THE LANCET
Healthy lifestyle associated with reduced mortality risk in childhood cancer survivors
• Despite huge improvements in five-year survival, adult survivors of pediatric cancer have four times the risk of death as the general population.
• Based on data from the Childhood Cancer Survivor Study (CCSS), St. Jude researchers found that a healthy lifestyle was associated a significantly reduced risk of death in survivors.
• Promoting healthy behaviors including effective prevention and control of cardiovascular disease risk factors demonstrated improvement in survivor’s health space and lifespan.
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Stephanie Dixon, MD, MD, MPH Yutaka Yasui, PhD Greg Armstrong, MD, MSCE
Q4FY23: SELECT SCIENTIFIC
DISCOVERIES
NATURE
Humans vs. bacteria: differences in ribosome decoding revealed
• Ribosomes are molecular machines within cells responsible for synthesizing proteins by decoding messenger RNA (mRNA). Change in mRNA decoding accuracy have been linked to aging and disease.
• Comprehensive studies of human ribosomes are necessary to identify new treatments for cancer and viral infections.
• St. Jude scientists used state-of-the-art structural biology tools and techniques to examine the human ribosome decoding mechanism. They uncovered key differences between bacterial and human ribosomes that reveal new potential therapeutic targets.
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Scott Blanchard, PhD
NATURE
SWI/SNF complexes “bookmark” cell identity during division
• The SWI/SNF complex is one of several factors that control chromatin architecture to regulate gene expression. Abnormalities in the SWI/SNF complex are found in approximately 20% of all cancers, and in several types of neurodevelopmental disorders.
• Using pediatric rhabdoid tumors as a model, St. Jude scientists have uncovered a previously unappreciated role for SWI/SNF complex subunits in mitotic regulation. When a cell divides, it retains information, or ‘memory’, about how to grow and what time of cell to become.
• Researchers discovered how subunits of SWI/SNF act as “bookmarks” during cell division to safeguard cell identity. Loss of SWI/SNF complex subunits in pediatric cancers may be a key component that enables cells to stay in a cancerous state.
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Charles W. M. Roberts, MD, PhD
NATURE
Epigenetic landscape modulates pioneer transcription factor binding
• DNA is tightly wound around proteins called histones and packaged into structures called nucleosomes. Changes in the structure of these elements are implicated in many cancers.
• St. Jude scientists explored how certain proteins in a cell access tightly wound DNA to alter the expression of genes. The work reveals how changes in the genetic blueprint, beyond the discrete sequence of DNA (‘epigenetics’), can influence protein interactions in a cell.
• Understanding the basic mechanisms of how proteins control the expression of genes may reveal potential therapeutic avenues for pediatric cancer and other diseases.
Mario Halic, PhD
CELL Capturing transporter structure paves the way for drug development
• Substances are escorted across cellular membranes by transporters. One of these substances, sphingosine-1-phosphate (S1P), regulates the immune system, mediates blood vessel formation, and aids in the progression and survival of cancer cells.
• Using sophisticated microscopy approaches, St. Jude scientists revealed the structure of the transporter that mediates S1P function.
• The researchers identified a small molecule inhibitor that blocks the function of the S1P transporter, revealing new avenues for therapeutic development.
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Chia Hsueh Lee, PhD
CELL St. Jude finds NLRP12 as a new drug target for infection, inflammation and hemolytic diseases
• Many diseases including malaria, SARS-CoV-2 virus infection, or sickle cell disease cause red blood cells to rupture (‘hemolysis’) and release hemoglobin, the oxygen-binding molecule.
• Heme, or degraded hemoglobin, in the bloodstream is associated with increased inflammation and multi-organ failure. St. Jude scientists discovered the key detector of heme that turns on this inflammatory cell death.
• This work was the first to identify a potential druggable target to reduce inflammation caused by infection and hemolytic diseases.
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Thirumala-Devi Kanneganti, PhD
LANCET ONCOLOGY Clinical trial improves neurocognitive outcomes for childhood craniopharyngioma
• Craniopharyngioma is a rare pediatric brain tumor typically treated with traditional radiation therapy. Despite improved survival rates, patients experiencing a high risk of neurological deficits.
• A St. Jude Phase 2 clinical trial treat patients with proton therapy, an alternative to conventional radiotherapy that decreases the amount of normal brain tissue exposed to radiation.
• Patients treated with proton therapy achieved similar survival with fewer cognitive side effects. This work suggests that proton therapy should be the new ‘gold standard’ treatment for craniopharyngioma.
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Thomas Merchant, DO, PhD
Heather Conklin, PhD
NATURE BIOMEDICAL ENGINEERING
Prime editing shows proof of concept for treating sickle cell disease
• Sickle cell disease is a serious blood disorder affecting millions of people and caused by a mutation in a subunit of the gene encoding the oxygen-carrying molecule, hemoglobin.
• St. Jude researchers used a groundbreaking gene editing approach, ‘prime editing’, to correct the mutation in blood stem cells from SCD patients. When these cells were transplanted into a preclinical model of SCD, 45% of circulating red blood cells had the healthy form of hemoglobin.
• The work provides proof of concept for how genome ‘prime editing’ might be more effective than conventional genetic editing and could lead to cures for genetic anemias.
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Mitch Weiss, MD, PhD
NATURE COMMUNICATIONS
St. Jude targets cancer-causing fusions’ weak spot
• For decades, scientists have observed mutations that combine two genes, resulting in the creation of a hybrid protein that drives cancer (fusion oncogenes).
• Many cancers depend on these fusion proteins to survive and targeting them with drugs is challenging because each individual protein is critical in healthy cells.
• Scientists at St. Jude have developed a computational tool, much like a periodic table for types of oncogenic fusions, that reveals more detail about the genetic sequence of fusion proteins.
• Researchers provided proof-of-principle that highly specific genome editing, using the CRISPR-Cas9 system and data from their computational tool, can inhibit cancer growth in cellular models.
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Xiaotu Ma, PhD
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NATURE COMMUNICATIONS
St. Jude tool gets more out of multi-omics data
• Many cancers have ‘hidden’ drivers that could be targeted therapeutically if they could be identified.
• St. Jude scientists have uncovered, within multi-omics datasets, difficult-to-identify proteins that drive biological processes contributing to cancer.
• Using advanced computational tools and technologies, the researchers found ‘hidden’ drivers, many that are targets of FDA approved drugs. These findings could facilitate faster movement into clinical trials or become the basis of novel drug development.
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Jiyang Yu, PhD
SCIENCE ADVANCES
Method for improving seasonal flu vaccines also aids pandemic prediction
• Researchers at St. Jude have discovered why the seasonal influenza vaccine varies in effectiveness year to year, and how public health specialists might better predict pandemic potential in new flu strains.
• Hemagglutinin is a small protein that projects from the surface of a virus, and acts like a mousetrap, ready to poke into a human cell in the right acidic conditions.
• Mutations in hemagglutinin can cause increased or decreased stability of the protein. Researchers showed that testing the stability of hemagglutinin might improve the seasonal flu vaccine and help predict whether novel influenza strains have pandemic potential.
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Charles Russel, PhD Richard Webby, MD
PNAS Combination therapy overcomes BET inhibitor resistance
• Inhibitors of the Bromodomain and extra-terminal domain (BET) protein have been shown to provide therapeutic benefit in patients with certain types of pediatric cancer. Unfortunately, many patients develop resistance to these compounds.
• Scientists at St. Jude revealed the importance of the SPOP gene in mediating resistance to BET inhibitors. They used next-generation gene editing technology to uncover this mechanism.
• Researchers used combination drug screening to evaluate drug combinations in preclinical models of pediatric leukemias. They found that combining BET inhibitors with GS3K inhibition may hold promise for further development.
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Chunliang Li, PhD Jun J. Yang, PhD
St. Jude scientist M. Madan Babu elected to the Royal Society of London
Director of the Center of Excellence for Data-Driven Discovery at St. Jude Children’s Research Hospital named a fellow of the elite 360-year-old British scientific organization. Babu was selected to join the Royal Society for his pioneering data sciencebased strategies to reveal fundamental principles in biological systems. His scientific accomplishments include determining the molecular mechanisms governing G-protein-coupled receptor (GPCR) signaling, uncovering the roles of disordered protein regions in biology and disease, and establishing genome-scale principles of gene regulation.
Greg Armstrong, M.D., MSCE, named Chair of the Department of Epidemiology and Cancer Control at St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital has named Greg Armstrong, M.D., MSCE, the new chair of the Department of Epidemiology and Cancer Control, the department that has established the institution as a world leader in the study of childhood cancer survivorship. Armstrong assumes the position at a critical time for St. Jude as it continues to invest heavily in research to reduce the toxicity of cancer therapy and enhance the quality of life for all pediatric cancer survivors as part of the institution’s $12.9 billion strategic plan.
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Q4FY23: ANNOUNCEMENTS
Victor J. Torres, PhD, named chair of newly formed Department of HostMicrobe Interactions at St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital announced that Victor J. Torres, Ph.D., an internationally renowned microbiologist and immunologist, has been selected as the inaugural chair of a new Department of HostMicrobe Interactions. A world leader in microbiology and host-pathogen interactions, Torres’s research efforts have focused on interactions between pathogenic bacteria and the mammalian host, with an emphasis on multidrug-resistant bacteria.
Damon Runyon launches new pediatric cancer fellowship in partnership with St. Jude Children’s Research Hospital
The Damon Runyon Cancer Research Foundation and St. Jude Children’s Research Hospital announced a new pediatric-focused fellowship. The initiative aims to help address the critical shortage of top young scientists who often seek more prevalent opportunities in adult cancer research or the pharmaceutical sector.
The Damon Runyon–St. Jude Pediatric Cancer Research Fellowship will fund up to 25 fellowships over eight years, a $9 million investment.
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Biostatistician Deo Kumar Srivistava, PhD, named ASA fellow
St. Jude Children’s Research Hospital data scientist Deo Kumar Srivistava, Ph.D., has been elected as a fellow of the American Statistical Association (ASA), the largest and oldest professional statistical organization in the world. Srivastava was selected for his outstanding contributions toward advancing pediatric cancer research using sound biostatistical methods, providing leadership and mentoring, for excellent and sustained contributions to the field of statistical methods, and for dedicated service to the profession, according to his fellowship citation.
St. Jude in top five of elite ranking of hospitals treating children with cancer
St. Jude Children’s Research Hospital is ranked again among the top five pediatric cancer hospitals on U.S. News & World Report’s 17th Annual “Best Children’s Hospitals” list released today. The U.S. News Best Children’s Hospitals rankings rely on clinical data and an annual survey of pediatric specialists. The study factors in clinical resources such as bone marrow transplantation services, brain tumors and sarcomas programs and FACT accreditation (for cellular therapy). The survey also evaluates compliance with best practices and patient outcomes, such as mortality and infection rates.
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When people think of virology, rarely do they think of a week at the beach. However, one of the most consequential long-running virological expeditions traverses the East Coast — from Memphis to Delaware Bay every May — and has for the last 38 years.
The trip began decades ago, when Robert G. Webster, PhD, emeritus faculty of the St. Jude Department of Infectious Diseases, discovered the
source for all influenza (affecting humans and other animals) was in wild birds. As birds are the natural host of influenza, he planned an annual St. Jude trip to collect samples. Webster needed
to identify a place with a high concentration of these animals to ensure flu would be present. He found it in Delaware Bay.
By returning to Delaware Bay every year, the St. Jude team has built an invaluable treasure trove of data. Dr. Richard Webby, PhD, and his team will continue working with the viruses throughout the year. The trip has produced multiple scientific discoveries, including understanding how birds spread influenza across the globe, recognizing how Delaware Bay is a “hot spot” for virus-host interactions and how virus-host interactions happen in birds to keep infections mostly asymptomatic.
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Q4FY23: FEATURED MEDIA COVERAGE
