DALLAS – Oct. 22, 2025 – Researchers have identified factors associated with survival for patients initially diagnosed with metastatic breast cancer who were seen at UT Southwestern Medical Center and its affiliated sites. Their findings, published in Communications Medicine, list certain demographic and clinical characteristics to consider among the regional population when formulating treatment plans for individual patients.

“Understanding local risk factors and regional practice patterns can guide more nuanced multidisciplinary care, helping clinicians identify patients at risk for worse outcomes and provide more personalized management,” said Isaac Chan, M.D., Ph.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

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

Researchers elsewhere have built national datasets that include information from thousands of patients to search for insights into metastatic breast cancer to better understand which individuals are at risk for poor outcomes. However, Dr. Chan explained, such large numbers can obscure findings that may be specific to local populations.

To overcome this issue, he and his colleagues developed the Dallas Metastatic Cancer Study, a database that has tracked patients with metastatic disease treated at UT Southwestern and affiliated sites, including Parkland Health, since 2010. Pulling data for patients who were first diagnosed with metastatic breast cancer between 2010 and 2021, the researchers examined clinical and demographic features, searching for those that correlated with decreased length of survival.

Their findings showed that patients who were Black, had public insurance or no health insurance, had underlying metabolic diseases such as high blood pressure or diabetes, or had cancer that metastasized to specific organs, including the brain, liver, or lungs, tended to die earlier than those without these factors.

Why these variables are associated with reduced survival will be the focus of future research, Dr. Chan said. In the meantime, he added, doctors may be able to improve survival by keeping a closer eye on patients with these risk factors.

Dr. Chan, who is also Assistant Professor of Molecular Biology, co-led the study with former trainees Hannah Chang, M.D., a member of the Chan Lab who is now an Assistant Professor of Medical Oncology & Therapeutics Research at City of Hope, and Meng Cao, M.D., medical resident. This is the first published study of the Chan Lab’s Metastasis Research Program.

Other UTSW researchers who contributed to this study are Mir Lim, M.D., Ariana Weiss, M.D., Danielle Martinez, M.D., Giselle Uwera, M.D., Jonathan Ladner, M.D., Priscilla Okanlawon, M.D., Ruchita Iyer, M.D., and Luis Chinea, M.D., medical residents; Anna Moscowitz, M.D., and Sangeetha Reddy, M.D., Assistant Professors of Internal Medicine; Ang Gao, M.S., Biostatistical Consultant; Katherine Lei, B.A., medical student; Heather McArthur, M.D., Professor of Internal Medicine and Clinical Director of the Breast Cancer Program at Simmons Cancer Center; and Sakshi Mohta, B.S., and Shao-Po Huang, B.S., graduate student researchers.

Drs. Reddy and McArthur are also members of Simmons Cancer Center.

This study was funded by the National Institutes of Health (1K08CA270188-01A1), a METAvivor Early Career Investigator Award, a Susan G. Komen Career Catalyst Research Grant (1010879), a Mary Kay Ash Foundation Cancer Research Grant (11-23), a Robert J. & Claire Pasarow Foundation Award, and a National Cancer Institute 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, 25 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.

With the elections, UT Southwestern has 25 members of the National Academy of Medicine – more than any other institution in Texas – along with 24 members of the National Academy of Sciences (NAS) and 13 Howard Hughes Medical Institute (HHMI) Investigators.

Dr. Pan is recognized for advancing the understanding of the molecular pathways that regulate tissue growth and homeostasis, while Dr. Mendell has led pioneering research into the functions of noncoding RNAs in both normal physiology and diseases such as cancer. Both investigators are members of the Harold C. Simmons Comprehensive Cancer Center, where their discoveries continue to shape innovative approaches to cancer treatment and deepen our understanding of tumor biology.

“The elections of Dr. Mendell and Dr. Pan to the National Academy of Medicine reflect the depth and significance of their scientific contributions to our understanding of cancer biology,” said Daniel K. Podolsky, M.D., President of UT Southwestern and a member of the NAM. “Dr. Mendell’s work has illuminated the role of microRNAs in tumor development, leading to promising therapeutic strategies, while Dr. Pan’s discoveries related to tumor suppressor genes have advanced the use of targeted inhibitors to control cancer growth. This recognition underscores the impact of their research for its potential to ultimately lead to more effective therapies.”

Joshua Mendell, M.D., Ph.D.

Joshua Mendell, M.D., Ph.D., is Vice Chair and Professor of Molecular Biology at UT Southwestern. He holds the Charles Cameron Sprague, M.D. Chair in Medical Science.

Charles Cameron Sprague, M.D. Chair in Medical Science

Dr. Mendell, an HHMI Investigator, joined UT Southwestern in 2011 from the Johns Hopkins University School of Medicine. He serves as Vice Chair in the Department of Molecular Biology and is a member of the Hamon Center for Regenerative Science and Medicine.

The Mendell Lab investigates fundamental aspects of post-transcriptional gene regulation, noncoding RNA regulation and function, and the roles of these pathways in normal physiology, cancer, and other diseases. In 2005, he and his colleagues uncovered the first example of a vertebrate transcription factor that regulates the expression of microRNAs (miRNAs), a type of noncoding RNA. This study was important for establishing the principle that miRNAs have been functionally integrated into core cancer pathways.

Dr. Mendell’s team further defined the roles of miRNAs in several critical oncogenic and tumor suppressor pathways. They have translated these findings into novel therapeutic approaches, most notably through demonstrating that systemic delivery of miRNAs potently suppresses the growth of tumors in mouse cancer models without toxicity. Most recently, Dr. Mendell and his colleagues have used high-throughput approaches to investigate RNA biology and post-transcriptional regulation, a strategy they are now applying to diverse problems in the laboratory.

Dr. Mendell earned his undergraduate degree in biology from Cornell University and his Ph.D. and M.D. from Johns Hopkins. Previous honors include the Paul Marks Prize for Cancer Research (2019) and the Edith and Peter O’Donnell Award in Medicine from the Texas Academy of Medicine, Engineering, Science and Technology (2016).

“I am deeply honored to be elected to the National Academy of Medicine and join the ranks of the many accomplished UT Southwestern faculty who have previously been recognized with this distinction,” Dr. Mendell said. “This would not have been possible without the amazing trainees and staff who have worked in my laboratory over the last 20 years, as well as the support of our Chair, Eric Olson, Ph.D., my colleagues in the Department of Molecular Biology, and the broader UT Southwestern community. I feel very fortunate to have an opportunity to lead a research team at this remarkable institution.”

Duojia Pan, Ph.D.

Duojia Pan, Ph.D., is Chair and Professor of Physiology at UT Southwestern. He holds the Fouad A. and Val Imm Bashour Distinguished Chair in Physiology.

Fouad A. and Val Imm Bashour Distinguished Chair in Physiology

Dr. Pan, who is also a member of the NAS and an HHMI Investigator, first joined the UT Southwestern faculty in 1998. Recruited to Johns Hopkins in 2004, he returned to UT Southwestern in 2016 as Chair of the Department of Physiology.

Dr. Pan is best known for his foundational discoveries of the Hippo signaling pathway that controls animal tissue growth. Using the fruit fly Drosophila as a model, the Pan Lab made a series of discoveries that defined, in a stepwise manner, the key molecular events in the Hippo signaling pathway. Most recently, his lab revealed a surprising role for Hippo signaling in regulating cell aggregation and density in a close unicellular relative of animals.

In addition, the Pan Lab elucidated the molecular function of the Tsc1 and Tsc2 tumor suppressor genes, linking Tsc1/Tsc2 to Rheb and TOR signaling. This work provided the key molecular insight for the use of mTOR inhibitors in the treatment of tuberous sclerosis, a genetic disease that can lead to tumor development in multiple tissues.

Dr. Pan earned his undergraduate degree in biochemistry from Peking University in 1988 and his Ph.D. from the University of California, Los Angeles in 1993. He completed his postdoctoral training at the University of California, Berkeley. Previous honors include the Passano Award (2022) and the Paul Marks Prize for Cancer Research (2013).

“I am deeply honored and humbled to be elected to the National Academy of Medicine,” Dr. Pan said. “This is a recognition of the creativity, hard work, and team efforts of my laboratory over the last 27 years. Our work started at UT Southwestern when I was an Assistant Professor. I am extremely grateful for the superb scientific environment at UT Southwestern.”

Founded in 1970 as the Institute of Medicine, the NAM is one of three academies that make up the National Academies of Sciences, Engineering, and Medicine in the United States. Operating under the 1863 Congressional charter of the National Academy of Sciences, the National Academies are private, nonprofit institutions that work outside of government to provide objective advice on matters of science, technology, and health. 

For a complete list of NAM members at UTSW, please visit our Legacy of Excellence in Science & Medicine page.

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, 25 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 – Oct. 16, 2025 – The ultimate cause of death from cancer may not be metastatic disease, as researchers have long surmised, but an infiltration of tumors into major blood vessels that cause blood clots and multiorgan failure, a one-of-a-kind clinical study led by UT Southwestern Medical Center suggests. These findings, published in Nature Medicine, could spur interventions that extend the lives of patients with advanced cancers.

Matteo Ligorio, M.D., Ph.D., is Assistant Professor of Surgery and in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“The big question we were trying to answer: What kills cancer patients? Why do they die one specific day rather than six months earlier or later?” said Matteo Ligorio, M.D., Ph.D., Assistant Professor of Surgery and in the Harold C. Simmons Comprehensive Cancer Center. Dr. Ligorio led the study along with Kelley Newcomer, M.D., Associate Professor of Internal Medicine at UT Southwestern, and Nicola Aceto, Ph.D., Professor of Molecular Oncology at ETH Zurich in Switzerland.

Cancer claims about 600,000 people in the U.S. each year. However, what actually ends their lives has been a mystery, Dr. Ligorio explained. Although scientists have long proposed that cancer mortality is caused by the spread of tumors throughout the body – a phenomenon known as metastasis – patients often live with metastatic disease for years, suggesting that this may not be what instigates the clinical decline that ultimately leads to death.

Some studies have shown that cancer patients are more likely to develop blood clots in their heart, liver, and lungs, indicating that the cardiovascular system is altered in advanced malignancies. But whether this factor contributes to their demise has been unknown.

Kelley Newcomer, M.D., is Associate Professor of Internal Medicine at UT Southwestern.

To investigate this question, Drs. Newcomer and Ligorio analyzed a retrospective cohort of more than 100 patients with colorectal, lung, ovarian, liver, or pancreatic cancer who had died at William P. Clements Jr. University Hospital and Parkland Health and undergone routine autopsies. Dr. Newcomer then recruited 31 terminally ill patients who were in hospice: 21 with solid tumors and 10 with other conditions. Over the following weeks, she monitored and examined these patients. Dr. Newcomer and Dr. Ligorio’s clinical team also took blood samples whenever the patients reported a significant change in their health status or when their score worsened on an assessment called the Palliative Performance Scale, one of the most commonly used bedside tools to determine the status of patients in palliative care settings.

When these patients died – an average of about 38 days after they were enrolled in the study – Dr. Ligorio performed a modified autopsy on each. While normal autopsy procedures tend not to maintain the integrity of all major blood vessels, his altered protocol preserved them so he could examine their walls and interiors.

The modified autopsies revealed that, unlike the patients who died of other causes, those with cancer typically had tumors penetrating the walls and extending into the interiors of major blood vessels, including the portal vein, inferior vena cava, hepatic veins, and/or abdominal aorta. In several cases where CT scans were available, these vessel-invading growths were present in the weeks or months preceding death, suggesting that such lesions may be detectable on routine imaging.

In addition, blood samples taken during the visits in the follow-up period and analyzed by Dr. Aceto’s team at ETH Zurich revealed a sharp uptick in the number of cancer cells in the bloodstream just before death, strengthening the massive involvement of the cardiovascular system during disease progression.

Together, these findings led Dr. Ligorio to a new theory on what kills cancer patients: When tumors – either primary or metastatic – impinge upon major blood vessels, microscopic pieces of the tumors may break off and join the bloodstream, making blood more likely to clot. Clots that form through this process would restrict blood flow to organs, leading to multiorgan failure that ultimately causes death.

To help validate this idea, researchers examined CT imaging data from 1,250 cancer patients who died that was collected by Dr. Ligorio’s collaborators at the University of Lubeck and the University of Mainz in Germany. Dario Ghersi, M.D., Ph.D., Associate Professor at the University of Nebraska at Omaha, and William Gasper, Ph.D., a graduate student at the University of Nebraska at Omaha at the time of this research, co-led these analyses with Dr. Ligorio, Dr. Newcomer, and Dr. Aceto. They confirmed that most of these patients had tumors infiltrating major blood vessels, supporting this new theory of cancer progression.

“Surgery or radiation to treat tumors approaching large blood vessels could potentially transform how we diagnose, manage, and treat patients with cancers,” Dr. Newcomer said.

Drs. Newcomer and Ligorio thanked the patients and their families who generously agreed to participate in this study to advance the scientific understanding of cancer and support the development of new treatments. They also expressed gratitude to the three hospice organizations — Visiting Nurse Association of Texas, Faith Presbyterian Hospice, and Pathway Hospice — for their collaboration in this clinical study.

Dr. Ligorio and Dr. Newcomer are now designing clinical trials, along with Herbert J. Zeh III, M.D., Chair and Professor of Surgery at UTSW, to test these therapeutic approaches and determine whether targeting tumor-vessel infiltration can substantially extend survival, including in patients with advanced disease.

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

This study was funded by grants from the Cancer Prevention and Research Institute of Texas (RR200023), the National Cancer Institute (NCI) (5R37CA242070), the American-Italian Cancer Foundation Post-Doctoral Research Fellowship, the European Research Council (101001652), the strategic focus area of Personalized Health and Related Technologies at ETH Zurich (PHRT-960), the Swiss National Science Foundation (212183), the Swiss Cancer League (KLS-5636-08-2022), the ETH Zurich Lymphoma Challenge (LC-02-22), the ETH Zurich, 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 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 – Oct. 15, 2025 – Activating specific neurons in a part of the brain that serves as the body’s master circadian pacemaker caused mice to eat significantly more during a time of day when they would normally be at rest, a UT Southwestern Medical Center study shows. The findings, published in Cell Reports, could lead to new strategies to help people lose weight, including night shift workers who have a higher prevalence of obesity.

“We identify for the first time a distinct set of neurons in the brain that controls feeding and metabolism during one specific time of day and accounts for a small but not insignificant proportion of body weight,” said Jeffrey Zigman, M.D., Ph.D., Professor of Internal Medicine and Psychiatry at UT Southwestern. Dr. Zigman co-led the study with first author Omprakash Singh, Ph.D., a postdoctoral researcher in the Zigman Lab.

Jeffrey Zigman, M.D., Ph.D., is a Professor of Internal Medicine and Psychiatry, a member of the Center for Hypothalamic Research and the Harold C. Simmons Comprehensive Cancer Center, and an Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern. He holds the Kent and Jodi Foster Distinguished Chair in Endocrinology, in Honor of Daniel Foster, M.D.; the Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine; and The Diana and Richard C. Strauss Professorship in Biomedical Research.

Researchers have long known that eating impacts body weight differently depending on when food is consumed, Dr. Zigman explained. For example, eating late at night is associated with greater weight gain than eating the same amount during the day. This effect is especially apparent in night shift workers, who are more frequently overweight or obese despite caloric intake similar to day workers.

These observations suggest specific circuits of neurons that affect feeding and metabolism might operate differently at various times of the day. Dr. Zigman, Dr. Singh, and their colleagues hypothesized that one such circuit might be in the suprachiasmatic nucleus (SCN), a part of the brain that sets circadian rhythms throughout the body based on light received through the eyes.

Previous research in the Zigman Lab showed that some SCN neurons are stimulated by ghrelin, a hormone that prompts feeding and slows metabolism to encourage weight gain. However, the significance of these findings had been unclear.

To better understand this population of SCN neurons, the researchers worked with mice genetically altered so the scientists could turn these neurons on and off. They found that if they turned on the neurons in the middle of the animals’ rest period – around 10 a.m., since mice are nocturnal – they ate more than two times as much as they usually do during this time. Turning the neurons off at this time reduced the already low amount of food typically consumed during this period.

Whether the neurons were on or off during other times of day or night had no effect on the rodents’ feeding behavior or weight. But turning the neurons off during their rest period for 15 straight days caused them to lose about 4.3% of their body weight, while mice with unaltered SCN neurons gained about 2.5%. These results suggest the activity of the ghrelin-stimulated SCN neurons is responsible for about 7% of body weight – a small but significant amount that could make a marked difference for overall health, Dr. Zigman said.

If these results also apply to humans, he added, they suggest that targeting the same population of neurons in the SCN could offer weight-loss benefits similar to those seen with some modern weight-loss drugs. This strategy could be especially beneficial for night shift workers and other groups to prevent or treat weight gain linked to nighttime eating.

Other UTSW researchers who contributed to this study are Kripa Shankar, Ph.D., Instructor in the Center for Human Nutrition and of Internal Medicine; Deepali Gupta, Ph.D., Instructor in the Peter O’Donnell Jr. Brain Institute and of Neuroscience; Luis Leon Mercado, Ph.D., Instructor of Internal Medicine; Sherri Osborne-Lawrence, M.S., Senior Research Scientist; Corine P. Richard, R.N.; Sepideh Sheybani-Deloui, Ph.D., and Salil Varshney, Ph.D., postdoctoral researchers; Soumya Kulkarni, B.S., Moyu Lyu, M.S., and Bingbing Li, B.S., graduate student researchers; Avi W. Burstein, high school student researcher; and Connor Lawrence, research assistant.

Dr. Zigman is a member of the Center for Hypothalamic Research and the Harold C. Simmons Comprehensive Cancer Center and an Investigator in the O’Donnell Brain Institute. He holds the Kent and Jodi Foster Distinguished Chair in Endocrinology, in Honor of Daniel Foster, M.D.; the Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine; and The Diana and Richard C. Strauss Professorship in Biomedical 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 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 – Oct. 13, 2025 – Using only text from doctors’ notes and radiology reports, an artificial intelligence (AI) program known as GPT-4o reliably identified patients’ types of strokes, UT Southwestern Medical Center researchers found. Their study, published in Stroke, could eventually lead to new ways to help guide doctors’ medical decisions in real time and reduce the heavy workload necessary to report data to patient registries.

Ann Marie Navar, M.D., Ph.D., is Associate Professor of Internal Medicine and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern.

“Large language models (LLMs) that can decipher unstructured text are an emerging AI technology with immense potential in medical research. Our study provides proof that these LLMs can abstract medical diagnoses from medical notes as well as human chart abstractors,” said Ann Marie Navar, M.D., Ph.D., Associate Professor of Internal Medicine and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern.

Dr. Navar co-led the study with Eric Peterson, M.D., M.P.H., Professor of Internal Medicine and in the O’Donnell School of Public Health, Vice Provost, and Senior Associate Dean for Clinical Research; and Dylan Owens, Ph.D., M.S., Postdoctoral Researcher.

Like most large academic medical centers, UTSW participates in several patient registries – systematic collections of data on specific conditions that researchers use for studies. One prominent example is the American Heart Association’s Get With The Guidelines-Stroke (GWTG-Stroke), a quality improvement initiative involving over 2,600 hospitals across the country. When patients are treated at one of these hospitals for stroke, trained nurses collect a wealth of information from their electronic health records, inputting the data into lengthy forms. This process requires an enormous amount of human labor.

Eric Peterson, M.D., M.P.H., is Professor of Internal Medicine and in the O’Donnell School of Public Health, Vice Provost, and Senior Associate Dean for Clinical Research at UT Southwestern. He holds the Adelyn and Edmund M. Hoffman Distinguished Chair in Medical Science.

To decrease this burden, Drs. Owens, Navar, and Peterson wondered whether LLMs – a form of AI designed to understand and generate human language – could be used for the same purpose. They started with a simple question: Could an LLM accurately determine stroke type based only on “unstructured” data found in electronic health records, such as notes and reports?

The researchers tested this idea with GPT-4o, an LLM introduced this year with capabilities beyond the more commonly used ChatGPT. Using electronic health records for 4,123 patients hospitalized for stroke at UT Southwestern and Parkland Health between January 2019 and August 2023, the team evaluated three types of prompts asking the LLM to distinguish each patient’s stroke type. Zero-shot chain-of-thought prompts encouraged the model to break complex queries into smaller, logical steps using minimal human input; expert-guided prompts incorporated tips from neurologists and cardiologists; and instruction-based prompts steered the model to evaluate patients’ records using GWTG-Stroke registry guidelines.

The researchers compared the results they received from GPT-4o with those recorded in registry reports for these patients in GWTG-Stroke. They found that all three LLM prompt styles accurately distinguished between the two major types of stroke – hemorrhagic and ischemic – and between hemorrhagic subtypes. However, accuracy was lower for some ischemic subtypes, such as cryptogenic strokes. This lower reliability reflects real-world difficulty in classifying these subtypes, which tend to be diagnoses of exclusion, Dr. Owens explained.

Dylan Owens, Ph.D., M.S., is a Postdoctoral Researcher at UT Southwestern.

Together, he said, the results suggest LLMs could be a useful tool for accurately abstracting some information from electronic health records for populating time-intensive registry forms and could be used to flag other data that need a closer look from human abstractors. Future research will focus on using LLMs to fill in other parts of registry forms, as well as the feasibility of using LLMs for clinical decision support – programs that aim to improve patient outcomes by delivering timely information to providers at the point of care.

Dr. Owens noted that UTSW researchers also have achieved success working with LLMs for other tasks such as matching patients with clinical trials, performing quality assessments while investigating opportunities for population health improvement, and automating extraction of clinical data for research.

Additional UTSW researchers who contributed to this study are Justin Rousseau, M.D., M.M.Sc., Associate Professor of Neurology and in the Peter O’Donnell Jr. Brain Institute and Deputy Chief Medical Informatics Officer for Neurosciences; Michael Dohopolski, M.D., Assistant Professor of Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center; and Danh Q. Nguyen, M.D., Clinical Fellow.

Dr. Peterson holds the Adelyn and Edmund M. Hoffman Distinguished Chair in Medical Science.

This study was funded by UT Southwestern Medical Center and grants from the National Institutes of Health (5T32HL12524710 and UL11R003163).

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 – Oct. 09, 2025 – Elevated calcium levels in the blood – a complication of kidney cancers known as hypercalcemia – may be successfully treated with a class of medications called HIF-2α inhibitors developed by UT Southwestern Medical Center, a new study shows. The findings, published in Cancer Discovery by a team at UTSW, offer hope to patients who develop this condition.

About 10% of patients with advanced kidney cancer develop hypercalcemia, which can cause confusion, muscle spasms, and seizures and is associated with lower patient survival. It’s typically treated with drugs like bisphosphonates that reduce calcium release from bone; however, these drugs have side effects, including osteonecrosis of the jaw, fractures, and an opposing complication called hypocalcemia, when blood calcium levels become too low.

Arijit Mal, Ph.D., is a postdoctoral researcher at UT Southwestern.

In their study, Arijit Mal, Ph.D., a postdoctoral researcher, and Bingqing Xie, Ph.D., Assistant Professor of Internal Medicine, along with senior investigator James Brugarolas, M.D., Ph.D., Professor of Internal Medicine in the Division of Hematology and Oncology and founding Director of the Kidney Cancer Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, evaluated the potential of HIF-2α inhibitors to block hypercalcemia at its root.

Bingqing Xie, Ph.D., is Assistant Professor of Internal Medicine at UT Southwestern.

Hypercalcemia is frequently caused by a hormone produced by kidney tumors called parathyroid hormone-related protein (PTHrP), which raises blood calcium levels. A previous study by the Brugarolas Lab showed that PTHrP production in kidney cancer is regulated by HIF-2, which led the investigators to test the role of HIF-2α-blocking drugs in hypercalcemia.

HIF-2α-blocking drugs are the result of a long journey at UT Southwestern. In the 1990s, Steven McKnight, Ph.D., Professor of Biochemistry, and David Russell, Ph.D., Professor Emeritus of Molecular Genetics, identified HIF-2α, the key component of HIF-2. Subsequent studies by Richard Bruick, Ph.D., and Kevin Gardner, Ph.D., then at UTSW, identified a vulnerability in the structure that they exploited with a chemical obtained from the UTSW chemical library. These results led to the founding of Peloton Therapeutics, which developed a series of related HIF-2α inhibitors: PT2399 for animal studies and PT2977/belzutifan, which the Food and Drug Administration approved to treat kidney cancer in 2023.

James Brugarolas, M.D., Ph.D., is Professor of Internal Medicine in the Division of Hematology and Oncology and founding Director of the Kidney Cancer Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

To determine whether inhibiting HIF-2α could treat hypercalcemia, researchers leveraged mice transplanted with human kidney tumors. They treated tumor-bearing mice that developed hypercalcemia with PT2399. Interestingly, the majority of the mice responded. Calcium levels dropped within just a few days of treatment onset, and symptoms, including weight loss, fatigue, and calcium deposition, subsided.

Additional studies showed that PT2399 prevents HIF-2α from binding to the gene that produces PTHrP, decreasing the amount of PTHrP made and explaining PT2399’s effects on hypercalcemia.

In a subsequent case study, a 63-year-old man with advanced clear cell renal cell carcinoma and elevated calcium was treated with PT2977/belzutifan. After treatment, PTHrP levels dropped, and calcium returned to normal levels within a few days without the side effects seen with standard therapies.

“Our study supports the systematic evaluation of HIF-2α inhibitors for kidney cancer patients with hypercalcemia,” Dr. Brugarolas said.

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

Dr. Brugarolas holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D., and is a member of the Cellular Networks in Cancer Research Program of the Simmons Cancer Center.

This study used kidney cancer tumor models developed by UTSW’s Kidney Cancer Program through a National Cancer Institute (NCI)-funded Specialized Program of Research Excellence award.

This study was funded by grants from the NCI (P50CA196516, R01CA245294, R01CA295997, P50CA196516, and P50CA070907), Department of Defense Congressionally Directed Medical Research Program’s Kidney Cancer Research Program (HT9425-25-1-0346), Cancer Prevention and Research Institute of Texas (RP230382, RP240516), National Institute of Diabetes and Digestive and Kidney Diseases through the UTSW Nutrition & Obesity Research Center (P30DK127984), and an NCI Cancer Center Support Grant (P30CA142543).

Disclosures: UT Southwestern and some of its researchers will receive financial compensation, through prior agreements with Peloton, based on belzutifan’s FDA approval.

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 – Oct. 06, 2025 – UT Southwestern Medical Center researchers have identified two distinct populations of cells known as antigen-presenting cancer-associated fibroblasts (apCAFs) that appear to support the survival and growth of malignant tumors. Their findings, reported in Cancer Cell, could one day lead to new therapies for notoriously hard-to-treat cancers, including pancreatic cancer and advanced colorectal cancer (CRC) that has spread throughout the abdomen, known as peritoneal metastasis.

Huocong Huang, M.D., Ph.D., is Assistant Professor of Surgery and Immunology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“We have uncovered two groups of fibroblasts integrated within tumors and defined their spatial microenvironment that control the mechanism of cancer growth, metastasis, and treatment resistance, suggesting a new strategy to therapeutically target a tumor’s supportive tissue,” said Huocong Huang, M.D., Ph.D., Assistant Professor of Surgery and Immunology at UT Southwestern. Dr. Huang co-led the study with Alex Kim, M.D., Ph.D., Assistant Professor of Surgery. Both are members of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Over the past two decades, researchers have had a growing understanding that cancerous tumors aren’t made only of cancer cells but instead are a heterogeneous mixture of many cell types. These include fibroblasts, which play vital roles in preserving tissue integrity, regulating inflammatory response, and facilitating wound repair. Although scientists initially thought that all cancer-associated fibroblasts (CAFs) were the same, advances in genetic profiling have shown that there are three subtypes.

In 2022, Dr. Huang’s team was among the researchers who discovered one of these subtypes, now known as apCAFs, in a mouse model of pancreatic cancer. Their findings showed that these cells express immune molecules on their surfaces and appear to regulate the activity of immune cells – called T cells – in tumors. However, little else was known about these cells, including whether they exist in human cancers, their origins in different cancer types, and where they tend to reside within tumors.

Alex Kim, M.D., Ph.D., is Assistant Professor of Surgery and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He is a Eugene P. Frenkel, M.D. Scholar in Clinical Medicine and Director of the Peritoneal Surface Malignancy Program.

To learn more, Dr. Huang, Dr. Kim, and their UTSW colleagues combined information from multiple existing datasets of human cancer single-cell RNA sequencing (scRNA-seq). The technique allows researchers to analyze gene activity at the level of individual cells, making it possible to distinguish different cell types. Using this wealth of data – generated from more than 2.5 million cells in 532 samples across 15 different cancer types – they generated an atlas of cell types found within these tumors.

These results not only confirmed the existence of apCAFs in most of the cancer types – suggesting that they may be universally present in human cancers – but also showed a particularly large number of these cells in both pancreatic cancers and CRC peritoneal metastases. Notably, the big data analysis revealed that the apCAFs themselves aren’t a uniform population but instead form two distinct groups: cells that appear to come from the mesothelium, a tissue that lines body cavities and internal organs, and others that appear to come from bone marrow.

These two populations seem to perform separate roles in the tumors, Dr. Huang explained. Spatial analysis showed that the mesothelium-associated apCAFs tended to be located near cancer cells, and the bone marrow-associated apCAFs tended to be located near immune cells called lymphocytes. Their locations suggest that the two apCAF types could influence tumor behavior by interacting with different kinds of cells.

Additional experiments showed that both types of apCAFs produce a protein called secreted phosphoprotein 1 (SPP1), which facilitates the growth and spread of cancer and promotes chemotherapy resistance. When the researchers removed SPP1 through genetic manipulation in mouse models of primary pancreatic cancer and CRC peritoneal metastasis, tumors grew and migrated far more slowly and became more sensitive to chemotherapy.

Together, these results suggest that apCAFs could represent new targets for treating cancer and that SPP1 could be both a target and a biomarker that doctors might use to track cancer progression. This is particularly important for patients diagnosed with peritoneal metastases of colorectal cancer, where diagnostic and treatment options are completely lacking, resulting in very poor patient outcomes, Dr. Kim said. SPP1-inhibiting drugs are already being tested in clinical trials for other diseases, and their use could potentially be translated to these cancer settings, he added.

“Our findings could lead to big opportunities to make a huge impact for patients with limited or no treatment options,” said Dr. Kim, a Eugene P. Frenkel, M.D. Scholar in Clinical Medicine and Director of the Peritoneal Surface Malignancy Program.

Other UTSW researchers who contributed to the study are first author Xiongfeng Chen, Ph.D., postdoctoral researcher; Herbert J. Zeh III, M.D., Chair and Professor of Surgery; Patricio M. Polanco, M.D., Professor of Surgery, Director of Robotic Surgery Training, Co-Director of the Pancreatic Cancer Program, and Co-Director of the Pancreatic Cancer Prevention Clinic; Zhuan Zhou, Ph.D., Assistant Professor of Surgery; Luyu “Amber” Xie, Ph.D., Pharm.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health; Zeynep Yazgan, B.S., Research Technician; Yang Liu, Ph.D., Research Scientist; Bo Zhang, M.S., Lab Manager; Kailiang Qiao, Ph.D., and Yiyue Jia, Ph.D., postdoctoral researchers; and Shunheng Liu, undergraduate student assistant.

Drs. Zeh, Polanco, and Zhou are also Simmons Cancer Center members.

This study was funded by the National Institutes of Health (R00 CA252009) 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.

Cerebrovascular Dynamics Index could help diagnose Alzheimer’s

The buildup of two pathological proteins, amyloid beta and phosphorylated tau, have long been considered hallmarks of Alzheimer’s disease. However, efforts to diagnose Alzheimer’s by searching for these proteins in spinal taps, PET imaging, and blood samples have drawbacks, including high cost and relatively low accuracy.

Research has shown that Alzheimer’s impairs vasomotor reactivity, in which the brain’s blood vessels dilate when carbon dioxide builds up in the blood. To determine whether this effect could be used to diagnose Alzheimer’s, two researchers from UT Southwestern Medical Center joined colleagues to develop the Cerebrovascular Dynamics Index (CDI). This noninvasive test uses Doppler ultrasound to measure blood flow velocity in some main arteries of the brain and near-infrared spectroscopy to measure oxygenation in the brain’s cortex.

Results from nearly 200 participants, published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, showed that the CDI distinguished among mild cognitive impairment, Alzheimer’s, and healthy individuals with better accuracy than existing methods. The authors say this test has significant promise to improve Alzheimer’s disease diagnosis and staging.

The study authors from UT Southwestern are Rong Zhang, Ph.D., Professor of Neurology, Biomedical Engineering, and Internal Medicine, an Investigator in the Peter O’Donnell Jr. Brain Institute, and Director of the Cerebrovascular Laboratory in the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Dallas; and Danilo Cardim, Ph.D., Instructor of Neurology.

Timed radiation extends survival for some non-small cell lung cancers

A subset of non-small cell lung cancer (NSCLC), the most common lung cancer type, has mutations in a molecule known as epidermal growth factor receptor (EGFR). Although EGFR-targeting drugs often work well initially to fight these cancers, most cases develop resistance and progress within two years. A study led by UT Southwestern researchers and published in eClinicalMedicine suggests that precisely timed radiation could be a useful additional treatment.

Results from a clinical trial involving 42 patients showed that highly targeted radiation therapy delivered eight weeks after drug initiation extended progression-free survival more than one year compared to outcomes seen with the drug alone. Patients on the new protocol also lived longer, with few additional side effects.

The study was led by Sawsan Rashdan, M.D., Associate Professor of Internal Medicine in the Division of Hematology and Oncology, and David Gerber, M.D., Professor of Internal Medicine and in the Peter O’Donnell Jr. School of Public Health. Dr. Rashdan is Director of Thoracic Medical Oncology Clinical Operations and a member of the Harold C. Simmons Comprehensive Cancer Center at UTSW. Dr. Gerber serves as Co-Director of Education and Training in the Simmons Cancer Center.

Investigating how airway cells respond to pathogens

Airway epithelial surfaces are the primary contact point for numerous infectious bacteria and viruses, including those that cause tuberculosis, measles, COVID-19, the common cold, and influenza. Rare epithelial microfold cells (M cells) can serve as an entry site and initiate early immune responses to these pathogens. Although M cells have been extensively studied in the intestines, little is known about their development and function in the airway.

To better understand these cells and how the body responds to airborne pathogens, UT Southwestern researchers and colleagues analyzed single cell gene expression to identify cell types in the adenoid – an airway immune organ where M cells are found – and defined their developmental trajectories and relationships. Their study in Mucosal Immunology identified 26 unique cell types and determined that airway M cells arise from progenitor club cells and have a distinct gene expression signature consistent with their ability to shuttle particles and pathogens from the airway surface to waiting immune cells.

The researchers also found a previously unknown cell type that appears to be primed by the immune molecule interferon to prevent early infection. This research could eventually lead to new treatments and vaccines for airway infections.

UTSW contributors to this study are first author Samuel Alvarez-Arguedas, Ph.D., Assistant Instructor of Internal Medicine in the Division of Infectious Diseases and Geographic Medicine; senior author Michael Shiloh, M.D., Ph.D., Professor of Internal Medicine in the Division of Infectious Diseases and Geographic Medicine and of Microbiology; Ron Mitchell, M.D., Professor of Otolaryngology-Head & Neck Surgery and Pediatrics; and John Lafin, Ph.D., Computational Biologist.

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. 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.