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CONTENTS 2

Sharing our Stories

Select Scientific Discoveries

11 Faculty Honors and Awards 16 Media Spotlights

SHARING OUR STORIES This quarter highlighted the full spectrum of St. Jude excellence — from headline-making recognitions to influential scientific discoveries and global research impact. St. Jude investigators earned some of the highest honors in biomedical science, including election to the National Academy of Medicine and a record-setting presence on the Highly Cited Researchers list, underscoring the institution’s leadership and visibility on the world stage. At the same time, teams delivered advances across immune regulation, neurological disease, cancer biology, infectious disease, and therapeutic innovation, while introducing transformative technologies that expand what scientists can measure, predict, and target. Together, these honors, discoveries, and technological breakthroughs reflect a quarter defined by momentum, impact, and the continued translation of pioneering science into knowledge that shapes the future of biomedical research.

SELECT SCIENTIFIC

D I S C OV E R I E S

Mitochondria and lysosomes reprogram immune cells that dampen inflammation Hongbo Chi, PhD

Science Immunology • Our immune system needs inflammation to fight disease, but too much can cause autoimmune or inflammatory disorders. Scientists have not fully understood how the body’s inflammation “brakes” — regulatory T cells — are controlled.

• St. Jude researchers used single-cell genetic analysis to map how regulatory T cells use energy, revealing a key interaction between mitochondria and lysosomes that shapes immune responses.

• By turning off a gene that limits lysosome activity, antitumor immune responses were boosted, uncovering new metabolic pathways that could be targeted to treat

Common genetic causes across motor neuron diseases identified Gang Wu, PhD

Translational Neurodegeneration • ALS and hereditary spastic paraplegia (HSP) are related motor neuron diseases, but their genetic causes have long been considered to be distinct, making diagnosis and care more complicated.

• Researchers at St. Jude and the University of Miami Miller School of Medicine analyzed a diverse group of patients and cataloged hundreds of ultrarare gene variants to see whether the two conditions share genetic risk.

• They discovered meaningful genetic overlap between ALS and HSP, showing that some variants appear in both diseases. This insight can improve how clinicians interpret genetic tests and tailor care for people with some forms of motor neuron diseases.

autoimmune diseases, inflammation, and cancer.

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

Approach to combat antibiotic resistance turns bacterium’s genes against it

Abnormal transport signal on mutant UBTF gene drives high-risk acute myeloid leukemia

Richard Lee, PhD

Jeff Klco, MD, PhD | Richard Kriwacki, PhD

Nature Microbiology

Blood Cancer Discovery

• Mycobacterium abscessus causes chronic, hard-to-treat

• A rare, high-risk form of acute myeloid leukemia (AML)

infections because it resists many antibiotics, leaving

is driven by abnormal repeated segments in the UBTF

patients with few effective treatment options outside of

gene, leading to cancers that resist treatment and often

long-term antibiotic exposure.

relapse.

• St. Jude scientists redesigned the antibiotic florfenicol

• Researchers discovered that these repeated segments

so that it becomes active only inside a bacterium, using a

create an unusual “transport signal” that pulls in a protein

microbe’s own resistance machinery to trigger a powerful

called Exportin-1, which then shuttles the mutant UBTF to

antibacterial response.

the wrong genes and switches them on.

• This targeted “prodrug” approach boosts antibiotic

• Blocking Exportin-1 reversed this harmful activity,

effectiveness while reducing side effects and protecting

revealing a promising new therapeutic strategy for

the healthy microbiome — and could be paired with

treating this hard-to-manage subtype of AML.

existing antibiotics to deliver a knockout strategy against drug-resistant infections.

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

Data-driven risk stratification guides childhood brain tumor treatment, reducing side effects Giles Robinson, MD | Xin Zhou, PhD

Cancer Research | Neuro-Oncology • Medulloblastoma (MB) treatments like radiation and

Kinase atlas uncovers hidden layers of cell signaling regulation Aseem Ansari, PhD

Science • Cells rely on a molecular machine called RNA polymerase II to turn genes on, and scientists long believed that only

chemotherapy can cause long-term side effects in

a couple of the protein’s amino acid tail mattered for

children, yet the disease is so biologically diverse that

controlling this process.

it is hard to know which patients truly need the most aggressive therapy.

• St. Jude researchers discovered that at least 117 different kinases can modify this tail — a process called

• St. Jude scientists’ analysis of clinical, molecular, and survival data from nearly 900 patients across three major trials identified new risk groups based on tumor features such as chromosome changes, methylation patterns, and MYC amplification.

phosphorylation — far beyond the two previously emphasized positions.

• The researchers also showed that EGFR, a cancer-linked kinase usually found at the cell surface, can move into the nucleus to phosphorylate RNA polymerase II.

• This new risk-stratification strategy could allow about 40% of patients to safely receive less radiation

• This work reveals RNA polymerase II as a major control

and less chemotherapy while maintaining excellent

point for many signaling pathways, opening new

survival rates, and is now available through the MB-meta

possibilities for understanding and treating diseases,

portal to guide future trials and improve long-term

including certain cancers.

quality of life for survivors.

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

Gene therapy for sickle cell and B-thalassemia works by disrupting three-dimensional genome structure

AlphaSync database keeps protein structure prediction resource up to date

Jian Xu, PhD

Madan Babu Mohan, PhD, FRS

Blood

Nature Structural & Molecular Biology

• Current CRISPR gene therapies for sickle cell disease

• Predicting protein structures is crucial for understanding

and β-thalassemia work by shutting down a gene called

how proteins work and how diseases arise, but existing

BCL11A, but scientists did not fully understand why the

tools like AlphaFold do not keep their 200+ million

editing was so effective.

predictions updated when new protein sequences are discovered.

• Researchers at St. Jude and Northwestern University discovered that CRISPR does not just cut DNA — it

• To address this, St. Jude developed AlphaSync, a database

disrupts a complex 3D genome structure that BCL11A

that automatically generates new, up-to-date structure

needs to function, switching the defunct gene off and

predictions as soon as new sequences appear, and adds

allowing fetal hemoglobin to take over.

rich biological details such as interaction networks and surface features.

• The team also found that targeting a special RNA involved in this structure can achieve the same effect,

• With a simpler interface and continuously refreshed data,

pointing to a simpler, more accessible treatment strategy

AlphaSync helps researchers avoid errors and makes

for patients.

advanced protein-structure analysis easier and more accessible, accelerating discoveries that can improve human health.

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

St. Jude method democratizes access to T-cell receptor analysis Victor Torres, PhD | Paul Thomas, PhD

Nature Methods • T cells help the body remember and fight infections and cancers, but existing technologies cannot easily capture the full diversity of a person’s T-cell receptors — especially the paired halves that determine how each T cell recognizes threats.

• St. Jude developed TIRTL-seq, a method that dramatically lowers costs and allows millions more T cells to be analyzed at once, while accurately identifying how the two halves of each receptor pair together.

• By sequencing 10 million cells for just 10% of the cost of current best methods, TIRTL-seq provides the most complete T-cell repertoire view to date — a breakthrough that can speed discoveries and improve immune-based diagnostics and therapies.

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

Inflammation and metabolic stress combine to drive a new cell death pathway: mitoxyperilysis Thirumala-Devi Kanneganti, PhD

Cell • Infections and cancers trigger inflammation and excessive nutrient consumption , but scientists have traditionally studied these stresses separately, limiting understanding of how they can jointly affect cells.

• St. Jude researchers studied immune activation together with nutrient starvation and discovered a new type of inflammatory cell death called mitoxyperilysis, driven by damaged mitochondria causing oxidative stress at the cell membrane.

• They showed that activating mitoxyperilysis can shrink tumors in mice, revealing a novel therapeutic strategy and highlighting how combining immune and metabolic insights can uncover powerful new biology.

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

Research reveals structural mechanism behind anti-epilepsy therapies Chia-Hsueh Lee, PhD

Nature Communications • SV2A, a protein present in nearly all neurons, is targeted by widely used anti-epilepsy drugs, but little was known about how these drugs interact with the protein.

• St. Jude and UT Southwestern researchers mapped the structural changes in SV2A when drugs bind and studied how experimental compounds attach to an alternative site to boost drug effectiveness.

• These insights reveal how SV2A-targeting drugs work at the molecular level and provide guidance for designing more potent and optimized therapies for epilepsy.

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

F A C U LT Y H O N O R S

A N D AWA R D S

St. Jude scientist named to STAT Wunderkind class of 2025 for research contributions Andrew Kleist’s recognition as a 2025 STAT Wunderkind highlights his groundbreaking contributions to understanding molecular protein behavior, advancing research that could transform therapies for infectious diseases, cancer, and genetic disorders.

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

2025 Highly Cited Researchers list highlights St. Jude scientific impact

A record‑high 18 scientists at St. Jude were named to the 2025 Highly Cited Researchers list — marking the largest class in the institution’s history and spotlighting individuals whose work ranks in the top 1% of citations worldwide.

Learn more: Visit the St. Jude

Newsroom to read the full press release.

Two investigators honored with election to the National Academy of Medicine

Election to the National Academy of Medicine is one of the highest honors in U.S. biomedical science, reserved for individuals whose research, leadership, and innovation have had a transformative impact on health and medicine.

P. David Rogers was elected to the National Academy of Medicine in recognition of his pioneering research on the emergence of antifungal drug resistance, advancing understanding of infectious disease biology and treatment strategies.

J. Paul Taylor was elected to the National Academy of Medicine for his groundbreaking work on protein condensation and its role in neurological disease, providing critical insights into disease mechanisms and potential therapies.

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

MEDIA

S P OT L I G H T S

Continuing Coverage:

Influenza Trends As the U.S. reports its first confirmed human death from a rare bird-flu strain (H5N5 avian influenza) in November 2025 and a novel seasonal flu variant (H3N2 subclade K) spreads across the country, St. Jude influenza experts are being consulted in public health media discussions. Their insights into how these viruses behave, how likely they are to infect humans, and what that means for children has helped frame a balanced understanding of risk. By contributing scientific context when these alarming flu developments hit headlines, St. Jude is reinforcing its reputation not only as a pediatric cancer center — but also as a trusted leader in pediatric infectious-disease surveillance and research.

MEDIA COVERAGE

Landmark Study Sheds Light on Rare Pediatric Tumor Recent coverage in The Cancer Letter highlights St. Jude Children’s Research Hospital’s landmark study on infant-type hemispheric glioma, providing the largest genomic and clinical characterization to date of this rare pediatric brain tumor. The findings identify molecular drivers and potential therapeutic targets, reinforcing St. Jude’s role in advancing precision medicine approaches for challenging childhood cancers.

Largest study of infant-type hemispheric glioma reports factors to guide approaches Neuro-Oncology Aditi Bagchi, MD, PhD St. Jude researchers and international partners studied 164 cases of a rare, aggressive brain tumor in infants and found that surgery, while risky, can significantly improve survival when successful. This work lays the groundwork for safer, more effective treatment approaches for these vulnerable patients. Learn more: Visit the St. Jude Newsroom to read the full press release.

Voices of

St. Jude

The Big Unlock

This quarter’s podcast and radio coverage spotlighted

featuring Paul Yi, MD

the breadth of St. Jude expertise — from cuttingedge innovation to community-focused care. The Big Unlock featured Dr. Paul Yi on how AI and virtual-trial imaging are advancing pediatric medicine. Degrees of Science on KWTX highlighted St. Jude leadership during Childhood Cancer Awareness Month. And on WLOK’s Let’s Talk About It, St. Jude experts elevated vital conversations around HIV and community health.

MEDIA COVERAGE

Degrees of Science Read more

with Seth Karol, MD

WHERE SUPPORT

Meets Science

In recent media coverage, the central role of child-life support and family-centered care in pediatric oncology has gained renewed attention – a domain where St. Jude continues to lead. A U.S. News article exploring the work of “child-life specialists” emphasized how these professionals can reduce stress and anxiety for young patients by using therapeutic play, age-appropriate explanations of medical procedures, and emotional support for siblings and care givers. Meanwhile, a November 2025 study of parents and children with cancer highlighted a clear demand for emotional support, peer connection, and help in navigating the treatment journey. By offering comprehensive childlife and psychosocial services alongside cutting-edge medical treatment and research, St. Jude reinforces its mission of finding cures and saving children.

MEDIA COVERAGE

St. Jude Recognized for Excellence St. Jude has consistently earned recognition as a top employer — ranked No. 2 in the U.S. by Forbes in its 2025 “Best Employers for Healthcare Professionals” list, and again among the very top in Forbes’ “America’s Dream Employers 2026.” At the same time, the hospital continues to lead in patient care excellence — recognized by U.S. News & World Report in 2025 as one of the top 10 children’s cancer hospitals for the 18th year in a row. These achievements reflect a workplace culture that combines mission-driven purpose, strong professional standards, and a collaborative environment, making St. Jude a place where dedicated clinicians, researchers, and staff can build meaningful, long-term careers while contributing to life-changing work.

MEDIA COVERAGE Read more Read more

Omics

IN FOCUS

This quarter, St. Jude’s leadership in spatial omics was featured in multiple outlets, including

Spatial Touchstone brings quality control to spatial transcriptomics

MedicalXpress, Technology Networks, and Mirage News, for its role in the Spatial Touchstone initiative. The coverage emphasized how St. Jude is not only generating cutting-edge spatial transcriptomics data but also shaping the standards and qualitycontrol practices that allow labs worldwide to produce reliable, comparable results. By advancing both the science and the reproducibility of spatial omics, St. Jude is reinforcing its position as a global leader in this rapidly evolving field.

MEDIA COVERAGE

Nature Biotechnology Jasmine Plummer, PhD The Spatial Touchstone project has created a standardized, openly available collection of gene-mapping data and tools, helping researchers ensure their experiments are highquality and comparable across labs. This work brings consistency and reliability to a rapidly growing area of cancer and biology research. Learn more: Visit the St. Jude Newsroom to read the full press release.

Proteins

in the Spotlight

Over the last few months, researchers have revealed how proteins behave in surprisingly complex ways — and how those discoveries could lead to smarter treatments. In one study, scientists detailed for the first time how two chaperone proteins (which aid in protein folding) team up to catch and refold misfolded proteins — a process that protects cells from toxic clumps linked to many diseases. Other studies showed how flexible or “disordered” protein regions can spark harmful condensates that drive cancer and how a newly identified “hidden pocket” in a nuclear receptor may help guide targeted drug design. Adding to this, broader research on “deathfold” proteins — molecular triggers of cell death — is shedding light on how cells decide whether to live or die, a mechanism relevant to both neurodegeneration and cancer. Together, the findings signal St. Jude’s growing leadership in decoding protein behavior at a deep structural level — and in transforming that knowledge into possible therapies for childhood diseases and beyond.

MEDIA COVERAGE

First complete structures of heat shock chaperone protein complex reveal handoff mechanism

Protein sidekick exhibits dual roles in stress granule assembly and disassembly

Molecular Cell Babis Kalodimos, PhD

Science Advances Mondira Kundu, MD, PhD

St. Jude scientists revealed how two key heat shock

St. Jude scientists discovered that the protein ASPL

proteins work together to manage misfolded proteins,

helps both build and break down stress granules,

which are linked to many diseases. Their detailed

which protect fragile RNA in cells. This insight

structures provide a roadmap for developing new

sheds light on how disruptions in these processes

therapies for genetic disorders, cancer, and infections.

may contribute to neurodegenerative diseases.

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

Research reveals how disordered protein regions contribute to cancer-causing condensates Science Advances Richard Kriwacki, PhD

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

Researchers find a ‘hidden pocket’ to target nuclear receptors Nature Communications Taosheng Chen, PhD

St. Jude scientists developed a machine learning tool

St. Jude scientists discovered a new pocket on nuclear

that predicts which disordered protein regions can form

receptors that can be selectively targeted by protein-

condensates, helping explain how certain fusion proteins

degrading drugs. This finding offers a way to target

drive disease. This resource will aid research into RNA biology,

individual nuclear receptors, opening new possibilities

cancer, and other disorders linked to protein condensates.

for developing safer, more effective medicines.

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

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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