DALLAS – Sept. 17, 2025 – The Liver Tumor Program at UT Southwestern Medical Center’s Harold C. Simmons Comprehensive Cancer Center has been selected by the National Cancer Institute as a Specialized Program of Research Excellence (SPORE). Accompanied by a $12 million grant over five years, the SPORE aims to speed the development of new ways to treat and prevent liver cancer.

Yujin Hoshida, M.D., Ph.D., (left) Professor of Internal Medicine and Director of Liver Tumor Translational Research, will co-lead the liver cancer SPORE at UT Southwestern with Amit Singal, M.D., M.S., Professor of Internal Medicine and in the Peter O’Donnell Jr. School of Public Health as well as Medical Director of the Liver Tumor Program and Chief of Hepatology at UTSW.

“We’re quite honored to be chosen as a liver cancer SPORE. Our selection speaks to the quality of science and the potential for discovery and advances in clinical research and care at UT Southwestern,” said Amit Singal, M.D., M.S., Professor of Internal Medicine and in the Peter O’Donnell Jr. School of Public Health as well as Medical Director of the Liver Tumor Program and Chief of Hepatology at UTSW. Dr. Singal will co-lead the liver cancer SPORE with Yujin Hoshida, M.D., Ph.D., Professor of Internal Medicine and Director of Liver Tumor Translational Research.

Dr. Singal explained that the SPORE’s overarching goal is to transform innovative scientific discoveries from UTSW into precision interventions that reduce liver cancer incidence and mortality. The effort will have a special focus on hepatocellular carcinoma (HCC), which accounts for over 85% of liver cancer cases across the nation. More than 42,000 new cases of liver cancer, including HCC, are diagnosed every year in the U.S., and more than 30,000 Americans die of liver cancer annually. Cirrhosis from heavy alcohol use, metabolic dysfunction, viral hepatitis, and some genetic variations are key risk factors for HCC and other liver cancers.

These risk factors are particularly common in Texas, which has one of the highest incidences of HCC in the country, Dr. Hoshida said. UTSW joins the Mayo Clinic and The University of Texas MD Anderson Cancer Center as liver cancer SPOREs across the nation.

“Our goal is to significantly improve liver cancer survival rates by refining the prevention and treatment of this disease through various new approaches,” he said.

The bulk of the SPORE grant will fund three research projects.

Reducing risk of developing HCC

The first, led by Drs. Singal and Hoshida, will test a promising “chemoprevention” strategy in people considered at high risk of developing HCC due to existing cirrhosis. Previous research in animal models at UTSW showed that a protein known as the epidermal growth factor receptor (EGFR) appears to foster cirrhosis-driven HCC development. By suppressing activity of this protein through an EGFR-inhibiting drug called erlotinib, researchers reduced the risk of HCC in these mouse models, a result mirrored in a recent phase one clinical trial in patients with cirrhosis. The UTSW team plans to test this strategy in a larger number of patients in a phase two trial, using a novel biomarker they discovered called a prognostic liver secretome signature as a proxy for HCC risk.

Preventing recurrence of HCC

The second project, led by Hao Zhu, M.D., Professor in Children’s Medical Center Research Institute at UT Southwestern and of Internal Medicine and Pediatrics, and David Hsieh, M.D., Associate Professor of Internal Medicine, will focus on preventing recurrence of HCC in cirrhosis patients who were previously treated. Tumors regrow within two years in about 50%-70% of these patients because the risk factors that caused the initial disease are still present, Dr. Zhu explained. Having extra chromosomes in liver cells – a condition called polyploidy – has been shown to be protective against developing HCC. Previous research in the Zhu Lab showed that reducing a protein known as anillin can induce polyploidy and reduce development of HCC. The researchers plan to test this anillin-targeting strategy in a phase one clinical trial.

Improving immunotherapy to prevent HCC recurrence

The third project, led by Daolin Tang, M.D., Ph.D., Professor of Surgery, and Adam Yopp, M.D., Professor of Surgery and Division Chief of Surgical Oncology and Surgical Director of the Liver Tumor Program, will focus on improving the efficacy of immunotherapy to prevent HCC recurrence. Although immunotherapy drugs – which harness the immune system to fight cancer – have shown promise in treating advanced stage HCC, their benefit in preventing recurrence after HCC tumors are surgically removed has been unclear. To boost their performance, the researchers plan to test these drugs in combination with a drug known as a telomerase reverse transcriptase (TERT) inhibitor. This agent has been shown to selectively stop HCC cells from multiplying and kill them while also activating a cancer-fighting subset of immune cells. A planned phase one b trial will test the safety and efficacy of the TERT inhibitor combined with immune checkpoint inhibitors in patients who will undergo surgery to remove HCC tumors.

Additional funding

Along with these projects, the SPORE grant will also fund a Developmental Research Program, which will provide seed funding to launch new high-risk, high-reward projects, and a Career Enhancement Program, which will aid early-career scientists and clinicians interested in translational liver cancer research. In addition, the grant will support three cores: an Administrative and Outreach Core, which will provide essential administrative services for the SPORE; a Biospecimen and Pathology Core, which will house patient-derived tissue and blood samples needed for research; and a Data Science Core, which will provide biostatistical and bioinformatic data analysis support to researchers.

“The successful funding of the liver SPORE is a major accomplishment of the Simmons Cancer Center. It represents an outstanding example of the multidisciplinary and collaborative science destined to have a major impact on the prevention and treatment of this lethal disease in the state of Texas and beyond as well as a testament to UTSW’s commitment for translational research,” said Carlos L. Arteaga, M.D., Director of the Simmons Cancer Center and Associate Dean of Oncology Programs at UT Southwestern.

UTSW is home to two other SPOREs for lung cancer and kidney cancer research.

Dr. Singal is a Dedman Family Scholar in Clinical Care and holds the Willis C. Maddrey, M.D. Distinguished Chair in Liver Disease. Dr. Hoshida holds the H. Ray and Paula Calvert Chair in Gastroenterology Oncology in Honor of Udit Verma, M.D. Dr. Zhu holds the Nancy B. and Jake L. Hamon Distinguished Chair in Therapeutic Oncology Research and is a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. Dr. Yopp holds The Occidental Chemical Chair in Cancer Research. Dr. Arteaga holds the Annette Simmons Distinguished University Chair in Breast Cancer Research.

Drs. Singal, Hoshida, Zhu, Hsieh, Tang, and Yopp are members of Simmons Cancer Center. Dr. Zhu is also co-leader of the Simmons Cancer Center Development and Cancer Research Program.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – Sept. 16, 2025 – A team led by UT Southwestern Medical Center scientists has identified early signals from the immune system that could help predict which cancer patients are most likely to develop harmful side effects from immunotherapy. The findings, published in the Journal for ImmunoTherapy of Cancer, offer a path toward tests to help doctors tailor care for at-risk patients.

David Gerber, M.D., is Professor of Internal Medicine in the Division of Hematology and Oncology and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern. He is also co-Director of the Office of Education and Training in the Harold C. Simmons Comprehensive Cancer Center. He holds the David Bruton, Jr. Professorship in Clinical Cancer Research.

“Through a multi-omic biomarker analysis, we identified a pre-existing but clinically silent proinflammatory state in patients with increased risk of immunotherapy toxicities,” said David Gerber, M.D., Professor of Internal Medicine in the Division of Hematology and Oncology and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern. Dr. Gerber, who is also co-Director of the Office of Education and Training in the Harold C. Simmons Comprehensive Cancer Center, co-led the study with first author Shaheen Khan, Ph.D., who was previously Assistant Professor of Pathology at UT Southwestern.

Immune checkpoint inhibitors – drugs that enhance the immune system’s ability to attack cancer – have transformed treatment for many cancers and extended lives even in patients with advanced disease. But they can also spark reactions that damage healthy organs, sometimes causing serious and lasting complications. More than half of patients receiving immunotherapy experience side effects, which remain difficult to predict or diagnose.

By analyzing blood from 162 patients at UT Southwestern and Parkland Health before and after immunotherapy treatment, researchers identified three key features linked to higher risk: elevated levels of antibody-producing cells and autoantibodies, stronger activity from inflammatory molecules such as interferon-gamma, and heightened signals from another key inflammatory molecule known as tumor necrosis factor or TNF. Patients with these immune profiles were more likely to develop side effects once treatment began.

Mitchell von Itzstein, M.D., is Assistant Professor of Internal Medicine in the Division of Hematology and Oncology at UT Southwestern and a member of the Harold C. Simmons Comprehensive Cancer Center.

“If prospectively verified, these findings potentially impact patients with any cancer types that are treated with immunotherapy,” said study co-author Mitchell von Itzstein, M.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology at UT Southwestern. “Currently, immunotherapy is used to treat most cancers in advanced stages as well as some cancers in earlier stages.”

The study builds on more than a decade of work at the UT Southwestern Simmons Cancer Center, where Dr. Gerber and other researchers have developed an institutional registry of immunotherapy patients and biospecimens. With contributions from more than 800 patients cared for at UT Southwestern and Parkland Health, the registry has enabled one of the most comprehensive efforts to date to connect immune, genetic, and antibody changes with treatment complications.

While the results are promising, the authors noted further research is needed to confirm these biomarkers in larger and more diverse groups and translate them into tools for patient care.

Jeffrey A. SoRelle, M.D., is Assistant Professor of Pathology and Pediatrics and a member of the Immunology Graduate Program at UT Southwestern.

“The prediction, diagnosis, treatment, and monitoring of immune-related side effects remain major clinical challenges,” said study co-author Jeffrey A. SoRelle, M.D., Assistant Professor of Pathology and Pediatrics and a member of the UTSW Immunology Graduate Program. “Identifying the molecular mechanisms behind these side effects may help predict which patients are at greatest risk and potentially provide guidance for the treatment of these toxicities.”

Dr. Gerber holds the David Bruton, Jr. Professorship in Clinical Cancer Research. Dr. von Itzstein is a member of the Simmons Cancer Center.

A full list of contributors and their disclosures can be found in the published study.

This study was funded by the National Institute of Allergy and Infectious Diseases (1U01AI156189-01 and K08AI155832), an American Cancer Society-Melanoma Research Alliance Team Award (MRAT-18-114-01-LIB), a V Foundation Robin Roberts Cancer Survivorship Award (DT2019-007), a Melanoma Research Alliance and Society for Immunotherapy of Cancer Young Investigator Award (619351), the University of Texas Lung Cancer Specialized Program of Research Excellence (SPORE) (P50CA070907-21), and a National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543).

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

About Parkland Health

Parkland Health is one of the largest public hospital systems in the country. Premier services at the state-of-the-art Parkland Memorial Hospital include the Level I Rees-Jones Trauma Center, the only burn center in North Texas verified by the American Burn Association for adult and pediatric patients, and a Level III Neonatal Intensive Care Unit. The system also includes two on-campus outpatient clinics – the Ron J. Anderson, MD Clinic and the Moody Outpatient Center, as well as more than 30 community-based clinics and numerous outreach and education programs. By cultivating its diversity, inclusion, and health equity efforts, Parkland enriches the health and wellness of the communities it serves. For more information, visit parklandhealth.org.

DALLAS – Sept. 11, 2025 – Steven McKnight, Ph.D., Professor of Biochemistry at UT Southwestern Medical Center, has been awarded the Albert Lasker Basic Medical Research Award for discoveries into the role of proteins of low sequence complexity and their influence on the dynamics of cell morphology and biological regulation.

Often called “America’s Nobels,” the Lasker Awards recognize significant advances in the understanding, diagnosis, treatment, cure, and prevention of human disease and are regarded as the country’s preeminent biomedical research prize. Since 1945, the Lasker Foundation has awarded more than 400 prizes.

Steven McKnight, Ph.D.

Dr. McKnight’s recognition marks the second consecutive year and fifth time that a UT Southwestern scientist has earned a Lasker Award. With this honor, he joins Zhijian “James” Chen, Ph.D. (2024), Professor of Molecular Biology and Director of the Center for Inflammation Research, and Nobel Laureates Alfred Gilman, M.D., Ph.D. (1989), Michael Brown, M.D. (1985), and Joseph Goldstein, M.D. (1985), as UT Southwestern recipients.

Dr. McKnight’s studies – focused on proteins of low sequence complexity – have revealed how these disordered proteins can reversibly self-associate to control innumerable forms of dynamic cellular organization and aggregate in a manner that leads to neurologic and neurodegenerative disease.

“His work over the past three decades has exemplified our institution’s commitment to curiosity-driven research by advancing our understanding of cellular and molecular mechanisms, which ultimately inform new approaches to disease treatment,” said Daniel K. Podolsky, M.D., President of UT Southwestern. “We are thrilled to see the importance of his fundamental discoveries into the role of low complexity proteins in basic cellular functions recognized by this year’s Lasker Basic Medical Research Award.”

Prior to the work that has garnered the Lasker Award, Dr. McKnight’s early studies of gene regulation led to the identification of the leucine zipper, a structural motif in transcription factors – proteins that regulate gene expression. This discovery helped clarify how the expression of cellular genes is turned on and off.

Teaming up with David Russell, Ph.D., Professor Emeritus and former Vice Provost and Dean of Basic Research, Dr. McKnight also discovered the HIF-2α transcription factor and identified its role in adapting cells and tissues to conditions of oxygen starvation. Working in collaboration with Richard Bruick, Ph.D., and synthetic chemists in the Biochemistry Department at UT Southwestern, Dr. McKnight discovered drug-like compounds capable of inhibiting the HIF-2α protein. In 2008, UT Southwestern licensed these chemicals to Peloton Therapeutics Inc., a Dallas-based biotechnology company founded by Dr. McKnight. Following extensive optimization and subsequent clinical trials, the chemical inhibitor of HIF-2α, designated belzutifan, was approved in 2021 by the Food and Drug Administration as a treatment for kidney cancer.

“I want to thank the Lasker Foundation for this great honor,” said Dr. McKnight, who holds the Distinguished Chair in Basic Biomedical Research at UT Southwestern. “I am also grateful to the colleagues and trainees who’ve worked with me over the years and to the leadership of UT Southwestern, who have created the environment for scientists to probe challenging and important questions.”

A former Howard Hughes Medical Institute Investigator, Dr. McKnight is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. Other honors include the Robert A. Welch Award in Chemistry (2020), the Wiley Prize in Biomedical Sciences (2014), the National Institutes of Health Director’s Pioneer Award (2004), the Monsanto Award from the National Academy of Sciences (1991), and the Eli Lilly Award from the American Society for Microbiology (1989).

Dr. McKnight earned a bachelor’s degree in biology from the University of Texas at Austin, followed by a Ph.D. in biology from the University of Virginia. He did postdoctoral research at the Carnegie Institution of Washington before joining UT Southwestern in 1995. He is a member of the Harold C. Simmons Comprehensive Cancer Center.

Dr. McKnight shares the 2025 Albert Lasker Basic Medical Research Award with Dirk Görlich, Ph.D., a German biochemist who is director of the Max Planck Institute for Multidisciplinary Sciences. Dr. Görlich is also being honored for his work on proteins of low sequence complexity.

The Lasker Awards will be presented in New York on Sept. 19.

Dr. Brown is a Regental Professor and holds the W.A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research and the Paul J. Thomas Chair in Medicine.

Dr. Chen holds the George L. MacGregor Distinguished Chair in Biomedical Science.

Dr. Goldstein is a Regental Professor and holds the Julie and Louis A. Beecherl, Jr. Distinguished Chair in Biomedical Research and the Paul J. Thomas Chair in Medicine.

Dr. Podolsky holds the Philip O’Bryan Montgomery, Jr., M.D. Distinguished Presidential Chair in Academic Administration and the Charles Cameron Sprague Distinguished Chair in Biomedical Science.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – Sept. 9, 2025 – Zhijian “James” Chen, Ph.D., Professor in the Department of Molecular Biology at UT Southwestern Medical Center and one of the world’s top researchers on innate immunity, has been awarded the 2026 Elaine Redding Brinster Prize in Science or Medicine in recognition of his discovery of the cGAS enzyme and its role in immune response.

“I am extremely honored and humbled to be selected as the fifth recipient of the Elaine Redding Brinster Prize,” said Dr. Chen, who is a Howard Hughes Medical Institute Investigator and Director of the Center for Inflammation Research at UT Southwestern. “This prize is very special not only because Dr. Ralph Brinster is one of my scientific heroes but also because it epitomizes the key role of family support in the success of a scientist. I myself have benefited from the strong support of my family, as well as my colleagues and mentors. This prize is a recognition of the hard work and dedication of the researchers, trainees, and staff members in my lab who have contributed to the discoveries of cGAS and other molecules involved in our body’s immune defense.”

The Brinster Prize is awarded annually by the Institute for Regenerative Medicine at the University of Pennsylvania to a researcher whose discovery has made a unique impact on biomedicine. It is supported by an endowment from the children of Elaine Redding Brinster and Ralph L. Brinster, V.M.D., Ph.D., the Richard King Mellon Professor of Reproductive Physiology at the University of Pennsylvania and a National Medal of Science recipient.

Announcing the award, Penn Medicine said Dr. Chen’s research has “opened up a new area of science by showing how our immune system spots harmful DNA from germs, like bacteria and viruses, and starts fighting them.”

Dr. Chen’s discoveries include MAVS, the first mitochondrial protein known to be involved in immunity against infections. The protein’s name both describes its function (mitochondrial antiviral signaling) and honors his favorite basketball team, the Dallas Mavericks. In 2012, his laboratory identified cGAS (cyclic GMP-AMP synthase), which triggers the innate immune system when it detects foreign DNA inside a cell. He and his colleagues are now studying the complex biochemical pathways by which cGAS works.

Dr. Chen’s research has been recognized with some of the most esteemed awards in science, including the Albert Lasker Basic Medical Research Award (2024), the Louisa Gross Horwitz Prize (2023), and the Breakthrough Prize in Life Sciences (2019).

Dr. Chen is a member of both the National Academy of Sciences and the National Academy of Medicine. At UTSW, he is a member of the Center for the Genetics of Host Defense as well as the Harold C. Simmons Comprehensive Cancer Center. He holds the George L. MacGregor Distinguished Chair in Biomedical Science.

The Brinster Prize will be presented March 18, 2026, as part of the daylong Ralph L. Brinster Symposium at Penn’s Philadelphia campus. The prize comes with an award of $200,000.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – Aug. 04, 2025 – A team led by UT Southwestern Medical Center scientists has identified a specific stage of neurodevelopment when differentiating neural cells produce fewer ribosomes, which are responsible for making proteins. This subsequent drop in protein production, they report in Nature Cell Biology, helps explain why mutations that further affect ribosome production can cause neurodevelopmental disorders.

Michael Buszczak, Ph.D., is Professor of Molecular Biology and a member of the Development and Cancer Research Program in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He holds the Lillian B. and Tom B. Rhodes Professorship in Stem Cell Research and is an E.E. and Greer Garson Fogelson Scholar in Medical Research. 

“We find that ribosome levels decrease during neuroepithelial differentiation, a very early step in human brain development, making differentiating cells particularly vulnerable to changes in ribosome biogenesis during this time,” said Michael Buszczak, Ph.D., Professor of Molecular Biology at UT Southwestern.

Dr. Buszczak co-led the study with UT Southwestern collaborators Jun Wu, Ph.D., Associate Professor of Molecular Biology; Chunyang Ni, Ph.D., a former researcher in the Buszczak Lab who is now at Stanford University; and Yudong Wei, Ph.D., postdoctoral fellow in the Buszczak Lab. International collaborators were Barbara Vona, Ph.D., Group Leader of the Institute for Auditory Neuroscience at University Medical Center Gottingen in Germany, and Reza Maroofian, Ph.D., Research Fellow at University College London.

The researchers homed in on a group of neurodevelopmental disorders that share a set of features, including severe intellectual disability, low muscle tone, hearing and vision impairment, and small brain size. These disorders are linked to mutations in a gene known as AIRIM that plays a key role in generating ribosomes. But how the genetic mutations cause these features has been unknown.

Working with the Wu Lab – which specializes in creating model systems called organoids that replicate the development of organs – the researchers genetically manipulated cells carrying the genetic defects to revert into stem cells that formed brain organoids. For comparison, they did the same with defect-free cells.

Jun Wu, Ph.D., is Associate Professor of Molecular Biology at UT Southwestern and a Virginia Murchison Linthicum Scholar in Medical Research. 

They then tracked the organoids’ development. By day 15 – a crucial point in which specific descendants of stem cells called neuroepithelial cells transition into more specialized cells called radial glia – organoids made from mutated cells were smaller and more of their cells died.  

A closer look showed that cells in both types of organoids made fewer ribosomes during this time. However, organoids carrying mutations in AIRIM had even fewer ribosomes than normal. Subsequent experiments showed that this dearth of ribosomes in the mutated organoids led their cells to produce lower levels of certain proteins, particularly those involved in cell survival and cell differentiation.

By genetically or pharmaceutically prompting cells to increase the activity of mTOR – a protein that encourages protein production – the researchers “rescued” the cells carrying the genetic defects. These cells then formed organoids of the same size and similar protein production to those made of nonmutated cells. Dr. Buszczak suggested that a similar intervention could someday be used to treat some neurodevelopmental disorders caused by ribosome deficiencies in patients before they’re born, potentially sparing them from the symptoms of these neurodevelopmental conditions. He and his colleagues plan to investigate whether the symptoms of other neurodevelopmental disorders caused by genetic mutations in ribosome-related genes are connected to similar natural dips in ribosome production during development.

UTSW researchers who contributed to this study are Chao Xing, Ph.D., Professor in the Eugene McDermott Center for Human Growth and Development, the Lyda Hill Department of Bioinformatics, and the Peter O’Donnell Jr. School of Public Health; Matthew Sieber, Ph.D., Assistant Professor of Physiology; Yan Liu, Ph.D., and Ashwani Kumar, M.S., Computational Biologists; Yi Ding, Ph.D., Research Associate; Masahiro Sakurai, Ph.D., Research Scientist; Emily Ballard, B.S., graduate student researcher; and Leijie Li, Ph.D., and Shenlu Qin, Ph.D., postdoctoral researchers.

Dr. Buszczak holds the Lillian B. and Tom B. Rhodes Professorship in Stem Cell Research and is an E.E. and Greer Garson Fogelson Scholar in Medical Research. He is also a member of the Development and Cancer Research Program in the Harold C. Simmons Comprehensive Cancer Center. Dr. Wu is a Virginia Murchison Linthicum Scholar in Medical Research. 

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – July 29, 2025 – UT Southwestern Medical Center is the No. 1 hospital in Dallas-Fort Worth for the ninth consecutive year and ranks among the nation’s top hospitals for care in 12 specialties – the most of any hospital in Texas, according to U.S. News & World Report’s annual Best Hospitals list released today.

UT Southwestern ranks in the top 10 nationwide for Neurology & Neurosurgery and is among the top 25 in eight other specialties: Cancer; Cardiology, Heart & Vascular Surgery; Diabetes & Endocrinology; Ear, Nose & Throat; Geriatrics; Pulmonology & Lung Surgery; Rehabilitation; and Urology. In addition, UT Southwestern is rated “High Performing” in the great majority of evaluated conditions and procedures, from aortic valve surgery and hip fracture to back surgery (spinal fusion) and stroke care.

“This recognition reflects the expertise, collaboration, and commitment to providing the very best care possible to our patients – a standard of excellence that extends across all we do, from educating future leaders in science and medicine to advancing discovery and providing exceptional care,” said Daniel K. Podolsky, M.D., President of UT Southwestern Medical Center.

UT Southwestern is ranked among the nation's top hospitals for care in 12 specialties — the most of any hospital in Texas.

Among more than 4,400 hospitals reviewed by U.S. News, all data-driven specialties at UT Southwestern are nationally ranked. UTSW is among the top 50 nationwide in the following 12 specialties and continues to lead the state with the most nationally ranked specialties of any hospital in Texas:

• No. 9: Neurology & Neurosurgery
• No. 15: Rehabilitation
• No. 16: Geriatrics
• No. 16: Pulmonology & Lung Surgery
• No. 18: Diabetes & Endocrinology
• No. 20: Cancer
• No. 20: Cardiology, Heart & Vascular Surgery
• No. 21: Ear, Nose & Throat
• No. 24: Urology
• No. 26: Gastroenterology & GI Surgery
• No. 29: Orthopedics
• No. 37: Obstetrics & Gynecology

UT Southwestern ranks No. 2 among all hospitals in Texas and is top-ranked in the state for Neurology & Neurosurgery and Geriatrics care. Among 22 procedures and conditions evaluated by U.S. News, UT Southwestern is designated High Performing in: abdominal aortic aneurysm repair; aortic valve surgery; back surgery (spinal fusion); chronic obstructive pulmonary disease (COPD); colon cancer surgery; diabetes; gynecological cancer surgery; heart arrhythmia; heart attack; heart failure; hip fracture; kidney failure; leukemia, lymphoma, and myeloma; lung cancer surgery; pneumonia; prostate cancer surgery; and stroke. 

Additionally, the Southwestern Health Resources network – which aligns the strengths of UT Southwestern with those of Texas Health Resources – has five of the nine top-ranked hospitals in Dallas-Fort Worth. In addition to UT Southwestern at No. 1, Texas Health Presbyterian Hospital Dallas ranked No. 5, Texas Health Harris Methodist Hospital Fort Worth ranked No. 6, Texas Health Presbyterian Hospital Plano ranked No. 7, and Texas Health Harris Methodist Hospital Southwest Fort Worth ranked No. 9. The patient-centered, clinically integrated network of 31 hospital locations and more than 7,000 physicians and other providers cares for millions of individuals across 16 counties in North Texas. Children’s Medical Center Dallas, where the UT Southwestern Pediatric Group practices, was rated among the nation’s best pediatric hospitals by U.S. News for 2024-25 and was the only pediatric hospital in North Texas ranked in all 11 specialties.

Growing to meet the needs of patients

UT Southwestern continues to expand its clinical footprint to meet the health care needs of patients in fast-growing North Texas.  

Construction is underway on a $177 million Radiation Oncology campus in Fort Worth. The 65,000-square-foot facility will include the city’s first MRI-guided precision radiation treatment.

Last fall, UT Southwestern and Children’s Health broke ground on a transformative $5 billion pediatric campus in Dallas’ Southwestern Medical District across from William P. Clements Jr. University Hospital, significantly expanding inpatient, surgical, and ambulatory capacity to meet the needs of one of the country’s fastest-growing and largest metropolitan areas. The new campus will serve as a collaborative center for innovation, academic research, training, and the advancement of lifesaving technologies.

Additionally, in recent years, UT Southwestern opened UT Southwestern Medical Center at RedBird to improve access to care for those living and working in southwestern Dallas County, as well as a regional medical center in Coppell and a nine-story Cancer Care Outpatient Building to serve patients of the Harold C. Simmons Comprehensive Cancer Center.  

Other recent national distinctions

• Clements University Hospital was honored earlier this year for patient experience with Press Ganey’s Guardian of Excellence Award, and UTSW’s Multi-Specialty Clinic earned the Pinnacle of Excellence Award.
• UT Southwestern Medical School is ranked in Tier 1 (top 16) for research and Tier 2 (top 50) for primary care by U.S. News in its 2025 Best Medical Schools rankings. The UT Southwestern Graduate School of Biomedical Sciences and the School of Health Professions also have nationally rated programs.
• UT Southwestern is ranked No. 2 in the world for Endocrinology & Metabolism research and among the top 50 in seven other fields by U.S. News in its 2025-26 Best Global Universities report. Also, UT Southwestern is ranked No. 1 among global health care institutions by Nature Index for publishing high-quality research in biological sciences.

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – July 28, 2025 – A multidisciplinary team at UT Southwestern Medical Center has developed an artificial intelligence (AI)-enabled pipeline that can quickly and accurately extract relevant information from complex, free-text medical records. The team’s novel approach, featured in npj Digital Medicine, could dramatically reduce the time needed to create analysis-ready data for research studies.

David Hein, M.S., is a Data Scientist in the Lyda Hill Department of Bioinformatics at UT Southwestern.

“Constructing highly detailed, accurate datasets from free-text medical records is extremely time-consuming, often requiring extensive manual chart review,” said study first author David Hein, M.S., Data Scientist in the Lyda Hill Department of Bioinformatics at UT Southwestern. “Our study demonstrates one approach for creating AI-powered large language models (LLMs) that simplify the process of collecting and organizing medical data for analysis. By automating both data extraction and standardization through AI, we can make large-scale clinical research more efficient.”

To develop the pipeline, researchers used an AI-powered LLM to analyze over 2,200 kidney cancer pathology reports to evaluate the model’s ability to recognize and categorize distinct types of tumors. Through close collaboration with AI scientists, pathologists, clinicians, and statisticians, they refined the workflow through multiple rounds of testing, improving its handling of complex, nuanced information. Their findings were validated against existing electronic medical record (EMR) data to ensure reliability.

Payal Kapur, M.D., is Professor of Pathology and Urology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. She holds the Jan and Bob Pickens Distinguished Professorship in Medical Science, in Memory of Jerry Knight Rymer and Annette Brannon Rymer and Mr. and Mrs. W.L. Pickens.

The results were striking – 99% accuracy in identifying tumor types and 97% accuracy in detecting whether the cancer had metastasized.

“The biggest challenge in training AI to extract data from narrative reports is that clinicians use a wide range of open-ended terms to describe the same finding,” said study co-leader Payal Kapur, M.D., Professor of Pathology and Urology. “It’s not as simple as counting ‘yes-no’ results. Every report contains hundreds of details in narrative form. But with proper input and oversight, an AI model can efficiently review and categorize vast amounts of records with speed and accuracy.”

A final step included testing across a broader dataset of more than 3,500 internal kidney cancer pathology reports with similar results – a process facilitated by the high-quality, curated data and pipelines available through UT Southwestern’s Kidney Cancer Program.

“The key is collaborative teamwork across specialties to refine AI instructions and ensure accuracy,” said study co-author James Brugarolas, M.D., Ph.D., Director of the Kidney Cancer Program, Professor of Internal Medicine in the Division of Hematology and Oncology, and member of the Cellular Networks in Cancer Research Program of the Harold C. Simmons Comprehensive Cancer Center. 

James Brugarolas, M.D., Ph.D., is Director of the Kidney Cancer Program, Professor of Internal Medicine in the Division of Hematology and Oncology, and member of the Cellular Networks in Cancer Research Program of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D.

While this study focused on kidney cancer, the approach may have broader applications to other tumor types, the authors said. 

“There is no ‘one-size-fits-all’ model for medical data extraction,” said study co-leader Andrew Jamieson, Ph.D., Assistant Professor and Principal Investigator in the Lyda Hill Department of Bioinformatics. “But our study outlines key strategies that can help other researchers use AI-powered LLMs more effectively in their own specialties. We’re excited to continue refining this process and expanding AI’s role in medical research.”

Other UTSW researchers who contributed to the study are Bingqing Xie, Ph.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology and Kidney Cancer Program; Joseph Vento, M.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology; Lindsay Cowell, Ph.D., Professor, Peter O’Donnell Jr. School of Public Health and Department of Immunology; Scott Christley, Ph.D., Computational Biologist, O’Donnell School of Public Health; Ameer Hamza Shakur, Ph.D., Data Scientist/Machine Learning Engineer, Lyda Hill Department of Bioinformatics; Michael Holcomb, M.S., Lead Data Scientist, Lyda Hill Department of Bioinformatics; Alana Christie, M.S., Biostatistical Consultant, Simmons Cancer Center and Kidney Cancer Program; Neil Rakheja, student intern, Simmons Cancer Center; and AJ Jain, Ph.D. candidate, Biomedical Engineering.

Andrew Jamieson, Ph.D., is Assistant Professor and Principal Investigator in the Lyda Hill Department of Bioinformatics at UT Southwestern.

Dr. Kapur holds the Jan and Bob Pickens Distinguished Professorship in Medical Science, in Memory of Jerry Knight Rymer and Annette Brannon Rymer and Mr. and Mrs. W.L. Pickens.

Dr. Brugarolas holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D.

Drs. Kapur, Brugarolas, and Cowell are members of the Simmons Cancer Center. 

The study was funded by a grant from the National Cancer Institute’s Kidney Cancer Specialized Program of Research Excellence (P50 CA196516) and an endowment from the Brock Fund for Medical Science Chair in Pathology.

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – July 24, 2025 – Researchers at UT Southwestern Medical Center have discovered how a hormone interacts with a receptor on the surface of immune cells to shield cancer cells from the body’s natural defenses. The findings, published in Nature Immunology, could lead to new immunotherapy approaches for treating cancer as well as potential treatments for inflammatory disorders and neurologic diseases.

Cheng Cheng “Alec” Zhang, Ph.D., is Professor of Physiology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He holds the Hortense L. and Morton H. Sanger Professorship in Oncology and is a Michael L. Rosenberg Scholar in Medical Research.

“Myeloid cells are among the first group of immune cells recruited to tumors, but very quickly these tumor-fighting cells turn into tumor-supporting cells. Our study suggests that receptors on these myeloid cells get stimulated by this hormone and end up suppressing the immune system,” said Cheng Cheng “Alec” Zhang, Ph.D., Professor of Physiology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Zhang co-led the study with first author Xing Yang, Ph.D., a postdoctoral researcher in the Zhang Lab.

Current immunotherapies, such as immune checkpoint inhibitors, are effective for only about 20%-30% of cancer patients, Dr. Zhang said, suggesting that there are multiple ways that cancers evade attack from the immune system.

Several years ago, researchers in the Zhang Lab studying cancer-fighting immune cells called myeloid cells identified an inhibitory receptor called LILRB4. Stimulating this receptor blocked the myeloid cells’ ability to attack tumors.

Dr. Zhang, Dr. Yang, and their colleagues then did a genome-wide screen of all proteins that might interact with LILRB4. A promising hit was a hormone called SCG2. Although researchers have suggested that SCG2 plays a role in immune response, its function and receptor were unknown. Laboratory experiments confirmed that SCG2 binds to LILRB4, kicking off a signaling cascade that turned off the cancer-fighting abilities of myeloid cells and inhibited their ability to recruit cancer-fighting T cells to tumors.

In mice genetically altered to express the human form of LILRB4, injected cancer cells that produced SCG2 grew rapidly as tumors. Treating these mice with an antibody that blocks LILRB4 significantly slowed cancer growth, as did artificially ridding the animals’ bodies of SCG2.

Together, these experiments suggest that interactions between LILRB4 and SCG2 allow cancer to grow unchecked by myeloid cells, T cells, and potentially other immune cell types. Dr. Zhang suggested that disrupting this interaction could someday offer a new immunotherapy option to treat cancer. Conversely, because this interaction neutralizes myeloid cells’ immune activity, delivering extra SCG2 could be a promising treatment for autoimmune or inflammatory disorders spurred by myeloid cells. Dr. Zhang and his colleagues plan to investigate both ideas in future studies.

Other UTSW researchers who contributed to this study include Xuewu Zhang, Ph.D., Professor of Pharmacology and Biophysics; Cheryl Lewis, Ph.D., Associate Professor in the Simmons Cancer Center and of Pathology; Lin Xu, Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health and of Pediatrics; Jingjing Xie, Ph.D., Instructor of Physiology; Qi Lou, Ph.D., Assistant Instructor of Physiology; Lei Guo, Ph.D., Computational Biologist; and Meng Fang, Ph.D., Chengcheng Zhang, Ph.D., Ankit Gupta, Ph.D., and Lianqi Chen, Ph.D., postdoctoral researchers.

Dr. Alec Zhang holds the Hortense L. and Morton H. Sanger Professorship in Oncology and is a Michael L. Rosenberg Scholar in Medical Research. Dr. Xuewu Zhang and Dr. Xu are members of the Simmons Cancer Center.

This study was funded by grants from the National Cancer Institute (NCI) (R01CA248736, R01CA263079, and Lung Cancer 779 SPORE Development Research Program), the Cancer Prevention and Research Institute of Texas (RP220032, RP15150551, RP190561), The Welch Foundation (AU-0042-20030616, I-1702), Immune-Onc Therapeutics Inc. (Sponsored Research Grant No. 111077), the National Institutes of Health (R35GM130289), and NCI Cancer Center Support Grant (P30CA142543).

The University of Texas has a financial interest in Immune-Onc in the form of equity and licensing. Dr. Alec Zhang holds equity in and had sponsored research agreements with Immune-Onc.

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

Shorter hospital stays safe for most children with anaphylaxis

Up to 5% of the U.S. population has experienced anaphylaxis – a severe allergic reaction triggered by foods, medications, insect stings, or other causes. Children with this reaction typically receive care in a hospital emergency department (ED), where they’re treated with an injection of epinephrine and kept for observation in case they need a second shot or further treatment. But how long children should remain before safely leaving the hospital has been unclear.

A team of researchers including UT Southwestern Medical Center Pediatrics faculty members Jo-Ann Nesiama, M.D., Professor, and Geetanjali Srivastava, M.D., M.P.H., Associate Professor, collected data on 5,641 ED visits for pediatric anaphylaxis between 2016 and 2019 from 30 hospitals in the U.S. (including Children’s Health) and one in Canada. Their findings, reported in The Lancet Child & Adolescent Health, showed that 95% could safely leave the ED after two hours, and 98% could safely go home four hours after one epinephrine dose, with the longer observation sometimes necessary for children with cardiovascular symptoms.

These results suggest the vast majority of children with anaphylaxis don’t need lengthy hospital stays, the authors say.

Reducing LDL cholesterol with experimental drug

To decrease heart attacks, strokes, and other cardiovascular events, patients with prior heart disease and those at increased risk are recommended statins and other medications to reduce low-density lipoprotein cholesterol (LDL-C). Many patients taking these medications are unable to reach their treatment goals. The experimental drug obicetrapib is a new class of cholesterol-lowering medication that has shown promise in reducing LDL-C on top of other cholesterol-reducing therapies. However, its safety and efficacy had not been fully assessed.

In a phase three clinical trial published in the The New England Journal of Medicine, 1,686 participants considered at high risk of a cardiovascular event were randomized to receive obicetrapib in addition to cholesterol-lowering drugs they were taking, and 844 other participants were randomly assigned to receive a placebo. After 84 days, those who received the study drug experienced an average decrease in LDL of almost 30%, while those who received the placebo experienced a nearly 3% rise. Side effects were comparable between the groups. Another ongoing clinical trial, PREVAIL, is underway to determine if the medication will prevent heart attacks and strokes.

Ann Marie Navar, M.D., Ph.D., Associate Professor of Internal Medicine and Public Health at UT Southwestern, served on the steering committee for the study and is a co-author on the manuscript. She received personal compensation from Amgen.

Clinical trial supports new treatment for urothelial carcinoma

Urothelial carcinoma, a cancer that originates from cells lining the bladder and other parts of the urinary system, kills nearly 200,000 worldwide each year. A phase three clinical trial showed that a combination of two treatments, enfortumab vedotin (an antibody-drug conjugate) plus pembrolizumab (an immune checkpoint inhibitor), safely extended both progression-free survival (a measure of how long patients live without their cancer worsening) as well as overall survival in patients with this disease. However, these results included only about 1.5 years of data.

A multicenter team of researchers, including Waddah Arafat, M.D., Associate Professor of Internal Medicine at UT Southwestern, recently published new results in Annals of Oncology from the same trial following patients for about 2.5 years. Their findings showed the combined therapy nearly doubled median progression-free survival and more than doubled median overall survival in the 442 patients on this regimen compared with 444 who received chemotherapy instead. These positive results, along with new data confirming the regimen’s safety, reinforce this treatment as the new gold standard for urothelial carcinoma, the study’s authors say.

UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center played a key role in the trial as the No. 2 enrolling site in the U.S. and No. 5 globally. This effort reflects UTSW’s commitment to advancing science and giving patients access to promising and cutting-edge therapies. The trial included patients from Simmons Cancer Center regional locations in the greater Dallas-Fort Worth area, led by Suzanne Cole, M.D., Associate Professor of Internal Medicine.

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – July 03, 2025 – By using a genetic technique developed at UT Southwestern Medical Center that forces cells to rid themselves of mitochondria, researchers are gaining new insights into the function of these critical organelles. Their findings, published in Cell, add to fundamental knowledge about the role of mitochondria in cells and evolution and could eventually lead to new treatments for patients with mitochondrial diseases such as Leigh syndrome and Kearns-Sayre syndrome, which can affect numerous organ systems.

Jun Wu, Ph.D., is Associate Professor of Molecular Biology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He is a Virginia Murchison Linthicum Scholar in Medical Research.

“Our new tool allows us to study how changes in mitochondrial abundance and the mitochondrial genome affect cells and organisms,” said Jun Wu, Ph.D., Associate Professor of Molecular Biology at UT Southwestern. Dr. Wu co-led the study with Daniel Schmitz, Ph.D., a former graduate student in the Wu Lab who is now a postdoctoral fellow at the University of California, Berkeley.

Mitochondria are organelles found in the cells of most eukaryotic organisms, including animals, plants, and fungi, whose cells contain a membrane-bound nucleus and other membrane-bound organelles. They have their own genetic material, passed down exclusively through females of a species. Mitochondria are thought to have originated as prokaryotic cells – which lack membrane-bound organelles – and to have invaded ancestral eukaryotic cells and formed a symbiotic relationship with them.

Researchers have long known that these organelles serve as cells’ powerhouses, generating the energetic molecule adenosine triphosphate that fuels all cellular operations. However, recent studies have shown mitochondria play direct roles in regulating cell death, differentiating stem cells into other cell types, transmitting molecular signals, aging, and developmental timing.

Although mitochondria appear to perform many of these roles through “crosstalk” with the DNA in a cell’s nucleus, how they perform this function – and what happens if this crosstalk ceases – has been unknown.

Daniel Schmitz, Ph.D., is a former graduate student in the Wu Lab at UT Southwestern.

To help answer these questions, Dr. Wu, Dr. Schmitz, and their colleagues took advantage of a pathway called mitophagy that cells normally use to dispose of old or damaged mitochondria. Using genetic engineering, the researchers forced cells to degrade all their mitochondria – a process known as “enforced mitophagy.”

The researchers used this process on human pluripotent stem cells (hPSCs), a type of cell typically formed early in development that can differentiate into other cell types. Although this alteration caused the cells to stop dividing, the researchers unexpectedly found that the mitochondria-depleted cells could survive in petri dishes up to five days. They had similar results with different types of mouse stem cells and hPSCs harboring a pathogenic mitochondrial DNA mutation, suggesting enforced mitophagy can be a viable tool for depleting mitochondria across species and cell types.

To determine how removing mitochondria affected the hPSCs, the researchers assessed nuclear gene expression. They found that 788 genes became less active and 1,696 became more active. An analysis of the affected genes showed the hPSCs appeared to retain their ability to form other cell types and that they could partially compensate for the lack of mitochondria, with proteins encoded by nuclear genes taking over energy production and certain other functions typically performed by the missing organelles.

Then the researchers, in an attempt to better understand crosstalk between mitochondria and the cell nucleus, fused hPSCs with pluripotent stem cells (PSCs) from humans’ closest primate relatives – including chimpanzee, bonobo, gorilla, and orangutan. This formed “composite” cells with two nuclear genomes and two sets of mitochondria, one from each species. These composite cells selectively removed all non-human primate mitochondria, leaving behind only human mitochondria.

Next, using enforced mitophagy, the scientists created hPSCs devoid of human mitochondria and fused them to non-human primate PSCs, again creating cells carrying nuclear genomes from both species, but this time only non-human mitochondria. An analysis of composite cells containing either human or non-human mitochondria showed that the mitochondria were largely interchangeable despite millions of years of evolutionary separation, causing only subtle differences in gene expression within the composite nucleus.

Interestingly, the genes that differed in activity among cells harboring human and non-human mitochondria were mostly linked to brain development or neurological diseases. This raises the possibility that mitochondria may play a role in the brain differences between humans and our closest primate relatives. However, Dr. Wu said, more research – especially studies comparing neurons made from these composite PSCs – will be needed to better understand these differences.

Finally, the researchers studied how depleting mitochondria might affect development in whole organisms. They used a genetically encoded version of enforced mitophagy to reduce the amount of mitochondria in mouse embryos, then implanted them into surrogate mothers to develop. Embryos missing more than 65% of their mitochondria failed to implant in their surrogate’s uterus. However, those missing about a third of their mitochondria experienced delayed development, catching up to normal mitochondrial numbers and a typical developmental timeline by 12.5 days after fertilization.

Together, the researchers say, these results serve as starting points for new lines of research into the different roles mitochondria play in cellular function, tissues and organ development, aging, and species evolution. They plan to use enforced mitophagy to continue studying these organelles in a variety of capacities.

Other UTSW researchers who contributed to this study are Peter Ly, Ph.D., Assistant Professor of Pathology and Cell Biology; Daiji Okamura, Ph.D., Visiting Assistant Professor of Molecular Biology; Seiya Oura, Ph.D., and Leijie Li, Ph.D., postdoctoral researchers; Yi Ding, Ph.D., Research Associate; Rashmi Dahiya, Ph.D., Senior Research Associate; Emily Ballard, B.S., graduate student researcher; and Masahiro Sakurai, Ph.D., Research Scientist.

Dr. Wu is a Virginia Murchison Linthicum Scholar in Medical Research. Drs. Wu and Ly are members of the Harold C. Simmons Comprehensive Cancer Center.

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – July 02, 2025 – Adding targeted radiation to chemotherapy prior to surgery may offer better control of pancreatic tumors – potentially reducing the rate of recurrence after treatment, according to a new study from UT Southwestern Medical Center. Published in Clinical Cancer Research, the novel study offers evidence of a more effective approach with biological insights for treating one of the most aggressive and lethal forms of cancer.

Todd Aguilera, M.D., Ph.D., is Assistant Professor of Radiation Oncology and a member of the Experimental Therapeutics Research Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“Pancreatic ductal adenocarcinoma (PDAC) is extremely difficult to treat because even after chemotherapy and surgery, tumors often grow back, many times at the original site,” said study leader Todd Aguilera, M.D., Ph.D., Assistant Professor of Radiation Oncology and a member of the Experimental Therapeutics Research Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “Our findings suggest stereotactic ablative radiotherapy (SAbR), which delivers high-dose radiation with minimal toxicity, may improve clinical outcomes for patients with PDAC by lowering the risk of recurrence – especially in cancers that invade or encase major arteries.”

The retrospective study compared 181 patients who were treated for pancreatic cancer at UT Southwestern and Parkland Health between 2012 and 2023 using neoadjuvant chemotherapy – designed to shrink the tumor prior to surgery – and either received or didn’t receive SAbR. Using RNA sequencing, the researchers examined molecular changes in tumor tissue among 43 of those patients to understand the biological effects of SAbR. 

Despite having more advanced disease at the outset, patients treated with SAbR had better treatment response and notably improved local control, or prevention of recurrence at the original site – particularly when arterial involvement was present — but similar overall survival rates. “This matters because local tumor regrowth causes significant suffering for patients,” Dr. Aguilera said. “As systemic therapies continue to improve, the burden of local recurrence becomes even more prominent – and more important to address.” 

The researchers, including first author and M.D./Ph.D. student researcher Peter Q. Leung, also found evidence that SAbR stimulated the immune system, increasing cancer-fighting lymphocytes in SAbR-treated tumors.

UT Southwestern M.D./Ph.D. student researcher Peter Q. Leung is the study's first author.

“While further study is needed, it’s possible that there is potential in combining high-dose ablative radiation with immunotherapies,” Dr. Aguilera said. “That could open up new areas to enhance antitumor immunity and ultimately improve cure rates for pancreatic patients, which today stand only at around 30% for those who undergo surgery.”

The research builds upon previous studies conducted in the Aguilera Lab, which focus on understanding how radiation changes the tumor microenvironment. 

“With high-resolution tools like single-cell RNA sequencing and multiplexed immunofluorescence, we are now investigating how each patient’s tumor responds at the cellular and molecular level and using that insight to develop smarter, more targeted treatments,” Dr. Aguilera said. “Detailed tissue analyses like those conducted here at UT Southwestern are critical for uncovering new therapeutic directions. This kind of work is only possible at a center like ours, where an interdisciplinary team collaborates closely to tailor the right treatment path for each patient. It also depends on the incredible commitment of our patients, who empower us to learn from every case. And none of it happens without dedicated trainees like Mr. Leung and the rest of our team, who take on critical parts of the effort.”

Dr. Aguilera is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research, a National Cancer Institute (NCI) Cancer Moonshot Scholar, and a Damon Runyon Clinical Investigator.  

Other UTSW researchers who contributed to the study are Herbert J. Zeh III, M.D., Chair and Professor of Surgery; Adam C. Yopp, M.D., Professor of Surgery and Chief of the Division of Surgical Oncology; John C. Mansour, M.D., Professor of Surgery; Song Zhang, Ph.D., Professor in the Peter O’Donnell Jr. School of Public Health; Cheryl M. Lewis, Ph.D., Associate Professor in the Simmons Cancer Center and of Pathology; Patricio M. Polanco, M.D., Associate Professor of Surgery, Director of Robotic Surgery Training, co-Director of the Pancreatic Cancer Program, and co-Director of the Pancreatic Cancer Prevention Clinic; Nina N. Sanford, M.D., Associate Professor of Radiation Oncology and Chief of Gastrointestinal Radiation Oncology Service; Syed Kazmi, M.D., Associate Professor of Internal Medicine in the Division of Hematology and Oncology; Matthew R. Porembka, M.D., Associate Professor of Surgery; Megan Wachsmann, M.D., Assistant Professor of Pathology; Zhikai Chi, M.D., Ph.D., Assistant Professor of Pathology; Salwan Al Mutar, M.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology; David Hsieh, M.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology; Eslam A. Elghonaimy, Ph.D., Instructor of Radiation Oncology; Muhammad S. Beg, M.D., Adjunct Associate Professor of Internal Medicine in the Division of Hematology and Oncology; Ahmed M. Elamir, M.D., Clinical Fellow in Radiation Oncology; Neha Barrows, B.S., Research Assistant II in Radiation Oncology; Hollis Notgrass, M.S., Lead Pathologist Assistant; Ethan Johnson, Clinical Research Coordinator; Cassandra Hamilton, B.S., Senior Regulatory Analyst; and Samy Castillo-Flores, M.D., and Ricardo E. Nunez Rocha, M.D., postdoctoral researchers.

Drs. Zeh, Yopp, Mansour, Zhang, Lewis, Polanco, Sanford, Kazmi, Porembka, Wachsmann, Chi, Al Mutar, and Hsieh are all members of Simmons Cancer Center.   

The study was funded by a Simmons Cancer Center Translational Cancer Research Pilot Grant; CPRIT (RR170051); the Carroll Shelby Foundation; the UT Southwestern Disease Oriented Scholars Program; and an NCI Cancer Center Support Grant (P30CA142543).

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

About Parkland Health

Parkland Health is one of the largest public hospital systems in the country. Premier services at the state-of-the-art Parkland Memorial Hospital include the Level I Rees-Jones Trauma Center, the only burn center in North Texas verified by the American Burn Association for adult and pediatric patients, and a Level III Neonatal Intensive Care Unit. The system also includes two on-campus outpatient clinics – the Ron J. Anderson, MD Clinic and the Moody Outpatient Center, as well as more than 30 community-based clinics and numerous outreach and education programs. By cultivating its diversity, inclusion, and health equity efforts, Parkland enriches the health and wellness of the communities it serves. For more information, visit parklandhealth.org.

DALLAS – June 23, 2025 – Using gene editing in a preclinical model, researchers at UT Southwestern Medical Center blocked the symptoms of a rare smooth muscle disease before they developed. Their findings, published in Circulation, could eventually lead to gene therapies for this and other genetic diseases affecting smooth muscle cells.

Eric Olson, Ph.D., is Chair and Professor of Molecular Biology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Olson holds The Robert A. Welch Distinguished Chair in Science, the Pogue Distinguished Chair in Research on Cardiac Birth Defects, and the Annie and Willie Nelson Professorship in Stem Cell Research.

“Gene editing has been used in other disease contexts, but its application to inherited vascular diseases, particularly targeting smooth muscle cells in vivo, is still emerging. Our approach advances the field by demonstrating functional correction in a cell type that’s notoriously difficult to target,” said Eric Olson, Ph.D., Chair and Professor of Molecular Biology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Olson co-led the study with Ning Liu, Ph.D., Professor of Molecular Biology, and first author Qianqian Ding, Ph.D., postdoctoral researcher, both members of the Olson Lab.

Fewer than 1,000 people in the U.S. have multisystem smooth muscle dysfunction syndrome (MSMDS). This disease is marked by widespread disorders in smooth muscles, a type of non-striated contractile tissue found in blood vessels and various hollow organs.

Patients with MSMDS develop problems affecting the lungs, gastrointestinal system, kidneys, bladder, and eyes beginning in childhood. They are also significantly more vulnerable to aortic aneurysms and aortic dissections – medical emergencies affecting the body’s largest artery that necessitate emergency surgery to prevent sudden death.

Because MSMDS is often caused by a single nucleotide mutation – a pathological change in one “letter” of the genetic code, in this case in a gene called ACTA2 – gene therapy could theoretically cure patients with this disease, Dr. Ding explained. However, no gene therapies developed thus far have successfully targeted smooth muscle tissues.

Ning Liu, Ph.D., is Professor of Molecular Biology at UT Southwestern.

To look for a possible solution, Drs. Ding, Liu, and Olson and their colleagues used a strategy called base editing – a variation of the CRISPR gene editing method that uses targeted molecular machinery to swap one specific letter of the genetic code for another, converting a mutant gene to its healthy form. The researchers tested this approach first in human smooth muscle cells carrying mutant ACTA2. After introducing the base editing components into mutant cells growing in petri dishes, the scientists showed that the disease-causing mutant version of ACTA2 was corrected. This treatment resolved pathological traits seen in the mutant cells, including an inability to contract and excessive proliferation and migration.

While this gene editing strategy appeared to be successful in cells, Dr. Ding explained, applying it in whole organisms was far more challenging because the base editing machinery must be expressed specifically in smooth muscle cells. To achieve this, they packaged them with a promoter – a DNA fragment that ensures genes are expressed in the right cell type. Mice carrying the human ACTA2 mutation responsible for MSMDS that received the base editing components three days after birth remained healthy, while untreated mice developed symptoms including enlarged bladders and kidneys, dilated small intestines, and weakened aortas.

This strategy might be effective in human patients early in their disease process – an approach the team hopes will eventually be tested in clinical trials. They plan to investigate in future studies whether gene editing could reverse symptoms of MSMDS after they’ve developed and whether their approach could hold promise for other genetic smooth muscle diseases.

First author Qianqian Ding, Ph.D., is a postdoctoral researcher in the Olson Lab at UT Southwestern.

Other UTSW researchers who contributed to this study are Lin Xu, Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health and of Pediatrics; Hui Li, Ph.D., and John McAnally, B.S., Senior Research Scientists; Lei Guo, Ph.D., Computational Biologist; Camryn MacDonald, B.S.A., Research Assistant; Wei Tan, M.D., and Efrain Sanchez-Ortiz, Ph.D., Research Scientists; and Peiheng Gan, Ph.D., M.B.B.S., and Zhisheng Xu, Ph.D., postdoctoral researchers.

Dr. Olson, Director of the Hamon Center for Regenerative Science and Medicine, holds The Robert A. Welch Distinguished Chair in Science, the Pogue Distinguished Chair in Research on Cardiac Birth Defects, and the Annie and Willie Nelson Professorship in Stem Cell Research.

This study was funded by grants from the National Institutes of Health (R01HL130253, R01HL157281, P50HD087351), The Welch Foundation (1-0025), The Leducq Foundation Transatlantic Networks of Excellence, the British Heart Foundation’s Big Beat Challenge award to CureHeart (BBC/F/21/220106), and the American Heart Association (25POST1372779).

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – June 18, 2025 – A gene-editing delivery system developed by UT Southwestern Medical Center researchers simultaneously targeted the liver and lungs of a preclinical model of a rare genetic disease known as alpha-1 antitrypsin deficiency (AATD), significantly improving symptoms for months after a single treatment, a new study shows. The findings, published in Nature Biotechnology, could lead to new therapies for a variety of genetic diseases that affect multiple organs.

Daniel Siegwart, Ph.D., is Professor of Biomedical Engineering, Biochemistry, and in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He holds the W. Ray Wallace Distinguished Chair in Molecular Oncology Research.

“Multi-organ diseases may need to be treated in more than one place. The development of multi-organ-targeted therapeutics opens the door to realizing those opportunities for this and other diseases,” said study leader Daniel Siegwart, Ph.D., Professor of Biomedical Engineering, Biochemistry, and in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Gene editing – a group of technologies designed to correct disease-causing mutations in the genome – has the potential to revolutionize medicine, Dr. Siegwart explained. Targeting these technologies to specific organs, tissues, or cell populations will be necessary to effectively and safely treat patients.

In 2020, the Siegwart Lab reported a new approach called Selective Organ Targeting, or SORT, which uses specific components in the lipid nanoparticles (LNPs) that encapsulate gene-editing molecules to target certain organs. Although the researchers have demonstrated that SORT can edit genes selectively in specific organs, such as the liver, lungs, and spleen, the team had yet to demonstrate that this system could target multiple organs simultaneously.

Genetic therapies aimed at more than one organ will be critical to treat diseases like AATD, in which a mutation that affects a single nucleotide – one “letter” in the genetic code – causes buildup of a toxic protein in the liver. Because the healthy version of this protein also plays a role in inhibiting an enzyme that breaks down a key protein in the lungs, AATD patients’ lungs are also affected, leading to a form of emphysema.

To correct the causative mutation in both organs simultaneously, Dr. Siegwart and his colleagues re-engineered the SORT nanoparticles to carry large gene-editing proteins necessary to replace the single affected nucleotide with a healthy one. They also developed new formulas for the liver- and lung-targeting nanoparticles, changing their ingredients to more efficiently reach these organs.

Tests in liver cells derived from patients showed these new nanoparticles effectively edited the mutated gene, known as SERPINA1. In a mouse model of AATD that carries the mutated human gene in each cell, a single dose of the liver- and lung-targeting SORT nanoparticles resulted in gene editing of about 40% of liver cells and about 10% of AT2 lung cells – those primarily affected by AATD. Evaluation of liver cells showed that editing remained stable in this organ for at least 32 weeks, reducing levels of the mutated protein by 80%.

Within four weeks of this treatment, aggregates of the toxic protein in the liver had faded away. Although this mouse model doesn’t develop the same lung pathology as human patients, the researchers found that the damaging lung enzyme left unchecked in AATD was inhibited by 89%.

Together, Dr. Siegwart said, these results show that SORT can be used to treat multi-organ diseases. He and his colleagues continue to develop SORT into clinical therapies for various diseases through ReCode Therapeutics, which has licensed intellectual property from UT Southwestern. Dr. Siegwart is a co-founder and member of the scientific advisory board of the company. He has financial interests in ReCode Therapeutics, Signify Bio, and Jumble Therapeutics.

Other UTSW researchers who contributed to this study are first author Minjeong Kim, Ph.D., postdoctoral researcher; Sumanta Chatterjee, Ph.D., Instructor of Biomedical Engineering; Eunice S. Song, B.S., Yehui Sun, M.S., and Shiying Wu, B.S., graduate student researchers; Sang M. Lee, Ph.D., postdoctoral researcher; Priyanka Patel, M.Sc., Research Associate; and Zeru Tian, Ph.D., Research Scientist.

Dr. Siegwart holds the W. Ray Wallace Distinguished Chair in Molecular Oncology Research.

This study was funded by a Sponsored Research Agreement with ReCode Therapeutics and a grant from the National Institutes of Health National Institute of Biomedical Imaging and Bioengineering (R01 EB025192-01A1).

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

Nagesh Peddada, Ph.D., is Assistant Professor in the Center for the Genetics of Host Defense and of Immunology at UT Southwestern.

“Seeing the structure of midnolin lends insight on how this protein helps cells dispose of other unneeded proteins in a way that’s different from the classical mechanism we’re used to seeing – a process that could have significant implications for cancer and immune-related diseases,” said Nagesh Peddada, Ph.D., Assistant Professor in the Center for the Genetics of Host Defense and of Immunology at UT Southwestern. He co-led the study with Bruce Beutler, M.D., Director of the Center for the Genetics of Host Defense and Professor of Immunology and Internal Medicine.

Dr. Beutler, who shared the 2011 Nobel Prize in Physiology or Medicine for his discovery of an important family of receptors found on immune cells, has long used mutagenesis – a method for introducing mutations into the genes of animal models – as a key approach for discovering the function of genes. Recently, the Beutler Lab pioneered a method known as automated meiotic mapping (AMM) that links abnormal traits in mutant mice to the mutations that cause them, thereby identifying genes needed to maintain a normal physiologic state.

Bruce Beutler, M.D., is Director of the Center for the Genetics of Host Defense and Professor of Immunology and Internal Medicine at UT Southwestern. Dr. Beutler, a Nobel Laureate and a Regental Professor, holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr. He is also a member of the Harold C. Simmons Comprehensive Cancer Center.

Combining these tools, he and his colleagues reported last year that mutations in Midn, the gene that produces midnolin, protected mice genetically predisposed to developing B-cell leukemias and lymphomas. B cells, which are critical components of the adaptive immune system, divide out of control in these types of cancer. Using genetic tricks to eliminate or drastically reduce midnolin production significantly extended the affected animals’ lifespans by preventing them from developing these diseases at all.

Further experiments revealed that midnolin’s role in B cells is to ferry proteins to proteasomes, cellular organelles that degrade proteins that are damaged or no longer useful to the cell. Midnolin also stimulates proteasome activity, increasing the rate at which damaged proteins are removed from cells. Nearly all proteins routed to proteasomes are tagged for disposal by another protein called ubiquitin. However, proteins carried by midnolin aren’t tagged with ubiquitin, Dr. Peddada explained. How midnolin functions without ubiquitin’s help has been unclear.

Using UTSW’s Cryo-Electron Microscopy Facility, the researchers obtained three-dimensional images of midnolin bound to proteasomes at nearly atomic-level resolution. These images revealed key portions of midnolin that are critical for its partnership with proteasomes. One of these portions has a shape similar to ubiquitin that allows midnolin to open the same gateway in proteasomes that proteins must cross for their disposal.

Some therapies for B-cell leukemias and lymphomas work by inhibiting proteasome activity, Dr. Beutler explained. However, proteasome inhibitors come with a host of side effects, including gastrointestinal problems, decreased platelets that pose a bleeding risk, and nerve damage. Because midnolin is found primarily in B cells, developing drugs that block any of its actions could offer a safer alternative to proteasome inhibitors – a topic that the Beutler Lab plans to investigate in the future.

This image shows the structure of a 26S proteasome (in tan and grey). A protein called midnolin (red) helps deliver unwanted proteins to the proteasome and connects with two key parts — RPN1 (blue) and RPN11 (green). This setup helps guide the unwanted protein to the right spot so the proteasome can break it down and keep the cell healthy.

Other UTSW researchers who contributed to this study include Xiaochen Bai, Ph.D., Associate Professor of Biophysics and Cell Biology; Xue Zhong, Ph.D., Jin Huk Choi, Ph.D., and Eva Maria Y. Moresco, Ph.D., Assistant Professors in the Center for the Genetics of Host Defense and of Immunology; Yan Yin, Ph.D., Research Scientist; Danielle Renee Lazaro, B.S., Research Technician II; Jianhui Wang, M.S., Senior Research Scientist; and Stephen Lyon, M.A., Computational Research Scientist.

Dr. Beutler, a Regental Professor, holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr. He is also a member of the Cellular Networks in Cancer Research Program in the Harold C. Simmons Comprehensive Cancer Center at UTSW.

This research was funded by grants from the National Institutes of Health (R01AI125581) and The Welch Foundation (I-1944).

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – June 04, 2025 – A genetic mutation that fuses two genes drives several different cancer types by forming networks of protein interactions that alter gene expression in cells, a study by UT Southwestern Medical Center researchers suggests. The findings, published in Cell, could lead to new treatments for an aggressive kidney cancer and may hold promise for a diverse set of other cancers, the study authors said.

“This research identifies a common molecular mechanism shared across diverse cancer-driving oncofusions, revealing a potentially druggable vulnerability,” said Benjamin Sabari, Ph.D., Assistant Professor in the Cecil H. and Ida Green Center for Reproductive Biology Sciences and member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Sabari co-led the study with first authors Heankel Lyons, Ph.D., a former member of the Sabari Lab who is now a postdoctoral researcher at Stanford University, and Prashant Pradhan, Ph.D., a postdoctoral researcher at UTSW.

Benjamin Sabari, Ph.D., is Assistant Professor in the Cecil H. and Ida Green Center for Reproductive Biology Sciences and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Mutations involving fusions of genes, known as chromosomal translocations, are relatively common in cancers; the different hybrid proteins that they produce, known as oncofusions, are thought to play roles in about 17% of malignancies, Dr. Sabari explained. Why fusing different portions of proteins together causes cancer is understood for a few cancers, but it is unclear for others. These include translocation renal cell carcinoma (tRCC), an aggressive cancer subtype that affects about 4% of adults with renal cell carcinoma and is the most common renal cell carcinoma subtype in children.

About two-thirds of tRCC cases are thought to be caused by fusion of the gene that codes for the transcription factor TFE3 (a protein that’s key for activating specific genes) with one of three other genes: PRCC, ASPL, or SFPQ. Because the three genes seemingly have nothing in common, Dr. Sabari said, why TFE3 fuses with these specific partners and how this fusion confers malignancy was unknown.

To answer these questions, Drs. Sabari, Lyons, and Pradhan and their colleagues examined tRCC cells from patients treated in UTSW’s Kidney Cancer Program, kept in a biorepository led by study co-author James Brugarolas, M.D., Ph.D., Professor of Internal Medicine and the program’s Director. Using a special stain, they saw that the oncofusion proteins formed biomolecular condensates – dynamic networks of different proteins that segregate themselves within cells – but the “wild-type” (not mutated) TFE3 protein did not. These results suggest that a common feature of the seemingly random fusion partners is the ability to form condensates.

Previous work from the Sabari Lab has shown that condensates can regulate transcription – the process that copies the genetic information in DNA into RNA, an initial step for producing proteins from genes – by selectively capturing key regulatory proteins at target genes. This finding led the researchers to investigate whether oncofusion condensates selectively captured common proteins. When the researchers mixed material extracted from cell nuclei with oncofusion proteins produced by the TFE3 translocation, the proteins readily formed biomolecular condensates, confirming that these hybrid proteins spur condensate formation. Examining proteins enmeshed in the oncofusion condensates identified RNA polymerase II, an enzyme responsible for transcription.

How these three different oncofusions were all able to capture RNA polymerase II was unclear until the researchers compared the amino acid building blocks that make up normal or wild-type TFE3 with those that make up the three mutated oncofusion versions. They found that the mutated versions contained a higher proportion of amino acids that can chemically interact with RNA polymerase II. Upon swapping amino acids between wild-type TFE3 and the TFE3 oncofusion, the oncofusions lost their ability to interact with RNA polymerase II, whereas, conversely, wild-type TFE3 gained the ability to interact with RNA polymerase II, thus confirming the central role of the identified amino acid mixtures in capturing RNA polymerase II and in driving the process of gene transcription.

Cells carrying wild-type TFE3 engineered to carry more of the amino acids from the mutant version adopted cancerous behaviors, becoming more proliferative, invasive, and migratory. The most likely explanation is that RNA polymerase II bound by the mutant amino acids prompted the expression of genes that cause this malignant activity, said Dr. Sabari, also Assistant Professor of Molecular Biology and Obstetrics and Gynecology.

Curious about whether this mechanism might apply to other cancers, the research team combed through a database of known oncofusion mutations found in a variety of cancer types. By examining the amino acids that these mutations code for, the researchers saw combinations similar to those found in mutated TFE3 and found that these other oncofusions also captured RNA polymerase II. These findings suggest that these other oncofusions might be driving diverse cancers through a similar molecular mechanism observed for tRCC.

Finding a way to disrupt these interactions could offer a new way to treat these cancers – a topic that the Sabari Lab plans to pursue in the future.

Dr. Brugarolas holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D. He is Principal Investigator of the Kidney Cancer SPORE P50CA196516 grant from the National Cancer Institute (NCI).

Other UTSW researchers who contributed to this study are Prasad R. Koduru, Ph.D., Professor of Pathology; Chao Xing, Ph.D., Professor in the Eugene McDermott Center for Human Growth and Development, the Lyda Hill Department of Bioinformatics, and the Peter O’Donnell Jr. School of Public Health; Payal Kapur, M.D., Professor of Pathology and Urology; Gopinath Prakasam, Ph.D., Assistant Instructor of Internal Medicine; Kathleen McGlynn, M.S., Senior Research Associate; Vanina T. Tcheuyap, M.S., Research Associate; Ze Yu, M.S., and Dinesh Ravindra Raju, M.S., Computational Biologists; Shubham Vashishtha, Ph.D., and Xiang Li, Ph.D., postdoctoral researchers; and Mikayla Eppert, B.S., graduate student researcher.

Drs. Brugarolas, Kapur, Koduru, and Xing are members of the Simmons Cancer Center.

The research was funded by grants from the Cancer Prevention and Research Institute of Texas (RR190090), The Welch Foundation (I-2163-20230405 and V-I-0004-20230731), and the National Institutes of Health through the National Institute of General Medical Sciences (GM147583) and the National Cancer Institute through the Kidney Cancer SPORE (P50CA196516) and Cancer Center Support Grant (P30CA142543).

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – May 20, 2025 – Zhijian “James” Chen, Ph.D., Professor of Molecular Biology and Director of the Center for Inflammation Research at UT Southwestern Medical Center, has been elected to the Fellowship of the Royal Society, the United Kingdom’s national academy of sciences and the oldest scientific academy in continuous existence.  

One of the world’s leading experts on innate immunity, Dr. Chen has been recognized with numerous honors for his research, including the 2024 Albert Lasker Basic Medical Research Award and the 2019 Breakthrough Prize in Life Sciences. He has also been elected to both the U.S. National Academy of Sciences and U.S. National Academy of Medicine.

“Dr. Chen’s breakthroughs have significantly advanced the field of immunology, paving the way for new approaches to the development of more effective vaccines and novel therapies for a broad range of diseases, including cancer and autoimmune disorders,” said Daniel K. Podolsky, M.D., President of UT Southwestern. “His election to the Royal Society reflects the vast impact of his discoveries, and UT Southwestern takes great pride in seeing Dr. Chen’s work recognized by this high honor.”

Innate immunity is the body’s first response to pathogens, allowing rapid response when these foreign agents attack and destroy cells and tissues. The Chen Lab is broadly interested in mechanisms of signal transduction – the mechanisms by which cells communicate with their surroundings and detect harmful or foreign insults.

Dr. Chen’s discoveries include the identification of MAVS, the first mitochondrial protein known to be involved in immunity against infections. In 2012, he identified cGAS (cyclic GMP-AMP synthase), which senses foreign DNA in a cell’s interior, or cytoplasm. It then activates STING (stimulator of interferon genes) and triggers an inflammatory response, including the production of type 1 interferons, essential for combating infections and regulating immune responses.

“I am deeply honored and humbled to be elected to the Royal Society. I look forward to the incredible moment when I will have the opportunity to sign the same book that has been signed by Isaac Newton, Charles Darwin, Albert Einstein, and other eminent scientists, including our own Mike Brown and Joe Goldstein. This recognition by the Royal Society reflects the impact of discoveries made through the dedication and talent of the scientists and trainees in my lab, and the potential of our work in improving human health,” said Dr. Chen, who is also a Howard Hughes Medical Institute Investigator and member of the Center for the Genetics of Host Defense and the Harold C. Simmons Comprehensive Cancer Center at UTSW.

Founded in 1660, the Royal Society’s Fellowship includes many of the world’s most eminent scientists, engineers, and technologists. At UT Southwestern, Nobel Laureates Michael S. Brown, M.D., Professor of Molecular Genetics, and Joseph L. Goldstein, M.D., Chair and Professor of Molecular Genetics, are Foreign Members of the Royal Society.

Dr. Chen is also a recipient of the Paul Ehrlich and Ludwig Darmstaedter Prize, Germany’s highest honor in the field of medicine (2025), the Louisa Gross Horwitz Prize (2023), the William B. Coley Award for Distinguished Research in Basic and Tumor Immunology (2020), the Switzer Prize (2019), the Lurie Prize in Biomedical Sciences (2018), and the National Academy of Sciences Award in Molecular Biology (2012).

Dr. Chen holds the George L. MacGregor Distinguished Chair in Biomedical Science. Dr. Podolsky holds the Philip O’Bryan Montgomery, Jr., M.D. Distinguished Presidential Chair in Academic Administration and the Charles Cameron Sprague Distinguished Chair in Biomedical Science. Dr. Brown, a Regental Professor, holds The W.A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research, and the Paul J. Thomas Chair in Medicine. Dr. Goldstein, a Regental Professor, holds the Julie and Louis A. Beecherl, Jr. Distinguished Chair in Biomedical Research, and the Paul J. Thomas Chair in Medicine.

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

FORT WORTH – May 12, 2025 – Ushering in a new era of cancer care in Fort Worth, UT Southwestern Medical Center broke ground today on a $177 million Radiation Oncology campus that will provide the most advanced therapies for patients of the nation’s 12th-largest city.

The 65,000-square-foot facility, which will include the city’s first MRI-guided precision radiation treatment, is expected to meet the growing demands for cancer care in Fort Worth and the surrounding area for decades to come. The campus is projected to open in 2028 and will be connected to UT Southwestern’s Moncrief Cancer Institute in the city’s Medical District.

“This milestone, once completed, will ensure that Tarrant County residents have access to the best available cancer care, combining the latest advances in medical technology with the expertise of our clinicians and researchers, who are some of the top cancer specialists in the country,” said Daniel K. Podolsky, M.D., President of UT Southwestern. 

“Fort Worth is one of the fastest-growing cities in the country, and our high quality of life is a major driver of that growth,” Fort Worth Mayor Mattie Parker said. “To continue to meet this moment, we need world-class health and cancer care. We know UT Southwestern is at the center of that.”

A generous lead gift from esteemed philanthropists Sherri and Robert “Bobby” L. Patton Jr. is helping to make the new expansion possible. Their support underscores the vital role of private philanthropy in advancing UT Southwestern’s impact and ensuring that patients across the region have access to the most cutting-edge radiation oncology services close to home.

“Fort Worth is one of the greatest cities in America. It should have great cancer care. This expansion will bring cutting-edge technology and vital health care to our community,” Sherri Patton said.

As many as two-thirds of cancer patients need radiation therapy, and the UT Southwestern expansion will create the largest radiation oncology facility in the Fort Worth area, broadening access for patients of all oncologists and offering a convenient location close to home for patients living in Fort Worth and the surrounding area, who often require regular or daily trips for this lifesaving treatment.

The new facility will feature:

• Four linear accelerators (LINACs) to deliver precise radiation treatments to patients, with space to add two more LINACs to meet future demand.
• MRI-guided precision radiation treatment – the first of its kind in Fort Worth – to facilitate therapy with unprecedented accuracy.
• Positron emission tomography (PET) imaging, which is critical for accurately diagnosing and evaluating tumor growth.
• A fully equipped brachytherapy suite to provide high-dose radiation treatments for patients with prostate or gynecologic cancers.

UT Southwestern’s cancer program is ranked among the top 25 out of 4,500 hospitals in the nation by U.S. News & World Report, and its Harold C. Simmons Comprehensive Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center in North Texas and one of only 57 in the nation. UTSW also has the largest individual facility for radiation oncology in North Texas, with some of the most sophisticated treatment machines in the world. UTSW’s Department of Radiation Oncology specialists are pioneers in advanced therapies such as stereotactic ablative radiation therapy (SABR) and personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR), which have changed the standard of radiation therapy to make it more targeted and less damaging to healthy tissue.

Moncrief Cancer Institute has been a part of UT Southwestern since 1999, offering screening programs and educational and support services for multiple counties. In 2015, UT Southwestern expanded its cancer care to Fort Worth, offering medical and surgical oncology services, imaging, and chemotherapy.

The new Radiation Oncology campus will join UT Southwestern’s other specialty services provided at the nearby UT Southwestern Monty and Tex Moncrief Medical Center at Fort Worth. This outpatient facility offers primary care and lab services and an on-site retail pharmacy as well as specialty care clinics for cardiology, dermatology, endocrinology and endocrine surgery, neurology and neurosurgery, ophthalmology, otolaryngology (ear-nose-throat), rheumatology, and urology. Expanded imaging services, including 3T MRI, two ultrasound units, CT, and fluoroscopy, were added earlier this year.

Dr. Podolsky holds the Philip O’Bryan Montgomery, Jr., M.D. Distinguished Presidential Chair in Academic Administration and the Charles Cameron Sprague Distinguished Chair in Biomedical Science.

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – May 08, 2025 – A protein identified by researchers at UT Southwestern Medical Center may drive resistance to immune checkpoint inhibitors, a widely used form of immunotherapy to treat cancer. The findings, published in Communications Medicine, link glycoprotein non-metastatic melanoma protein B (GPNMB) to relapse after treatment and suggest it may help tumors evade immune surveillance in metastatic renal cell carcinoma.

“Finding serum GPNMB as a predictor of acquired resistance and a potential target for overcoming that resistance to cancer immunotherapy could contribute to further improvement of the outcome of cancer patients,” said study leader Kiyoshi Ariizumi, Ph.D., Professor of Dermatology at UT Southwestern and a member of the Harold C. Simmons Comprehensive Cancer Center.

Kiyoshi Ariizumi, Ph.D., is Professor of Dermatology at UT Southwestern and a member of the Harold C. Simmons Comprehensive Cancer Center.

Checkpoint inhibitors improve survival for many patients with advanced cancers by removing the molecular “brakes” that prevent immune cells from recognizing and eliminating tumors. However, more than half of patients who initially respond to this type of immunotherapy eventually relapse due to acquired resistance within a few months to years of sustained treatment.

To better understand how this resistance develops, UT Southwestern researchers analyzed tumor and blood samples from 39 patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. Among patients who initially responded positively, 28% developed resistance within two years, coinciding with rising levels of GPNMB in the blood. By comparing samples collected before treatment and after disease progression, the team investigated the molecular changes that may cause relapse.

Using RNA sequencing and whole exome analysis, the researchers found that GPNMB was significantly upregulated in tumors after relapse. Its increase in blood samples during disease progression raises the possibility of its use as a noninvasive biomarker to track treatment response. If validated, such a blood-based marker could help clinicians identify resistance earlier and adjust treatment accordingly.

The team traced the rise in GPNMB to a signaling cascade set in motion by immune checkpoint therapy itself. That same molecular pattern – which also appeared in the blood of relapsing patients – strengthened the connection between the laboratory findings and clinical outcomes.

In mouse models, blocking GPNMB restored CD8+ T cell activity – a critical component of the immune response – and improved the effectiveness of the therapy after it had stopped working. In another experiment, shutting off the gene that produces GPNMB also resensitized resistant tumors to treatment.

“Our findings have great promise in being able to establish personalized cancer medicine specialized for tumor recurrence and create novel inhibitors that restore tumor response to immunotherapy,” Dr. Ariizumi said.

He and other scientists at UTSW have investigated the role of GPNMB in suppressing immune responses to cancer for years. This new work builds on that foundation by directly linking GPNMB to therapy resistance in kidney cancer. Although the study focused on metastatic renal cell carcinoma, the researchers plan to collaborate with clinical oncologists at the Simmons Cancer Center to explore whether GPNMB-driven resistance also plays a role in other cancers treated with immune checkpoint inhibitors.

Other UTSW researchers who contributed to the study are first author Jin-Sung Chung, Ph.D., Instructor of Dermatology; Ponciano Cruz Jr., M.D., Professor of Dermatology; Hans Hammers, M.D., Ph.D., Professor of Internal Medicine in the Division of Hematology and Oncology and co-leader of the Experimental Therapeutics Research Program in the Simmons Cancer Center; Lin Xu, Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health and of Pediatrics; and Lei Guo, Ph.D., Computational Biologist in the Quantitative Biomedical Research Center in the O’Donnell School of Public Health.

Dr. Xu is also a member of the Simmons Cancer Center.

The research was supported by the Department of Defense Kidney Cancer Research Program (W81XWH-20-1-0905), a VA Merit Award (1 I01 BX004069-01), and a National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543).

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – April 30, 2025 – An FDA-designated orphan drug that can target a key vulnerability in lung cancer shows promise in improving the efficacy of radiation treatments in preclinical models, according to a study by UT Southwestern Medical Center researchers. The findings, published in Science Advances, suggest a new way to enhance the response to radiotherapy by inhibiting DNA repair in lung cancer cells.

“This study was motivated by challenges faced by millions of cancer patients undergoing radiation therapy, where treatment-related toxicities limit both curative potential and the patient’s quality of life,” said principal investigator Yuanyuan Zhang, M.D., Ph.D., Assistant Professor of Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Yuanyuan Zhang, M.D., Ph.D., is Assistant Professor of Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Prior research, including from the laboratory of co-investigator Ralph J. DeBerardinis, M.D., Ph.D., Professor and Director of the Eugene McDermott Center for Human Growth and Development, Professor in Children’s Medical Center Research Institute at UT Southwestern, and co-leader of the Cellular Networks in Cancer Research Program in the Simmons Cancer Center, has demonstrated that altered metabolic pathways in lung cancer cells allow them to survive, grow, and spread. But the role of metabolism in enhancing radiation efficacy has not been thoroughly explored. 

To identify metabolic pathways that allow cancer cells to survive radiation therapy, researchers conducted an unbiased CRISPR screen that identified lipoylation, a crucial process for mitochondrial enzyme function. Further investigation linked lipoylation deficiency to impaired DNA repair in cancer cells.

Lipoylation can be inhibited by the drug CPI-613, also known as devimistat, which received orphan drug status from the Food and Drug Administration (FDA). Orphan drugs are used to treat rare conditions and come with certain incentives to encourage their development given their small patient population. However, CPI-613 has not been found to improve outcomes on its own among patients with non-small cell lung cancer or in combination with surgical approaches in pancreatic cancer. In this study, researchers paired the drug with radiation to measure its effects in cancer cell lines and in mouse models of lung cancer.

Ralph J. DeBerardinis, M.D., Ph.D., is Professor and Director of the Eugene McDermott Center for Human Growth and Development and Professor in Children’s Medical Center Research Institute at UT Southwestern. He holds the Eugene McDermott Distinguished Chair for the Study of Human Growth and Development and the Philip O’Bryan Montgomery Jr., M.D., Distinguished Chair in Developmental Biology and is a Sowell Family Scholar in Medical Research.

“This study demonstrates for the first time that inhibiting lipoylation enhances lung cancer cells’ response to radiotherapy, offering a clinically translatable strategy using a clinically tested drug,” Dr. Zhang said.

Other UTSW contributors include first author Jui-Chung Chiang, Ph.D., postdoctoral researcher in the Zhang Lab; John D. Minna, M.D., Director and Professor of the Hamon Center for Therapeutic Oncology Research and co-leader of the Experimental Therapeutics Research Program in the Simmons Cancer Center; Robert D. Timmerman, M.D., Chair and Professor of Radiation Oncology; Anthony Davis, Ph.D., Associate Professor of Radiation Oncology; Zengfu Shang, Ph.D., Assistant Professor of Radiation Oncology; Ling Cai, Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health; Feng Cai, Ph.D., Assistant Professor in Children’s Medical Center Research Institute at UT Southwestern; and Wei-Min Chen, Ph.D., postdoctoral researcher in Radiation Oncology.

Drs. DeBerardinis, Ling Cai, Davis, Minna, and Timmerman are members of the Simmons Cancer Center. Dr. DeBerardinis is a Howard Hughes Medical Institute Investigator and holds the Eugene McDermott Distinguished Chair for the Study of Human Growth and Development and the Philip O’Bryan Montgomery Jr., M.D., Distinguished Chair in Developmental Biology and is a Sowell Family Scholar in Medical Research.

This research was supported by the Howard Hughes Medical Institute Investigator Program, grants from the National Institutes of Health (R35CA220449, P50CA196516, P50CA070907, and P30CA142543), the Moody Foundation (Robert L. Moody, Sr. Faculty Scholar Award), Jerry and Emy Lou Baldridge, the ASCO Young Investigator Award, the Lung SPORE Career Enhancement Award, a Distinguished Research Award from the President’s Research Council, American Cancer Society Institutional Research Grant (IRG-21-142-16), National Cancer Institute Cancer Center Support Grant (P30CA142543), the National Center for Advancing Translational Sciences of the National Institutes of Health (KL2TR003981 and CTSA-PP-YR1-D-009), Startup Award from UT Southwestern Department of Radiation Oncology, the Once Upon a Time Foundation, and Cancer Prevention and Research Institute of Texas (CPRIT) grant (RP180770).

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – April 29, 2025 – Black and Hispanic children with high-risk neuroblastoma experience worse survival outcomes than their white peers, even when treated in frontline clinical trials, according to a study led by a UT Southwestern Medical Center researcher. Published in JAMA Network Open, the study is believed to be the first to comprehensively evaluate survival by race and ethnicity in a national cohort of children with high-risk neuroblastoma enrolled in clinical trials. 

Neuroblastoma is a type of cancer that involves immature nerve cells and is the most common extracranial solid tumor in children.

Puja Umaretiya, M.D., M.S., is Assistant Professor of Pediatrics in the Division of Hematology and Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“The findings show that access to clinical trials alone is insufficient to overcome the inferior survival outcomes experienced by Black and Hispanic children with cancer,” said lead author Puja Umaretiya, M.D., M.S., Assistant Professor of Pediatrics in the Division of Hematology and Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Although racial and ethnic differences in childhood cancer survival have been previously documented, those datasets often lack important clinical treatment details to help understand why they occur. By using data from the Children’s Oncology Group, the research team was able to move beyond access and examine whether there are variations in survival even after accounting for access to highly specialized care as part of a clinical trial. The team also leveraged clinical trial data to examine potential mechanisms contributing to these differences in outcomes. 

The study analyzed data from two cohorts of children with high-risk neuroblastoma, including 696 children on chemotherapy induction/consolidation studies and 935 children on post-consolidation studies through the Children’s Oncology Group. The study found that Hispanic children had a nearly 80% higher hazard of death after treatment on induction trials compared to white patients after adjusting for tumor characteristics. In post-consolidation trials, both Black and Hispanic children had significantly lower survival rates than white children, even after researchers accounted for disease biology and response to early treatment.

The team found no significant racial or ethnic differences in care, including a lack of any delays during chemotherapy.

Dr. Umaretiya noted that her earlier research has shown children from racially and ethnically marginalized groups participate in frontline neuroblastoma trials at rates similar to white children. Despite this comparable access, racial and ethnic survival differences persist.

“These data identify the need for studies focused in two areas,” she said. “First, we need to be thoughtful about the data we collect on clinical trials to understand why marginalized groups do not experience the same outcomes. Collecting more specific data, such as social determinants of health, may provide insight into the underlying causes. Simultaneously, we need to embed supportive care interventions for groups at risk for worse outcomes despite standardized therapies.”

Previous work from Dr. Umaretiya’s team found that nearly three-quarters of Black and Hispanic families of children with cancer face at least one unmet health-related social need — such as food, housing, or transportation insecurity — which may affect outcomes.

“While further work is needed to understand disparate survival outcomes, any efforts to improve outcomes for children with cancer will likely need to focus on health-related social needs, which are highly prevalent and may contribute to worse outcomes in Black and Hispanic children,” Dr. Umaretiya said.

Sandi L. Pruitt, Ph.D., M.P.H., Professor in the Peter O’Donnell Jr. School of Public Health and Associate Director of Community Outreach and Engagement in the Simmons Cancer Center, also contributed to this study. Dr. Pruitt holds the Barrett Family Professorship in Cancer Research. 

The study was funded by the American Society of Clinical Oncology Young Investigator Award, a Children’s Oncology Group National Clinical Trials Network Statistics and Data Center grant (U10CA180899) and an Operations Center grant (U10CA180886), St. Baldrick’s Foundation, and the National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543).

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

Satwik Rajaram, Ph.D., is Assistant Professor in the Lyda Hill Department of Bioinformatics and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“There’s a real unmet need in the clinic to predict who will respond to certain therapies. Our work demonstrates that histopathological slides, a readily available resource, can be mined to produce state-of-the-art biomarkers that provide insight on which treatments might benefit which patients,” said Satwik Rajaram, Ph.D., Assistant Professor in the Lyda Hill Department of Bioinformatics and member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Rajaram co-led the study with Payal Kapur, M.D., Professor of Pathology and Urology and a co-leader of the Kidney Cancer Program (KCP) at the Simmons Cancer Center.

Every year, nearly 435,000 people are diagnosed with clear cell renal cell carcinoma (ccRCC), making it the most common subtype of kidney cancer. When the disease metastasizes, anti-angiogenic therapies are often used for treatment. These drugs inhibit new blood vessels from forming in tumors, limiting access to molecules that fuel tumor growth. Although anti-angiogenic drugs are widely prescribed, fewer than 50% of patients benefit from them, Dr. Kapur explained, exposing many to unnecessary toxicity and financial burden.

Payal Kapur, M.D., is Professor of Pathology and Urology at UT Southwestern and a co-leader of the Kidney Cancer Program (KCP) at the Simmons Cancer Center.

No biomarkers are clinically available to accurately assess which patients are most likely to respond to anti-angiogenic drugs, she added, although a clinical trial conducted by Genentech suggested that the Angioscore (a test that assesses the expression of six blood vessel-associated genes) may have promise. However, this genetic test is expensive, is hard to standardize among clinics, and introduces delays in treatment. It also tests a limited part of the tumor, and ccRCC is quite heterogenous, with variable gene expression in different regions of the cancer.

To overcome these challenges, Drs. Kapur and Rajaram and their colleagues at the KCP developed a predictive method using AI to assess histopathological slides – thinly cut tumor tissue sections stained to highlight cellular features. These slides are nearly always part of a patient’s standard workup at diagnosis, and their images are increasingly available in electronic health records, said Dr. Rajaram, also Assistant Professor in the Center for Alzheimer’s and Neurodegenerative Diseases and the Department of Pathology.

Using a type of AI based on deep learning, the researchers “trained” an algorithm using two sets of data: one that matched ccRCC histopathological slides with their corresponding Angioscore, and another that matched slides with a test they developed that assesses blood vessels in the tumor sections.

A typical histopathologic slide image of kidney cancer tissue (left) has significant intra-slide heterogeneity, illustrated by the false coloring in the middle panel with two distinct regions. The dramatic change in blood vessels across these regions is marked as a green overlay.

Importantly, unlike many deep learning algorithms that don’t offer insight into their results, this approach is designed to be visually interpretable. Rather than producing a single number and directly predicting response, it generates a visualization of the predicted blood vessels that correlates tightly with the RNA-based Angioscore. Patients with more blood vessels are more likely to respond to therapy; this approach allows users to understand how the model reached its conclusions.

When the researchers evaluated this approach using slides from more than 200 patients who weren’t part of the training data – including those collected during the clinical trial that showed the potential value of Angioscore – it predicted which patients were most likely to respond to anti-angiogenic therapies nearly as well as Angioscore. The algorithm showed a responder will have a higher score than a non-responder 73% of the time compared to 75% with Angioscore. 

The study authors suggest AI analysis of histopathological slides could eventually be used to help guide diagnostic, prognostic, and therapeutic decisions for a variety of conditions. They plan to develop a similar algorithm to predict which patients with ccRCC will respond to immunotherapy, another class of treatments that only some patients respond to.

Other UTSW researchers who contributed to this study include first author Jay Jasti, Ph.D., former Data Scientist in the Rajaram Lab; James Brugarolas, M.D., Ph.D., Professor of Internal Medicine, Director of the Kidney Cancer Program, and a member of the Simmons Cancer Center; Dinesh Rakheja, M.D., Professor of Pathology and Pediatrics; Hua Zhong, Ph.D., Computational Biologist; Vandana Panwar, M.D., Medical Resident; Vipul Jarmale, M.S., Data Scientist; Jeffrey Miyata, B.S., Histology Technician; and Alana Christie, M.S., Biostatistical Consultant.

Dr. Kapur holds the Jan and Bob Pickens Distinguished Professorship in Medical Science, in Memory of Jerry Knight Rymer and Annette Brannon Rymer and Mr. and Mrs. W.L. Pickens.

The study was funded by the Department of Defense (KC200285), the Cancer Prevention and Research Institute of Texas (RP220294), the Lyda Hill Department of Bioinformatics, a National Institutes of Health-sponsored Kidney Cancer SPORE grant (P50CA196516), and a National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543).

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

DALLAS – April 14, 2025 – The STING protein, known for helping cells fight viral infections by generating inflammation, also appears to function as a quality control sensor for organelles that serve as cellular waste disposal systems, UT Southwestern Medical Center researchers found. Their study, published in Molecular Cell, helps explain critical features of diseases called lysosomal storage disorders and could eventually lead to new treatments for these and other neurodegenerative diseases.

Nan Yan, Ph.D., (right) Professor and Vice Chair of Immunology and Professor of Microbiology, co-led the study with Immunology graduate student Zhen Tang, B.S. Dr. Yan is an Investigator in the Peter O’Donnell Jr. Brain Institute and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He holds the Edwin L. Cox Distinguished Chair in Immunology and Genetics and is a Rita C. and William P. Clements, Jr. Scholar in Medical Research.

“STING is well known as an innate immune signaling protein. This study uncovered a new nonimmune function of STING,” said study leader Nan Yan, Ph.D., Professor and Vice Chair of Immunology and Professor of Microbiology at UT Southwestern.

There are more than 70 known lysosomal storage disorders (LSDs). These rare neurodegenerative diseases are characterized by the dysfunction of lysosomes, cellular organelles that break down various substances ready for disposal, including proteins, nucleic acids, and even other organelles, by digesting them in acid. This dysfunction allows substances that would normally be broken down to accumulate to harmful levels.

Inflammation in the nervous system is a prevailing symptom of these disorders. But why lysosomal dysfunction causes neuroinflammation has been unclear. In a 2021 study, Dr. Yan and colleagues showed that STING – short for stimulator of interferon genes – drives this symptom for one LSD, Niemann-Pick disease type C1 (NPC1).

To see whether STING is involved in other LSDs, Dr. Yan’s team at UTSW worked with a mouse model of an LSD called Krabbe disease with the same mutation found in human disease. In some of these animals, the researchers also deleted the gene for STING. Compared with animals that carried neither genetic defect, those with only the Krabbe mutation had a substantial increase in the activity of inflammatory genes, particularly in a type of nervous system cell called microglia. Consequently, they developed severe neuroinflammation by about a month of age. However, in those also missing the STING gene, this increased gene activity and neuroinflammation was substantially reduced.

Lu Sun, Ph.D., is Assistant Professor of Molecular Biology, an Investigator in the Peter O’Donnell Jr. Brain Institute, and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He is a Southwestern Medical Foundation Scholar in Biomedical Research.

The researchers saw a similar phenomenon in mouse models for two other LSDs – palmitoyl-protein thioesterase 1 deficiency and lysosomal chloride channel deficiency. These and other LSD mouse models in the study were provided by Steven Gray, Ph.D., UTSW Professor of Pediatrics, in the Eugene McDermott Center for Human Growth and Development, of Molecular Biology, and of Neurology, who is an expert on gene therapy for LSD patients.

These results suggested STING drives neuroinflammation when lysosomes become damaged, a finding the researchers corroborated when they dosed healthy cells with a chemical that damages lysosomes. A closer look at gene expression in cells derived from the animal models showed that STING also increased the activity of genes associated with lysosome repair and new lysosome generation. Additional experiments in collaboration with Lu Sun, Ph.D., Assistant Professor of Molecular Biology and an expert on glial cells, showed this phenomenon depends on a protein called transcription factor EB (TFEB), which acts as a master controller of several lysosome-related genes.

Because the STING protein has multiple functional regions spanning the cell membrane, the researchers did additional experiments to determine which region might be responsible for lysosome generation. They found that the region located squarely within the cell membrane was key for this function. This “transmembrane” region is known to house a channel that helps membranous vesicles, such as lysosomes, regulate pH – a measure of acidity or alkalinity – by transporting pH-lowering protons across the membrane. Opening this channel on acidic vesicles releases protons, increasing the pH inside the vesicles and activating TFEB.

Dr. Yan and his colleagues hypothesize that because lysosomes normally degrade STING continuously, since it’s perpetually generated in cells, STING accumulation signals cells to kickstart the lysosome repair and generation pathway. In LSDs, this accumulation also prompts STING to generate inflammation. Thus, finding a way to dampen STING’s inflammatory role while encouraging its lysosome repair and generation role could offer a new way to treat LSDs, Dr. Yan said. Because lysosome dysfunction is also a prominent feature of other neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS), this strategy eventually could be used to treat these conditions as well.

Dr. Yan holds the Edwin L. Cox Distinguished Chair in Immunology and Genetics and is a Rita C. and William P. Clements, Jr. Scholar in Medical Research. Dr. Sun is a Southwestern Medical Foundation Scholar in Biomedical Research. Both are Investigators in the Peter O’Donnell Jr. Brain Institute and members of the Harold C. Simmons Comprehensive Cancer Center.

Other UTSW researchers who contributed to this study include first author Zhen Tang, B.S., Cong Xing, B.S., Antonina Araszkiewicz, M.S., and Devon Jeltema, B.S., all Immunology graduate students; Kun Yang, M.D., Ph.D., Instructor of Immunology; Wanwan Huai, Ph.D., postdoctoral fellow; Nicole Dobbs, Ph.D., Senior Scientist and Manager of the Yan Lab; and Yihe Zhang, B.S., Genetics, Development, and Disease graduate student.

This study was funded by grants from the National Institutes of Health (AI151708, AI185226, and NS122825) and UT Southwestern Endowed Scholar funds.

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – April 09, 2025 – Using a novel method that gives a readout of which proteins are in specific locations within cells, UT Southwestern Medical Center researchers have identified a protein that plays a key role in cell adhesion and movement. Their findings, published in Cell Reports, could help researchers better understand diverse phenomena such as cancer metastasis and cell differentiation.

“Our lab has a longstanding interest in understanding how cells are spatially organized. This work developed a new biochemical method that uncovered the function of a poorly characterized protein called calmin,” said W. Mike Henne, Ph.D., Associate Professor of Cell Biology and Biophysics and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He co-led the study with first author Holly Merta, Ph.D., a postdoctoral researcher in the Henne Lab.

Dr. Merta explained that she, Dr. Henne, and their colleagues were originally interested in better understanding how proteins are organized in the endoplasmic reticulum (ER), a cellular organelle with a broad range of functions including storing calcium, synthesizing some lipids and cholesterol, and transporting proteins to other cellular locations. Because the proteins performing these functions are thought to be organized into discrete locations within the ER, the researchers wanted to learn which proteins are found within these different locations.

W. Mike Henne, Ph.D., Associate Professor of Cell Biology and Biophysics, is a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

To do this, they developed an approach called sub-organelle spatial proteomics by combining the gene editing tool CRISPR with TurboID, an enzyme that adds a chemical tag onto all proteins that are in close proximity. These tagged proteins can then be isolated and identified. By strategically anchoring TurboID onto different proteins known to localize in specific regions of the cell interior, researchers can create a “map” of the protein landscape.

The researchers fused TurboID to four proteins known to be in different subregions of the ER, then worked with UTSW’s Proteomics Core to identify all the tagged proteins. When they examined which proteins were located in the ER’s membrane tubules, they were surprised to find calmin, a protein whose function was previously unknown.

A closer look showed calmin appeared to bind to F-actin, a protein that’s part of the cytoskeleton – a network of fibers that helps cells hold their shape, move, and connect with surfaces through sticky junctions called focal adhesions. When the researchers used a genetic trick to deplete calmin in motile cells, the cells moved significantly slower and developed more focal adhesions. Causing cells to overproduce calmin had the opposite effect.

Holly Merta, Ph.D., is a postdoctoral researcher in the Henne Lab at UT Southwestern.

Together, these findings suggested calmin is necessary to break down the F-actin fibers responsible for stabilizing focal adhesions, increasing adhesion turnover. Further experiments suggest calmin does this by increasing molecular signaling that relies on calcium stored in the ER.

Because calmin is often mutated in cancers, Drs. Henne and Merta said this protein may be pivotal for metastasis, the spread of cancer cells beyond the original tumor. Increasing focal adhesions could help metastatic cells survive in their new anatomical locations, establishing secondary tumors. Calmin has also been identified in developing neurons, where it may be important for growing the long extensions characteristic of these cells. The researchers plan to investigate these possibilities in future studies.

Other UTSW scientists who contributed to this study include Gaudenz Danuser, Ph.D., Chair and Professor of the Lyda Hill Department of Bioinformatics and Professor of Cell Biology; Arun Radhakrishnan, Ph.D., Professor of Molecular Genetics; Tadamoto Isogai, Ph.D., Assistant Professor in the Lyda Hill Department of Bioinformatics; Achinta Sannigrahi, Ph.D., postdoctoral researcher; and Kaitlynn Gov, B.S., graduate student researcher.

Dr. Henne holds the Martha Lee Foster Professorship in Brain Science and Medicine and is a W. W. Caruth, Jr. Scholar in Biomedical Research.

This study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK126887), the National Institute of General Medical Sciences (GM119768 and GM145399), the National Institutes of Health (HL160487, AI158357, T32 DK007307, F32 GM154450, and 1S10OD028630-01); The Welch Foundation (I-1873 and I-1793), the UT Southwestern Medical Center Endowed Scholars Program, the Leducq Foundation (19CVD04), and a National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543).

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – April 08, 2025 – A preclinical model developed at UT Southwestern Medical Center that recapitulates a rare infant-onset form of diabetes suggests the condition stems from gradual damage to the pancreas through misregulation of a molecular pathway called the unfolded protein response (UPR). The findings, published in Molecular Metabolism, could one day lead to new ways to treat more common subsets of diabetes, including Types 1 and 2, which affect hundreds of millions worldwide.

Amanda Casey, Ph.D., is Assistant Professor of Molecular Biology at UT Southwestern.

“Our findings from this model, which carries the same genetic mutation as in human disease, provide insights into how beta cells may become dysfunctional during diabetes,” said Amanda Casey, Ph.D., Assistant Professor of Molecular Biology at UT Southwestern. Dr. Casey co-led the study with Kim Orth, Ph.D., Professor of Molecular Biology and Biochemistry and a Howard Hughes Medical Institute Investigator, and Jun Wu, Ph.D., Associate Professor of Molecular Biology. Drs. Orth and Wu are members of the Harold C. Simmons Comprehensive Cancer Center at UTSW.

Neonatal diabetes affects an estimated 1 in 90,000-to-160,000 live births worldwide. Researchers have identified several single-gene mutations that cause this condition. One such mutation occurs in the gene encoding FicD, an enzyme that regulates the activity of BiP, a protein that helps fold other proteins into the shapes they need to function.

Under normal conditions, FicD precisely controls BiP by switching it between active and inactive states, allowing cells to respond to changing demands. When FicD is mutated, it loses this regulatory activity, resulting in permanent inactivation of BiP. This persistent BiP inactivation leads to the buildup of unfolded proteins inside cells, chronically activating the UPR.

Kim Orth, Ph.D., is Professor of Molecular Biology and Biochemistry at UT Southwestern and a member of the Harold C. Simmons Comprehensive Cancer Center. She is a Howard Hughes Medical Institute Investigator, holds the Earl A. Forsythe Chair in Biomedical Science, and is a W.W. Caruth, Jr. Scholar in Biomedical Research.

To determine how mutated FicD causes neonatal diabetes, Drs. Casey and Orth worked with the Wu Lab to develop a mouse line that carries the same genetic mutation as humans with this disease. Surprisingly, the mice appeared normal at birth, Dr. Orth said. But by 5 weeks of age, the mice developed high blood sugar and low levels of circulating insulin – hallmarks of diabetes.

When the researchers searched for signs of UPR throughout tissues in the rodents’ bodies, they saw hyperactivation of this molecular pathway in both the liver and pancreas, with pancreatic function significantly more affected. A closer look at mice with the mutation showed that pancreatic cells gradually lost the organized structure typical of healthy tissue. Although the insulin-producing pancreatic beta cells didn’t die, they appeared to lose the gene expression necessary to produce insulin, leading to a gradual decrease in levels of this critical blood sugar-regulating hormone over time.

Jun Wu, Ph.D., is Associate Professor of Molecular Biology at UT Southwestern and a member of the Harold C. Simmons Comprehensive Cancer Center. He is a Virginia Murchison Linthicum Scholar in Medical Research.

Dr. Casey noted that a misregulated UPR has been found to play a role in both Type 1 and Type 2 diabetes. It’s unclear why the pancreas is unusually susceptible to damage from glitches in this molecular pathway. But if scientists can find a way to protect the pancreas from UPR-related damage, she said, they might be able to protect this organ from progressive damage in patients with diabetes, allowing its beta cells to continue producing insulin.

Other UTSW researchers who contributed to this study are Bret Evers, M.D., Ph.D., Assistant Professor of Pathology and Ophthalmology; Nathan Stewart, B.S., and Naqi Zaidi, B.S., Research Technicians; Hillery Gray, B.A., Orth Lab Manager; Hazel A. Fields, Registered Histotechnologist, Lab Technical Assistant; Masahiro Sakurai, Ph.D., Research Scientist; and Carlos Pinzon-Arteaga, D.V.M., Ph.D., Research Associate.

This study was funded by grants from The Welch Foundation (I-1561), Once Upon a Time Foundation, the National Institutes of Health (R35 GM134945, R21 1R21EY034597-01A1, GM138565-01A1, and HD103627-01A), UTSW Nutrition & Obesity Research Center (under National Institute of Diabetes and Digestive and Kidney Diseases/NIH award number P30DK127984), and New York Stem Cell Foundation.

Dr. Orth holds the Earl A. Forsythe Chair in Biomedical Science and is a W.W. Caruth, Jr. Scholar in Biomedical Research. Dr. Wu is a Virginia Murchison Linthicum Scholar in Medical Research.

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

Female mosquito salivary glands could unlock key to malaria transmission

Malaria, responsible for hundreds of thousands of deaths each year worldwide, is caused by a parasite transmitted through the salivary glands of female Anopheles mosquitoes. Understanding the biology of these tissues is critical to developing new treatments for the disease, found mostly in tropical countries. Mosquitoes have an internal 24-hour clock that controls a variety of behaviors, including pheromone production, swarming, and mating. However, it has been unknown whether their salivary glands operate on a cyclic daily schedule.

To answer this question, researchers including Joseph Takahashi, Ph.D., Chair and Professor of Neuroscience at UT Southwestern Medical Center and an Investigator in the Peter O’Donnell Jr. Brain Institute, examined gene activity in Anopheles salivary glands. According to their findings, reported in Nature Microbiology, about half of the mosquitoes’ salivary gland genes had rhythmic expression, particularly those important for efficient feeding, such as genes that make anticlotting proteins. The researchers also found that the mosquitoes preferred to feed at night, with the blood volume they ingested varying cyclically throughout the day.

Additionally, genes of the parasites living in Anopheles salivary glands had cyclic differences in activity, especially those involved in parasite transmission. The authors suggest the internal clocks of the parasite, mosquito, and mammalian host play an important role in successful malaria infection.

Study senior author Filipa Rijo-Ferreira, Assistant Professor of Infectious Diseases and Vaccinology at the University of California, Berkeley, is a former postdoctoral researcher in the Takahashi Lab at UTSW.

Nanoparticles extend glioblastoma survival in phase one trial

Despite decades of research to develop effective treatments, the median survival for glioblastoma – the most common malignant primary brain tumor in adults – is just 15-18 months after diagnosis. One reason for this grim statistic is that these tumors invariably recur despite aggressive, multimodality treatments. Although traditional radiation treatments can delay recurrence and extend survival, they often damage healthy brain tissue, negatively affecting quality of life. Preclinical research has suggested radiation-emitting nanoparticles targeting tumor-containing regions through convection enhanced delivery (CED), bypassing the blood-brain barrier, could effectively treat these tumors.

In a phase one clinical trial reported in Nature Communications, two researchers from UT Southwestern and their colleagues showed this strategy was safe and effective. The team worked with 21 patients at medical centers, including UTSW, who had recurrent glioblastoma. They were divided into six groups, each of which received a different dose of radiation-emitting nanoparticles through CED. Patients who received the highest doses had tolerable side effects and lived an average of 17 more months after treatment, significantly longer than expected for patients with recurrent glioblastoma. The authors suggest this strategy shows promise for improving treatments for these patients.

UTSW researchers who contributed to this study are Toral Patel, M.D., Associate Professor of Neurological Surgery, and Michael Youssef, M.D., Assistant Professor of Neurology. Drs. Patel and Youssef are members of the O’Donnell Brain Institute and the Harold C. Simmons Comprehensive Cancer Center at UTSW.

Alternate antidepressant not effective for Alzheimer’s agitation

Up to 60% of people with Alzheimer’s disease experience agitation, a symptom that can be a significant burden for caregivers. Nondrug treatments are recommended as first-line interventions. Citalopram, a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for anxiety and depression, has shown promise for treating Alzheimer’s-induced agitation in patients whose symptoms don’t respond to other therapies. However, this drug has been linked to cardiac and cognitive risks. More specifically, citalopram consists of two compounds that are mirror images, R- and S-citalopram, and it is thought that the R-compound is linked to these risks.

Hoping to reap the same benefits without these risks, researchers in the U.S. and Canada evaluated the S-compound on its own, an available SSRI called escitalopram, in a phase three clinical trial. Results reported in Nature Medicine by Tarek Rajji, M.D., Chair and Professor of Psychiatry and in the O’Donnell Brain Institute at UT Southwestern, and colleagues showed that escitalopram was not effective in treating Alzheimer’s agitation. The drug also was associated with significant side effects including falls, diarrhea, and heart problems.

The authors suggest that citalopram should remain the preferred SSRI for treating Alzheimer’s-related agitation.

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.