaging and sequencing data gaps.

• Spotiphy, validated in neurological disease and cancer, is freely available to researchers, offering a powerful resource for advancing spatial transcriptomics and uncovering new biology.

Current antivirals less effective against severe infection caused by bird flu in cows’ milk

Richard Webby, PhD

Nature Microbiology

• The H5N1 avian influenza virus has been detected in cows’ milk, with human infections reported among individuals exposed on dairy farms.

• St. Jude researchers tested the effectiveness of FDA–approved antivirals baloxavir and oseltamivir in a preclinical model exposed to infected milk via different routes.

• Both antivirals showed variable effectiveness, but oral exposure to raw infected milk caused severe, systemic infections that neither antiviral could mitigate.

• This study highlights the limited effectiveness of current antivirals against this H5N1 strain and underscores the importance of preventative measures, such as avoiding raw milk consumption and protecting dairy workers.

Learn more: Visit the St. Jude Newsroom to read the full press release.

ANNOUNCEMENTS

Elizabeth Hillman joins St. Jude as chair of Imaging Sciences

St. Jude Children’s Research Hospital announced that Elizabeth M.C. Hillman, PhD, has been selected as the founding chair of its new Department of Imaging Sciences. Hillman is a pioneer in imaging method development, with a track record of developing high-speed microscopes and invivo imaging systems to study living tissues. The department will establish a new community of technology innovators at St. Jude, whose tools and techniques will accelerate scientific discovery and improve the understanding and diagnosis of catastrophic childhood diseases.

Damon Runyon Cancer Research Foundation and St. Jude Children’s Research Hospital invest $1.8M in childhood cancer research

The Damon Runyon Cancer Research Foundation and St. Jude Children’s Research Hospital have announced their newest class of pediatric cancer research fellows, each of whom will receive funding for four years to support an innovative research project with the potential to significantly impact the diagnosis or treatment of one or more pediatric cancers. Launched in 2024, the Damon Runyon–St. Jude Pediatric Cancer Research Fellowship aims to address a funding gap that drives top talent to seek more prevalent opportunities in adult cancer research or the pharmaceutical sector. Fellows are selected by a distinguished committee of leaders in the field.

SELECT FACULTY AWARDS

Lindsay Schwarz of St. Jude Children’s Research Hospital receives presidential science award

Lindsay Schwarz, PhD, an assistant member of the Department of Developmental Neurobiology at St. Jude Children’s Research Hospital, is a recipient of the Presidential Early Career Award for Scientists and Engineers (PECASE) — the highest honor bestowed by the U.S. government to outstanding scientists and engineers who are beginning their independent research. The award recognizes innovative and far-reaching developments in science and technology and enhances connections between research and societal impacts.

Learn more: Visit the St. Jude Newsroom to read the full press release.

Scott Blanchard recognized with the Kazuhiko Kinosita Award in

Single-Molecule Biophysics

This award is intended to encourage investigators to promote further developments in single-molecule biophysics, to advance the type of cross-disciplinary research that is characteristic of this field, and to elevate an appreciation of single-molecule studies among scientists.

Read more about Blanchard’s work in singlemolecule imaging.

The American Society for Clinical Investigation Elects Jeff Klco as a 2025 Member

Membership to the ASCI honors physicians who have “accomplished meritorious original, creative, and independent investigations in the clinical or allied sciences of medicine” and who enjoy “unimpeachable moral standing in the medical profession.”

Tanja Mittag, PhD, announced as a 2025 Fellow of the Biophysical Society

This award honors the Society’s distinguished members who have demonstrated excellence in science and contributed to the expansion of the field of biophysics.

Read more about how Mittag bridges physics and biology.

Hudson receives the 2025 ASCO Pediatric Oncology Award

Melissa Hudson is recognized for her leadership in further developing and disseminating the St. Jude model of risk-based survivor care, known as the After Completion of Therapy (ACT) Clinic.

Caitlin Zebley selected to receive a 2025 Young Physician-Scientist Award from the ASCI

The ASCI (American Society for Clinical Investigation) Young Physician-Scientist Awards recognize physician-scientists who are early in their first faculty appointment and have made notable achievements in their research.

Melissa

EARNED MEDIA

First-Ever Prenatal Treatment for Spinal Muscular

Atrophy Shows Promise

The first prenatal treatment for spinal muscular atrophy showed promise in a single case report. More than two years after the child was born, no identifiable features of SMA have been observed. The child was treated in utero with risdiplam and continues to receive the drug daily.

“The overarching goal in this first case study was to demonstrate feasibility of prenatal therapy with one of these drugs, generate safety data, and gather biomarker and clinical data that might give a hint of improved efficacy when compared to initiation of treatment postnatally,” said Richard Finkel, MD.

A Miracle Maker in Pediatric Hematologic Cancers

A love of collaborating with colleagues from around the globe and a fiery passion to help children diagnosed with cancer led Ching-Hon Pui, MD, to dramatically improve outcomes in pediatric oncology.

The thorough profile of the trailblazing researcher details his mentors, inspiration and motivation to continue his work after more than 40 years at St. Jude. “No one has done more for children with leukemia around the world than Dr. Pui,” said James R. Downing, MD, president and CEO.

His entire life’s passion, is without question predicated on his relationship with his patients. “I admire the resilience of my patients. No matter how sick they are, they amaze me with their ability to bounce back—a trait that has taught me to be stubborn and slow to give up,” Pui said.

Why Some Doctors Over-Trust AI and Don’t Even Realize It

In medicine, more and more AI tech will be teaching highly trained clinicians to trust machines. New research suggests clinician’s trust in AI could depend on how a model explains its predictions.

As more research continues to illuminate automation bias with the use of AI tools, Paul Yi, MD, is looking toward addressing the problem. “How do we set regulation around it, and design methods in the lab that will help reduce these problems?” he said.

Anti-Ageing Jabs – They Can Rejuvenate Mice, But Will They Work on Humans?

A study by Greg Armstrong, MD, MSCE, shows that childhood cancer survivors represent a group who are ageing unusually quickly. While chemotherapies and radiotherapies have become increasingly efficient at curing childhood cancers, they are showing an impact on patients’ bodies as they reach middle age.

It appears that the consequence of undergoing treatments at a young age leaves them with abnormally large populations of senescent cells, which are a driving force in ageing and would normally take decades to accrue.

Armstrong is now leading a clinical trial of childhood cancer survivors to learn whether senolytics can help extend their life expectancy. The study could also show if senolytics have the potential to one day be used as a way of extending healthy lifespan in all older adults.

Scientists and Doctors Reveal How Genes are Mapping Cures for Cancer

St. Jude began its genomics work about a decade ago and now provides whole genome sequencing to between 400 and 500 patients per year. But few hospitals have the funds to fuel a WGS lab—much less to pay for each patient’s test.

Jeffery Klco, MD, PhD, uses WGS to find high mutation loads in patients, which helps determine treatment paths. “Without exaggeration, almost every week we find or report something that we didn’t really know about, some new alteration,” he said. “Sometimes they spur research opportunities.”

MEDIA

SPOTLIGHT

DR. RICHARD WEBBY ON BIRD FLU

As cases of human transmission of bird flu are on the rise, Richard Webby, PhD—Host-Microbe Interactions and Director, World Health Organization Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds—is a featured voice in the media. Webby’s research has contributed to the global understanding of bird flu and helped shape public health policies, vaccine development and pandemic preparedness efforts.

“This virus in its current form is of low risk to humans, but the situation as a whole is a little more worrying,” said Webby. “We’re giving this virus a lot of opportunities to change and that’s really where the real worry comes in. Low risk but the potential consequences are quite scary.”

Media Coverage

Click the “ ” below to explore bird flu coverage

A Dangerous Virus’: Bird Flu Enters a New Phase

Are Eggs Safe to Eat as Bird Flu Spreads?

New bird flu strain in cows spreads to Nevada dairy worker

As bird flu continues to spread, is there a vaccine for humans?

The wind may be partly to blame for bird flu spread between farms, a new study suggests

Can you get bird flu from eggs? Here are the answers to all your pressing questions.

Dairy cows infected with second version of bird flu

Bird Flu Is a National Embarrassment

2 beloved pet cats died after drinking raw milk recalled for bird flu

US Investigates Worrying

Bird Flu Strain on Duck Farm in California

SPOTLIGHT

GLOBAL PLATFORM FOR ACCESS TO CHILDHOOD CANCER MEDICINES

On February 11, St. Jude and WHO announced the launch of the Global Platform for Access to Childhood Cancer Medicines. In addition to the number of patients the Global Platform will eventually reach, another metric of success is the successful delivery of the first shipments of medicines to countries in need. Media coverage highlights the transformative step in global health and the potential to make a significant impact on global survival rates for pediatric cancer.

“ A child’s chances of surviving cancer are largely determined by where they are born, making this one of the starkest disparities in global healthcare. ”

James R. Downing MD, President and CEO

“ We are making excellent progress. There is every reason to think that the platform is going to be a success. ”

Carlos Rodriguez-Galindo Chair of the Department of Global Pediatric Medicine at St. Jude Children’s Research Hospital and Director of St. Jude Global

WHO, St. Jude launch groundbreaking international delivery of childhood cancer medicines

• St. Jude and WHO are making history with the first international shipments of childhood cancer medicines to under-resourced countries.

• The groundbreaking effort is starting in Mongolia, Uzbekistan, Nepal, Ecuador, Jordan, and Zambia.

• Over the next several years, the initiative will scale up to 50 countries, bringing life-saving treatments to 120,000 children.

• This is a major step toward closing the gap in childhood cancer survival rates worldwide.

The press release drove earned media and led to 87 placements with a reach of 235 million.

Sharing stories of impact and discovery across the St. Jude research enterprise.

Scientific advances make the mission of St. Jude Children’s Research Hospital possible every day. St. Jude Progress tells the stories of those advances from the investigators, laboratory researchers and clinical scientists who are making them.

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