Developed by Arrowhead Pharmaceuticals, ARO-HIF2 is designed to selectively target HIF2α mRNA blocking the production of the HIF2α protein, showcasing a new avenue for targeted cancer therapy. The drug’s unique guidance system promotes delivery to tumor cells through an interaction with a protein (integrin αvβ3) on the surface of ccRCC cells, enhancing its uptake and therapeutic potential.

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 Simmons Cancer Center at UT Southwestern.

ccRCC is the most common type of kidney cancer in adults, characterized by the presence of clear cells in the tumor. It is a challenging disease to treat, especially in advanced stages, necessitating innovative therapeutic approaches.

The study, sponsored by Arrowhead Pharmaceuticals, enrolled 26 patients across several institutions, including at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, where the first patient enrolled, and The University of Texas MD Anderson Cancer Center. Patients with advanced ccRCC and progressive disease after typically having three or more prior therapies received ARO-HIF2 intravenously at progressively higher doses in three consecutive cohorts. ARO-HIF2 halted tumor growth in 40% of participants, and two patients achieved a partial response.

Detailed analyses in responding patients comparing pre- and post-treatment biopsies showed that HIF2α was depleted by ARO-HIF2 in the tumor. Furthermore, ARO-HIF2 suppressed tumor-produced erythropoietin, indicating effective blockade of HIF2α. 

“ARO-HIF2’s ability to target cancer cells disrupting a key tumor-driving mechanism illustrates the potential of siRNA technology in oncology,” said lead author 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 Simmons Cancer Center at UTSW.   

Nizar M. Tannir, M.D., Professor of Genitourinary Medical Oncology at MD Anderson, who co-led the study, added, “These encouraging results pave the way for further research, highlighting a novel strategy in our fight against cancer.” 

Parallel experiments in mice transplanted with a tumor sample from a biopsy of one of the responding patients in the phase one trial confirmed siRNA drug efficacy. These studies built upon preclinical studies of ARO-HIF2 through the UTSW Kidney Cancer Specialized Program of Research Excellence (SPORE), funded by the National Cancer Institute. ARO-HIF2 was first tested in mice transplanted with ccRCC patient tumors in the Brugarolas Lab. Tumors chosen for this study expressed αvβ3 on the surface and were dependent on HIF2α for their growth, as determined by sensitivity to a drug developed by the UTSW spinoff company, Peloton Therapeutics, which is now part of pharmaceutical giant Merck. These studies found that ARO-HIF2 was taken up by the transplanted tumors in mice where it depleted HIF2α, arresting ccRCC growth.

While ARO-HIF2 has shown efficacy, its development faces challenges due to neurotoxicity observed in some patients. This underscores the need for ongoing research to refine and enhance the safety profile of such innovative treatments.

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

He received research funding from Arrowhead Pharmaceuticals and has a patent and other applications pertaining to HIF2.

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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – April 03, 2024 – By focusing on a poxvirus protein, a team led by UT Southwestern Medical Center scientists has discovered an antiviral immune pathway that broadly fights a wide variety of viruses. Their findings, reported in Nature Microbiology, could eventually lead to new ways to prevent or treat viral infections or thwart autoimmune diseases.

“To learn how immune responses work, we let the viruses do the talking. This pathogen-guided approach has led us to an immune response pathway that was previously unknown,” said Don Gammon, Ph.D., Assistant Professor of Microbiology and a W.W. Caruth, Jr. Scholar in Biomedical Research at UT Southwestern. Dr. Gammon co-led this study with Emily Rex, a graduate student researcher at UTSW and former manager in the Gammon Lab.

Nearly a decade ago, when Dr. Gammon was a postdoctoral fellow under the mentorship of Nobel Laureate Craig Mello, Ph.D., at the University of Massachusetts Medical School, he and his colleagues found that viruses that don’t typically replicate in moth cells did so readily when co-infected with vaccinia virus, a poxvirus that usually infects vertebrates. Genetic manipulations showed this effect was due to a poxvirus protein called A51R, which appeared to act as an immune evasion protein that helps these viruses counter cellular antiviral defenses. It was unclear why a mammalian poxvirus protein would be capable of inhibiting antiviral responses in insect cells.

A rendering illustrates the FEAR antiviral immune pathway, which was discovered by UT Southwestern researchers and appears to work against a broad array of viruses. The image depicts cellular FACT complexes, made up of cellular proteins SSRP1 (dark blue) and Spt16 (orange). Poxvirus A51R proteins (cyan) inhibit FACT complex formation by binding to Spt16 proteins in poxvirus-infected cells.

Dr. Gammon hypothesized that poxvirus A51R proteins were likely inhibiting an antiviral defense that is common between insect and mammalian hosts. However, the nature of this antiviral response and the mechanism by which A51R blocked this response was unknown.

In the new study, Dr. Gammon, Ms. Rex, and their colleagues sought answers by searching for proteins in mammalian cells that bind to A51R. Their experiments showed A51R attached to Spt16, a protein known to join with another cellular protein (SSRP1) to form a unit called the FACT complex. Further experiments showed that when A51R was present in cells, as during a poxvirus infection, it prevented this complex from forming, blocking it from doing its job regulating gene activity by activating another protein (ETS-1) in the cell nucleus.

Although the FACT complex had never been connected to antiviral immunity, further experiments showed that the genes it regulates through ETS-1 have antiviral functions. Surprisingly, this previously unknown antiviral pathway – which the researchers named the FACT-ETS-1 Antiviral Response (FEAR) pathway – has no connection to the interferon response pathway, which was discovered in 1957 and has been thought to be the major way mammalian cells fight off viruses.

The interferon response is present only in vertebrate cells, but both the FACT complex and ETS-1-related factors are found in many organisms, including humans, bats, insects, and worms, suggesting the FEAR pathway may be evolutionarily much older than the interferon response. The FEAR pathway also appears to work against a broad array of viruses in different families, including rhabdoviruses (which cause rabies), flaviviruses (which cause Zika, dengue, and yellow fever), and orthomyxoviruses (which cause influenza).

Much remains to be learned about this newly discovered immune pathway, Dr. Gammon said, including how FEAR is activated by viruses, how other viruses inhibit it, and how it blocks viral replication at the molecular level. A deeper understanding of FEAR could lead to better vaccines, new drugs to fight viral infection, or new ways to treat autoimmune diseases if FEAR is found to be activated in these conditions, he added.

Other UTSW researchers who contributed to this study include Neal Alto, Ph.D., Professor of Microbiology; Robert Orchard, Ph.D., Assistant Professor of Immunology and Microbiology; Dustin Hancks, Ph.D., Assistant Professor of Immunology; Sruthi Chappidi, Ph.D., Computational Biologist; and graduate student researchers Dahee Seo, Aaron Embry, and Moiz Munir.

Ms. Rex is a recipient of National Institutes of Health (NIH) T32 Molecular Microbiology Training Grant funding and a Stein-Streilein Scholarship.

Dr. Alto holds the Lorraine Sulkin Schein Endowed Distinguished Professorship in Microbial Pathogenesis and is a Rita C. and William P. Clements, Jr. Scholar in Medical Research and a UT Southwestern Presidential Scholar. He is also a member of the Harold C. Simmons Comprehensive Cancer Center.

Dr. Orchard holds the Nancy Cain and Jeffery A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell. 

Dr. Gammon, shown working with Ms. Rex in the Gammon Lab, said a greater understanding of the FEAR pathway could lead to more effective vaccines and new drugs to fight viral infections.

This study was funded by the NIH (1R21AI144203-01, 1R35GM137978-01, 1R35GM142689-01, and T32 AI007520), The Welch Foundation (I-2062-20210327), and the Cancer Prevention and Research Institute of Texas (RR 170047).

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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

Nina Sanford, M.D., Assistant Professor of Radiation Oncology and Chief of Gastrointestinal Radiation Oncology Service at UT Southwestern, is a Dedman Family Scholar in Clinical Care and a member of the Harold C. Simmons Comprehensive Cancer Center.

DALLAS – March 25, 2024 – The composition of the gut microbiomes in a group of rectal cancer patients reveals distinct signatures by race, ethnicity, and age of onset, with white Hispanics showing significant presence of one specific type of bacteria, UT Southwestern Medical Center researchers report. Published in the Journal of Immunotherapy and Precision Oncology, the study provides insights that could benefit future prevention efforts or therapies for rectal and colorectal cancer that involve manipulating the microbiome.

“Our study used serial statistical methods to look at the makeup of the gut microbiome in diverse groups of patients undergoing treatment for rectal cancer, and the result suggests that the particular microbial taxa Prevotellaceae may be involved in the pathogenesis of the disease,” said Nina Sanford, M.D., Assistant Professor of Radiation Oncology and Chief of Gastrointestinal Radiation Oncology Service at UT Southwestern. Dr. Sanford co-led the study with Andrew Koh, M.D., Associate Professor of Pediatrics in the Division of Pediatric Hematology and Oncology and of Microbiology. Both are members of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

The increasing number of early-onset colorectal cancer (EOCRC) diagnoses among patients younger than age 50 has raised concerns in recent decades. About 20% of all colorectal cancer cases are now in people younger than 55, according to the American Cancer Society. Hispanic populations have been found to have a higher risk of early-age diagnosis. However, the genetic characteristics of their EOCRC tumors did not differ from those developed at a more typical age, prompting researchers to look into other factors.

Andrew Koh, M.D., Associate Professor of Pediatrics in the Division of Pediatric Hematology and Oncology and of Microbiology, is a member of the Harold C. Simmons Comprehensive Cancer Center.

In this study, UTSW researchers examined the composition and abundance of the gut microbiome in groups categorized by race, ethnicity, and age of onset to understand the potential links between microbiome signatures and diseases and treatment outcomes.

Among 64 rectal cancer patients being treated at Parkland Health and UTSW between October 2020 and August 2022, half were younger than 51, and 30 patients were Hispanic. Stool samples collected from patients were sequenced to identify microorganisms. The researchers then compared the identified microbiome across demographics such as age and race. They used multiple statistical methods to improve comparison reliability rather than the widely used single statistical method.

UTSW researchers found that white Hispanic populations had a significant enrichment of Prevotellaceae, a bacterial family known for both improved glucose metabolism as well as higher rates of inflammatory disease and chemotherapy-induced toxicity. Among Hispanics, Prevotellaceae has also been linked with higher obesity, a potential risk factor for colorectal cancers.

When comparing ages, the researchers found no common microorganisms among younger or older patients. However, younger patients had less diversity in gut microbiome compositions, which was generally linked with poorer health outcomes, the study showed.

The next step may involve experiments to assess the effect of Prevotellaceae on cancer progression. “If we identify a distinctive signature in human populations, it would be useful to investigate whether this specific microorganism directly causes the disease or changes the response to treatment,” Dr. Koh said. 

Potential therapeutic strategies for preventing or treating EOCRC in the future could include microbiome manipulation, such as dietary modifications, selective antibiotics, precision probiotics, and fecal microbiota transplant, according to the authors.

“Our study will spark the conversation about urging further exploration into the microbiome’s role in rectal cancer and its broader implications for colorectal health,” said Dr. Sanford, a Dedman Family Scholar in Clinical Care.

Other UTSW researchers who contributed to the study are David Hein, M.S., Data Scientist with the Lyda Hill Department of Bioinformatics; and Laura Coughlin, M.A., Senior Research Associate/Lab Manager, and Nicole Poulides, M.S., Research Assistant, both in the Koh Lab.

This study is supported by grants from the National Institutes of Health (K24 AI123163), the UT Southwestern and Children’s Health Pediatric Cellular and ImmunoTherapeutics Program, the Harold C. Simmons Comprehensive Cancer Center Early Onset Colorectal Cancer Pilot Funding Program, and the National Cancer Institute Cancer Center Support Grant (P30CA142543).

More information on this research, including the authors’ financial disclosures, can be found in the study.

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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

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 – March 19, 2024 – Moncrief Cancer Institute debuted its new Mobile Screening Clinic prior to the Tarrant County Commissioners Court meeting today. The $1 million, 36-foot cancer screening clinic was funded by Tarrant County through a three-year, $9 million grant awarded to Moncrief Cancer Institute in 2022. Part of the federal funding Tarrant County received through the American Rescue Plan Act (ARPA), the grant enabled Moncrief to expand its comprehensive cancer screening program to more underserved residents in Tarrant County.

Keith Argenbright, M.D., is Director of the Moncrief Cancer Institute and Professor in the Harold C. Simmons Comprehensive Cancer Center and Peter O'Donnell Jr. School of Public Health at UT Southwestern.

“The pandemic caused disruptions in cancer screenings, and through this grant, we’ve been working to avoid a post-pandemic cancer crisis in Tarrant County by providing free cancer screening services to our most vulnerable residents,” said Keith Argenbright, M.D., Director of the Moncrief Cancer Institute and Professor in the Harold C. Simmons Comprehensive Cancer Center and Peter O’Donnell Jr. School of Public Health at UT Southwestern Medical Center. “In two years, we’ve screened nearly 10,000 residents for breast, cervical, colorectal, lung, and prostate cancer, with many of these patients being screened on our first Mobile Screening Clinic. By adding this second Mobile Screening Clinic, we can double our screening efforts in Tarrant County for breast cancer and prostate cancer, the most common cancers among women and men. We’re tremendously grateful for the opportunity to partner with the Commissioners Court to have an even larger impact on the health of our community.” 

Over half a million new cases of breast cancer and prostate cancer are expected to be diagnosed in the U.S. this year, according to the American Cancer Society. These cancers have a high cure rate when they are caught early, and screening is the key to early detection, Dr. Argenbright said. Eligible residents in Tarrant County can receive free breast cancer and prostate cancer screenings on Moncrief’s new Mobile Screening Clinic, which is ADA-accessible and equipped with the latest medical technologies, including digital 3D mammography and high-speed telemedicine links to cancer experts.

Moncrief Cancer Institute's new Mobile Screening Clinic will provide cancer screening services to eligible residents in Tarrant County. (Photo credit: Moncrief Cancer Institute)

“The Moncrief Cancer Institute’s Mobile Screening Clinic will bring cancer screening services directly into communities that need it the most and provide a proactive measure to combat cancer in Tarrant County,” Tarrant County Judge Tim O’Hare said. “The Mobile Screening Clinic will ultimately save lives and improve outcomes through early detection and intervention. This strategic investment made by the prior Tarrant County Commissioners Court, through American Rescue Plan funding, represents a long-term commitment to the well-being of the residents of Tarrant County.”

The new Mobile Screening Clinic is equipped with the latest medical technologies, including digital 3D mammography.
(Photo credit: Moncrief Cancer Institute)

“I have enjoyed a long partnership with the Moncrief Cancer Institute around the disparate impact of prostate cancer on the African American community,” Tarrant County Precinct 1 Commissioner Roy Charles Brooks said. “When the opportunity presented itself to expand throughout Tarrant County with the programs, procedures, and screening procedures we had developed over the years, I thought this was an outstanding use of ARPA dollars.”

About Moncrief Cancer Institute

Moncrief Cancer Institute is a nonprofit, community-based early detection and support center and part of the Simmons Cancer Center, the first and only National Cancer Institute-designated Comprehensive Cancer Center in North Texas. Moncrief Cancer Institute offers an exceptional level of academic medical expertise in cancer services. 

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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – March 15, 2024 – At exactly 11 a.m. Friday, surrounded by family, friends, and mentors, 224 members of UT Southwestern Medical School’s Class of 2024 – who all embarked on their medical education during the height of the COVID-19 pandemic – learned where they will continue their training.

As the students opened their envelopes, revealing which residency programs they had matched with in Texas and across the country, anticipation bubbled over into pure joy, and Match Day cheers echoed throughout UTSW’s Bryan Williams, M.D., Student Center gymnasium.

UTSW students are headed to more than 85 residency programs from coast to coast, including Johns Hopkins, Massachusetts General, and the University of California-San Francisco, and more than 90 matched to Texas programs, including 53 at UTSW.

In all, more than 100 matched to hospitals affiliated with U.S. News & World Report’s top 25 medical schools, which include UTSW.

“Match Day is an emotional, momentous day for our students, who have worked earnestly toward their dreams over these past four years,” said Angela Mihalic, M.D., Dean of Medical Students and Associate Dean for Student Affairs at UT Southwestern Medical School, Professor of Pediatrics, and a Distinguished Teaching Professor at UT Southwestern Medical Center. “Despite a challenging start with a completely virtual curriculum during their first year due to the pandemic, members of the Class of 2024 have received outstanding clinical training and are well prepared for the next step in their medical education. Not only is this a milestone moment for our students, but also a reminder of our country’s critical need for more highly trained physicians for primary and specialty care.” 

The students, who will graduate in May, were among about 41,000 future physicians nationwide who opened their envelopes simultaneously as part of the National Resident Matching Program.

Top specialty selections for UT Southwestern students included internal medicine, pediatrics, psychiatry, anesthesiology, family medicine, emergency medicine, neurology, orthopedics, and surgery. Matches ranged from medical centers in New York to California, Florida to Washington state.

“While a top-notch training environment and exposure to cutting-edge medicine were certainly expected, how I was treated from the moment I stepped onto campus made an even bigger impact on my decision,” said Nicholas Sevey, who grew up in a family of nurses in Coahoma, Texas, and is pursuing a career in Med-Peds (internal medicine-pediatrics). “I felt welcomed, wanted, and supported by everyone. UTSW immediately felt like a place where I could grow into the physician I wanted to be. Four years later, I still believe it was the best decision I ever made.”

Vanessa Ramirez-Allen, who grew up in Houston, decided to pursue medicine after a career in the tech industry. She plans to specialize in anesthesiology.

“I chose UT Southwestern for medical school because I wanted to start my training at an institution that would provide the broadest exposure possible,” she said.  “UTSW has high volumes and diverse patient cases across all specialties and provides countless opportunities for research, advocacy, and community service.”

UTSW training opportunities, rankings, accolades

UT Southwestern’s training facilities include  William P. Clements Jr. University Hospital, ranked by U.S. News as the No. 1 hospital in Texas (tied) and one of the top 22 hospitals nationwide; Parkland Memorial Hospital, one of the nation’s busiest public hospitals; and Children’s Health Dallas, one of the nation’s largest children’s hospitals. 

UT Southwestern also boasts a 49,000-square-foot Simulation Center – one of the largest of its kind in the nation.

Additionally, UT Southwestern is ranked by U.S. News among the top hospitals in the nation in 11 specialties, including Rehabilitation; Pulmonology and Lung Surgery; Diabetes and Endocrinology; Neurology and Neurosurgery; Cancer; Cardiology, Heart, and Vascular Surgery; Geriatrics; Urology; Otolaryngology; Gastroenterology and GI Surgery; and Obstetrics and Gynecology.

Other key distinctions 

• UT Southwestern is listed among the top 5% of hospitals nationally for patient satisfaction and is rated “excellent” for patient experience and patient services in areas including Cancer; Cardiology and Heart Surgery; Diabetes and Endocrinology; Ear, Nose, and Throat; Gastroenterology and GI Surgery; Geriatrics; Neurology and Neurosurgery; Obstetrics and Gynecology; Orthopedics; Pulmonary and Lung Surgery; and Urology.

• UTSW’s  Harold C. Simmons Comprehensive Cancer Center  is the only National Cancer Institute-designated comprehensive cancer center in the region – one of 56 in the United States, placing it among the top 4% of the approximately 1,500 cancer centers in the nation.

• UTSW is designated an Advanced Comprehensive Stroke Center by The Joint Commission and the American Heart Association/American Stroke Association and has one of the nation’s leading epilepsy clinics – a Level 4 center, the highest possible rating by the National Association of Epilepsy Centers – as part of the Peter O’Donnell Jr. Brain Institute.

• UTSW has more than 5,800 research projects fueled by nearly $719 million in funding and ample opportunities to participate in research, including a Scholarly Activity period with multiple research tracks available and more than 450 labs on campus.

• The Perot Family Scholars Medical Scientist Training Program, one of just 54 M.D./Ph.D. training programs in the country supported by the National Institutes of Health (NIH), offers a dual degree to strengthen the advancement of laboratory discoveries into the clinical arena.

• UTSW ranks No. 3 in the  2023 Nature Index among global health care institutions for its published research.

• UT Southwestern Medical School  is ranked nationally by U.S. News among the “Best Graduate Schools,” and the Medical Center has nationally rated programs in its Graduate School of Biomedical Sciences.

• The new Peter O’Donnell Jr. School of Public Health, which welcomed its inaugural class last fall, is accepting applications for its M.P.H. and Ph.D. programs for Fall 2024.

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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – March 13, 2024 – Delivering genetic material tagged with a cellular “ZIP code” prompted cells to secrete proteins or drugs into the bloodstream that successfully treated psoriasis and cancer in mouse models, UT Southwestern Medical Center scientists report in a new study. The findings, published in PNAS, could eventually lead to new therapies in which patients’ bodies produce their own drugs, avoiding the drawbacks of many intravenously administered medicines.

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

“Instead of going to the hospital or outpatient clinic frequently for infusions, this technology may someday allow a patient to receive a treatment at a pharmacy or even at home once a month, which would be a significant boost to their quality of life,” said study leader Daniel Siegwart, Ph.D., Professor of Biomedical Engineering and Biochemistry and co-leader of the Chemistry and Cancer Research Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

In 2020, researchers elsewhere developed a new type of vaccine that relies on messenger RNA (mRNA) – a single-stranded genetic molecule that cells use to produce a specific protein – to prompt an immune reaction against the virus that causes COVID-19. Billions of doses of these vaccines have been delivered successfully to people around the world with few side effects.

This effort is far from the first time that scientists have used genetic medicines – therapies in which genetic material is delivered to cells to produce a protein to replace one that’s missing or defective. Gene therapies are currently being investigated or used for dozens of diseases. However, Dr. Siegwart explained, the proteins produced by genetic medicines generally stay trapped inside cells. Because autoimmune and many other diseases cause systemic effects, inducing cells to secrete therapeutic proteins into the bloodstream could relieve symptoms throughout the body.

Toward this goal, Dr. Siegwart and his colleagues looked to signal peptides (SPs), genetic sequences that serve as cellular “ZIP codes” to direct proteins produced from genetic material to where they are needed. Although most known SPs direct proteins to organelles within cells, some – called secretory SPs – cause proteins to be secreted from cells into systemic circulation.

Dr. Siegwart and his colleagues isolated a piece of mRNA that produces secretory SP derived from a protein called Factor VII that is involved in blood clotting. Next, they attached this SP-encoding mRNA fragment to four different mRNA sequences that produced various proteins: a fluorescent protein called mCherry that could provide a visual readout on whether it was secreted from cells; a human protein involved in blood production called erythropoietin; a therapeutic protein called etanercept used to treat inflammatory diseases; and another therapeutic protein called anti-PD-L1 used to treat cancer. They then packaged these modified mRNAs into lipid nanoparticles and delivered them to cells growing in laboratory dishes. Their results showed that the cells secreted SP-tagged proteins made from these mRNAs into the surrounding liquid, whereas the proteins without the secretory SP remained inside cells that received mRNAs.

This observation inspired the researchers to examine whether the body could serve as a biofactory to produce and secrete therapeutic proteins. Indeed, when the researchers treated mice with psoriasis with the modified mRNA coding for etanercept, the psoriasis plaques in their skin were significantly decreased, as were molecular markers for inflammation. Similarly, when the researchers treated mice bearing two types of cancer with modified mRNAs coding for anti-PD-L1, tumor growth was significantly decreased, and the mice survived twice as long as those that were not treated.

Dr. Siegwart noted that using the body’s own machinery to make and deliver therapeutic proteins may help to overcome side effects and increase the efficacy of protein drugs that currently must be delivered by infusion. It could also decrease the hassle of having to receive frequent and sometimes lengthy infusions. Using this technology to produce these drugs within the body could eventually improve health and quality of life for patients with inflammatory diseases, cancers, clotting disorders, diabetes, and a range of genetic disorders, he said.

Other UTSW researchers who contributed to this study are Lukas Farbiak, Ph.D., Assistant Professor of Biomedical Engineering; Richard C. Wang, M.D., Ph.D., Associate Professor of Dermatology; graduate student researchers Amogh Vaidya, Erick Guerrero, Joshua Robinson, and William E. Miller; senior research associates Eunice E. Lee, B.S., and Xu Wang, Ph.D.; resident Elysha K. Rose, M.D.; and postdoctoral researcher Xizhen Lian, Ph.D.

This study was funded in part by a National Institutes of Health National Institute of Biomedical Imaging and Bioengineering grant (R01 EB025192-01A1) and the National Cancer Institute Cancer Center Support Grant (P30CA142543).

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

The University of Texas has filed patent applications related to the technology involved in this study that has been licensed to Signify Bio. More information, including author financial disclosures, can be found in the manuscript.

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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – March 11, 2024 – A molecule has demonstrated its ability to kill tumor cells and incite an immune response in preclinical models of small cell lung cancer (SCLC), according to UT Southwestern Medical Center researchers. The findings, published in Nature Communications, could lead to more successful treatments for SCLC, one of the leading causes of cancer-related deaths in the U.S.

Esra A. Akbay, Ph.D., Assistant Professor of Pathology, is a member of the Development and Cancer Research Program of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“We have a really exciting new drug that could target a disease that’s very difficult to treat,” said Esra A. Akbay, Ph.D., Assistant Professor of Pathology and a member of the Development and Cancer Research Program of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “This research marks a crucial step toward potentially reshaping the standard of care for small cell lung cancer patients.”

With more than 32,000 new cases expected to be diagnosed in the U.S. in 2024, SCLC is a particularly lethal cancer with limited effective treatment options. While SCLC tumors may initially respond to therapeutics, they’re highly metastatic and tend to develop treatment resistance. They’re also successful at concealing themselves from the body’s immune system.

Scientists believe that treatment resistance is tied, in part, to the abundance of cancer-initiating cells (CICs) in these tumors that, in turn, increase the total number of SCLC cells and drive their migration and spread to other organs. CICs produce telomerase, an enzyme that preserves telomeres, which are the protective caps at the end of DNA sequences. Normal cells die or senesce as their telomeres shorten over time. In cancer cells, however, the telomerase enzyme helps cancer cells maintain their telomeres, live longer, and metastasize. 

Dr. Akbay and her team devised a series of tests using the telomere-targeting molecule 6-thio-2’-deoxyguanosine (6-thio-dG). After entering the bloodstream, 6-thio-dG is rapidly incorporated into tumor cells where it damages telomeres and causes cell death while at the same time sparing healthy cells.  

“It’s difficult to devise treatments that affect cancer cell DNA because most of the time they’re also toxic to bone marrow cells, which produce immune and blood cells,” Dr. Akbay explained. “But 6-thio-dG is nontoxic to healthy cells in therapeutic doses.”

Dr. Akbay’s team tested the efficacy of 6-thio-dG both in vitro and in mouse models and found that it inhibits the growth of SCLC cells, even those resistant to chemotherapy. 

The drug also had positive effects on the tumor immune environment. Researchers found that 6-thio-dG makes SCLC in mice more visible to the immune system. It increased recruitment of T cells and natural killer cells and decreased the presence of myeloid cells that can promote tumor growth. In mice with intact immune systems, they found that 6-thio-dG can sensitize SCLC cells to radiation treatment.

Other UTSW researchers who contributed to this study are co-first authors Buse Eglenen-Polat, M.D., and Ryan R. Kowash, B.S., with the Akbay Lab; John D. Minna, M.D., Director of the Hamon Center for Therapeutic Oncology Research and Professor of Internal Medicine and Pharmacology; Jerry W. Shay, Ph.D., Professor of Cell Biology; Prithvi Raj, Ph.D., Associate Professor of Immunology and Director of the Microbiome Research Lab; Benjamin J. Drapkin, M.D., Ph.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology; Lin Xu, Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health and Pediatrics; Akbay Lab members Mingrui Zhu, Ph.D., Hai-Cheng Huang, M.D., who is a Ph.D. candidate, and Matthew Bender, B.S.; Shay Lab member Silvia Siteni, Ph.D.; Minna Lab member Victor Stastny, B.S.; and Kenian Chen, Ph.D., Computational Biologist in the Quantitative Biomedical Research Center. 

Drs. Akbay, Drapkin, Minna, Shay, and Xu are also members of Simmons Cancer Center.

Dr. Akbay is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research. Dr. Minna holds the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology and the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research. Dr. Shay is a Distinguished Teaching Professor and holds The Southland Financial Corporation Distinguished Chair in Geriatrics.

This study was supported by a CPRIT Scholar Award (RR160080), National Institutes of Health grant (R01CA276058), National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543), a U.S. Department of Defense grant (W81XWH-21-1-0856), The Welch Foundation (1975-20190330), A Breath of Hope Lung Foundation Fellowship Award (ABOHLF 2020), American Cancer Society Research Scholar Grant (RSG-22-051-01-IBCD), a Mary Kay Ash Foundation grant, NCI Specialized Programs of Research Excellence (SPORE) in Lung Cancer (5P50CA070907), the World Brain Microscopy Core Facility for slide scanning (RRID: SCR_017949); CPRIT Core Facility Support Award (RP180770), and grants U01CA213338 and 5T32CA124334.

MAIA Biotechnology Inc. is developing and commercializing the telomere-targeting agent 6-thio-dG, which has been granted orphan drug designation by the U.S. Food and Drug Administration for SCLC. Dr. Shay is a scientific adviser for MAIA Biotechnology. Drs. Siteni and Shay are named inventors on patents licensed to MAIA Biotechnology (16/450,430; 62/636,775; 62/646,820; 16/304,538; 17/200,539; 63/388,688). Dr. Minna receives licensing fees from the National Cancer Institute and UT Southwestern to distribute cell lines. 

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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – March 04, 2024 – Nine scientists and physicians in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center have been awarded nearly $13 million in grants from the Cancer Prevention and Research Institute of Texas (CPRIT) to support research and prevention efforts on a wide range of cancer issues.

“This latest round of CPRIT funding will lead the way to discoveries that advance our understanding of cancer and to better care for cancer patients in Texas and beyond,” said Carlos L. Arteaga, M.D., Professor and Director of the Simmons Cancer Center and Associate Dean of Oncology Programs at UT Southwestern.

These annual grants bring the total that UT Southwestern has been awarded from CPRIT for academic research and prevention to more than $362 million since 2010.

UT Southwestern also was awarded two recruitment grants totaling $6 million this year to attract two high-profile cancer researchers to Texas.

John Abrams, Ph.D., Professor of Cell Biology, was awarded $1,039,356 to test whether the loss of a tumor suppressor gene known as p53 drives cancers by reactivating mobile elements called retrotransposons. The research would also examine a conditional cancer-prone platform to define the mechanism by which p53 silences the mobile elements.

Keith E. Argenbright, M.D., Director of UTSW’s Moncrief Cancer Institute in Fort Worth and Professor of Family and Community Medicine and in the Peter O’Donnell Jr. School of Public Health, was awarded $2,487,342 to increase access to a large-scale colorectal cancer (CRC) screening program for rural and medically underserved populations across 67 counties, reduce existing disparities, and improve CRC-related health outcomes in these communities through public education, outreach, and navigation for follow-up services.

Jef De Brabander, Ph.D., Professor of Biochemistry, was awarded $1,049,754 to test a novel molecule known as MM017 that shares characteristics with a drug currently used in colorectal cancer treatment called oxaliplatin. The drug works by blocking ribosome biogenesis. The research would investigate more specific and targeted inhibitors of ribosome biogenesis that might be better tolerated among patients with colorectal cancer.

Raquibul Hannan, M.D., Ph.D., Professor of Radiation Oncology as well as Immunology and Urology and Chief of Genitourinary Radiation Oncology Service, and his team of investigators from the Kidney Cancer Program were awarded $1,999,993 to conduct a clinical trial, which is also supported by the Kidney Cancer SPORE grant, to evaluate the impact of stereotactic ablative body radiotherapy combined with a novel drug called IMSA101 to harness the immune system in patients with metastatic kidney cancer.

Gerta Hoxhaj, Ph.D., Assistant Professor in Children’s Medical Center Research Institute at UT Southwestern as well as Biochemistry and Pediatrics, was awarded $1,050,000 to advance the understanding of the metabolic functions of NADK2, an enzyme amplified in lung cancer cells. Research has already shown that without NADK2, lung cancer cells cannot produce an amino acid called proline needed for them to grow. The next step is to determine whether targeting NADK2 could be an effective way to treat lung cancer.

Lee Kraus, Ph.D., Professor and Director of the Cecil H. and Ida Green Center for Reproductive Biology Sciences, Professor of Obstetrics and Gynecology and Pharmacology, and Assistant Dean for Research Development, was awarded $1,049,743 to study the molecular underpinnings of ovarian cancer. The proposal aims to discover new insights for the use of PARP-16 inhibitors in cancers with enhanced PARP-16 activity.

Shuang Liang, Ph.D., Assistant Professor of Immunology, was awarded $1,049,997 to study molecular mechanisms to advance the understanding of how obesity promotes chronic liver inflammation, which is strongly associated with hepatocellular carcinoma. The answers could guide the development of new preventive strategies and early detection methods to alleviate the burden of liver cancer in people who are obese.

Asal Rahimi, M.D., Associate Professor of Radiation Oncology, Associate Vice Chair for Program Development, Medical Director of the Simmons Cancer Center Clinical Research Office, and Chief of Breast Radiation Oncology Service, was awarded $1,999,963 to conduct a clinical trial using a preoperative ablative radiation approach for patients with early-stage breast cancer that could potentially eliminate surgery. The research will include preoperative stereotactic ablative radiation therapy followed by evaluations using a microbubble contrast-enhanced ultrasound and optoacoustic ultrasound imaging.

Qing Zhang, Ph.D., Associate Professor of Pathology, was awarded $1,049,997 to study a pathway called JMJD6-DGAT1 that may contribute to tumor formation in clear cell renal cell carcinoma and investigate a specific DGAT1 inhibitor as a way to slow tumor growth and eliminate metastasis.

Dr. Arteaga holds the Annette Simmons Distinguished University Chair in Breast Cancer Research. Dr. Kraus holds the Cecil H. and Ida Green Distinguished Chair in Reproductive Biology 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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Feb. 27, 2024 – A subpopulation of gut bacteria given a commonly used antibiotic became “persisters” that were able to survive without developing true resistance, UT Southwestern Medical Center scientists discovered. Their findings, published in Cell Host & Microbe, could lead to better ways to fight bacterial infections.

Andrew Koh, M.D., Associate Professor of Pediatrics and Microbiology at UT Southwestern, is a member of the Harold C. Simmons Comprehensive Cancer Center.

“Researchers had hypothesized the existence of these persistent bacteria based on petri dish experiments, but to observe them developing in a living host has never been done,” said Andrew Koh, M.D., Associate Professor of Pediatrics and Microbiology. Dr. Koh co-led the study with Erdal Toprak, Ph.D., Associate Professor of Pharmacology and in the Lyda Hill Department of Bioinformatics. Both are members of the Harold C. Simmons Comprehensive Cancer Center.

Antibiotic resistance is one of modern medicine’s most pressing crises, explained Dr. Koh, with an estimated 2.8 million antibiotic-resistant infections resulting in more than 35,000 deaths a year in the U.S. But how antibiotic resistance develops – particularly within live animal hosts – is unclear. One reason for this is that mice, the quintessential lab model, efficiently clear several antibiotics delivered over set time periods, the way most human patients receive these drugs, causing a mismatch between antibiotic concentrations in mice and humans.

Hoping to observe antibiotic resistance forming in live mice, the researchers developed a mouse model in which antibiotics were delivered continuously through a programmable subcutaneous pump, allowing their serum antibiotic concentrations to remain stable as long as the pump stayed on.

Erdal Toprak, Ph.D., Associate Professor of Pharmacology and in the Lyda Hill Department of Bioinformatics at UT Southwestern, is a member of the Harold C. Simmons Comprehensive Cancer Center and a Southwestern Medical Foundation Scholar in Biomedical Research.

Working with Escherichia coli – a common species of gut bacteria – introduced to “germ-free” mice that didn’t have a natural microbiome, the researchers found that most bacteria were killed by the antibiotic, cefepime. But some of these microbes survived inside intestinal cells and took longer to die when treated with additional antibiotic in petri dishes compared with E. coli isolated from untreated mice.

Genetic analysis showed these persistent bacteria had lost function of a gene called wbaP, which plays an important role in creating a protective coating on the surface of E. coli and some other bacteria species. This loss appeared to be key in allowing the persistent bacteria to invade intestinal cells, where the antibiotic concentration was nearly 20 times lower inside than outside, and in slowing the bacteria’s deaths upon exposure to high antibiotic concentrations.

Such persisters could be the reason why antibiotics sometimes don’t completely clear infections, allowing dangerous antibiotic resistance to develop – a scenario Drs. Toprak and Koh and their colleagues plan to investigate in future studies. The innovative model they developed could be used to examine a variety of questions related to antibiotic resistance in living animals, they added, including whether certain foods, commensal bacteria, other drugs, or autoimmune conditions can affect bacterial survival and resistance upon antibiotic exposure.

Dr. Koh, a physician-scientist, and Dr. Toprak, an experimental biophysicist, noted that their collaboration is a testament to the collegial environment at UTSW, which encourages interdisciplinary partnerships.

“This initiative exemplifies how complex global challenges can be addressed more effectively by uniting diverse scientific fields,” said Dr. Toprak, a Southwestern Medical Foundation Scholar in Biomedical Research.

Other UTSW researchers who contributed to this study include Lora V. Hooper, Ph.D., Chair and Professor of Immunology and Professor of Microbiology and in the Center for the Genetics of Host Defense; Noelle S. Williams, Ph.D., Professor of Biochemistry; Xiaowei Zhan, Ph.D., Associate Professor in the Peter O’Donnell Jr. School of Public Health and the Center for the Genetics of Host Defense; Laura Filkins, Ph.D., Assistant Professor of Pathology; Parastoo Sabaeifard, Ph.D., Senior Research Scientist; Muhammed Sadik Yildiz, Ph.D., postdoctoral researcher; Adam Lyon, graduate student researcher; Laura Coughlin, M.A., Senior Research Associate/Lab Manager; Nicole Poulides, M.S., Research Assistant; Ahmet C. Toprak, medical student; Cassie Behrendt, Research Technician; Xiaoyu Wang, Ph.D., Research Scientist; Marguerite Monogue, Pharm.D., Clinical Pharmacist Specialist; Jiwoong Kim, M.S., Computational Biologist; and Shuheng Gan, M.S., Computational Biologist.

Dr. Hooper holds the Jonathan W. Uhr, M.D., Distinguished Chair in Immunology and is a Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell. She also is a member of the National Academy of Sciences and a Howard Hughes Medical Institute Investigator.

This study is supported by grants from the National Institutes of Health (K24-AI123163, R01-GM125748, DOD-PR172118, and R01-DK070855), Human Frontiers Science Program Research (RGP0042/2013), The Welch Foundation (I-208-220210327 and I-1874), the Howard Hughes Medical Institute, the UT Southwestern and Children’s Health Cellular and ImmunoTherapeutics Program, and the UTSW Endowed Scholars 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 25 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

Daolin Tang, M.D., Ph.D., is Professor of Surgery and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“Our study is the first to report a cancer cell-specific induction of ferroptosis,” said Daolin Tang, M.D., Ph.D., Professor of Surgery at UT Southwestern, who co-led the study with Rui Kang, M.D., Ph.D., Associate Professor of Surgery at UT Southwestern. Drs. Tang and Kang are members of the Harold C. Simmons Comprehensive Cancer Center.

Just over a decade ago, researchers elsewhere discovered ferroptosis, a type of cell death characterized by an accumulation of large amounts of iron and uncontrolled lipid peroxidation. Because some types of cancer develop resistance to chemotherapy drugs, finding ways to prompt ferroptosis quickly became the focus of significant cancer research, Dr. Tang explained.

Most of these efforts focused on inhibiting an antioxidant enzyme called GPX4, a master repressor of ferroptosis. However, Dr. Tang said, GPX4-inhibiting compounds identified thus far not only induced ferroptosis in cancer cells but also in a variety of immune cell types – causing side effects in lab animals while also hindering the immune system’s natural anti-cancer response.

Rui Kang, M.D., Ph.D., is Associate Professor of Surgery and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Searching for a compound that targets GPX4 only in cancer cells, Drs. Tang and Kang and their colleagues screened more than 4,200 compounds from a pharmaceutical company’s drug library, dosing human pancreatic cancer cells growing in petri dishes. These experiments found that a compound called N6F11 not only reduced the amount of GPX4 present in cells, but also readily caused these cells to die from ferroptosis. Nearly half of the cells were dead within 12 hours. The researchers had similar results when they dosed other cancer cell types, including bladder, breast, and cervical, with N6F11.

Additional experiments showed that N6F11 binds to another protein called TRIM25, which regulates the amount of GPX4 and other proteins and is especially abundant in cancer cells. That binding prompts TRIM25 to tag GPX4 with ubiquitin, a protein that directs GPX4 to cellular garbage dumps where it’s degraded. With GPX4 gone, cells die from ferroptosis.

UT Southwestern researchers have found a compound called N6F11 that triggers selective induction of ferroptosis in cancer cells to suppress pancreatic tumor growth.

Further testing on mouse models with pancreatic cancer showed N6F11 not only virtually stopped cancer progression, Dr. Tang said, but it also appeared to be nontoxic for healthy tissues or cells. The immune-inhibiting side effects seen in previous research focused on inhibiting GPX4 were absent with N6F11. In the next phase, researchers gave animals a combination of N6F11 and a cancer treatment known as an immune checkpoint inhibitor that is commonly used in patients. This combination significantly improved their survival rates compared to mice that received either treatment separately.

Future research will focus on developing N6F11 into a viable drug – a process that could take several years – as well as searching drugs already approved by the U.S. Food and Drug Administration for those that act similarly to N6F11, which would require less time and money, Dr. Tang said.

Other UTSW researchers who contributed to this study are Zhuan Zhou, Ph.D., Assistant Professor of Dermatology, and Chunhua Yu, M.D., Ph.D., Manager of the Tang Lab.

This study was funded by National Institutes of Health grants (R01CA160417, R01CA229275, and R01CA211070). 

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, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

Daniel Siegwart, Ph.D., is Director of the Program in Genetic Drug Engineering, Professor of Biomedical Engineering and Biochemistry, and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“This collaboration, leveraging transformative chemistry and engineering contributions from Pfizer and UT Southwestern, will advance our fundamental understanding of genetic medicines, expand the use of artificial intelligence (AI) design methodologies, and lead to the development of new delivery technologies for the creation of potential therapies,” said the project's Principal Investigator Daniel Siegwart, Ph.D., Director of the Program in Genetic Drug Engineering, Professor of Biomedical Engineering and Biochemistry, and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

This agreement will further UT Southwestern’s research and development of cell-targeted nucleic acid and gene editing therapies that Pfizer may apply to its portfolio of investigational programs. 

“Collaborations and partnerships are key to further build Pfizer’s successful portfolio into RNA-based medicines through the development of new technologies and strategies,” said David Morrissey, head of Pfizer’s RNA Accelerator. “RNA-based platforms enable genetically driven medicines, and we are looking forward to working together with the UTSW team to explore new delivery systems and therapeutic applications. The UTSW capabilities can help accelerate our RNA medicines portfolio, paving the way for groundbreaking advancements in health care.”

The joint effort will bring together UTSW’s recent advances in understanding RNA-based biology and improved delivery systems for RNA-based therapies with Pfizer’s robust and extensive RNA knowledge, rapid manufacturing capabilities, and scientific innovation. It has the potential to propel the concept of genetic medicines forward into new therapeutic areas.

The Siegwart Lab has worked for more than a decade on developing lipid nanoparticles (LNPs) for the delivery of mRNA, siRNA, genome editors, and other genetic drugs. Dr. Siegwart was an early pioneer in the development of delivery systems for genome editing, reporting the first-ever in vivo CRISPR/Cas edit using synthetic nanoparticles in December 2016. More recently, his team solved a major challenge in nucleic acid delivery, reporting the first predictable system for delivery of mRNA and genome editors outside of the liver, providing a potential path for new lung- and spleen-targeted therapies. 

Dr. Siegwart holds the W. Ray Wallace Distinguished Chair in Molecular Oncology 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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Feb. 01, 2024 – Nutritious meal kits and no-prep meals improved food security and perceived dietary quality among clients of a Dallas food pantry, according to a pilot study led by UT Southwestern Medical Center. Published in BMC Public Health, the research suggested these dietary interventions could also help with prevention or management of diet-related chronic diseases.

Kelseanna Hollis-Hansen, Ph.D., is Assistant Professor in the Peter O'Donnell Jr. School of Public Health and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

“When people are food secure and able to eat a more balanced diet with greater variety and nutritious options, they are less likely to miss school, are able to be more engaged at work, and can improve their overall health and well-being,” said first author Kelseanna Hollis-Hansen, Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “Understanding what nutrition interventions can be implemented through trusted community partners and which options are most desirable to the community members themselves can encourage engagement and lead to greater improvements in food security and diet quality.”

Food pantry clients tend to experience higher rates of food insecurity and diet-related illness, including heart disease, stroke, hypertension, high cholesterol, and Type 2 diabetes. Some face additional barriers, such as disabilities or prohibitively high costs of nutritious foods. Of the tens of thousands of annual clients served through Dallas’ Crossroads Community Services, 91% consistently lack access to nutritious food, and few consume the minimum recommended amounts of fruits or vegetables.

UTSW researchers partnered with Crossroads to learn more about clients’ preferences for nutritious no-prep meals and meal kits and whether those interventions could improve food security and diet quality. Previous research has shown that meal kits, which supply ingredients and a recipe for clients to follow, lead to more selections of produce and whole grains from the food pantry than other options. Nutritious no-prep meals, which need only to be reheated, are another nutrition intervention strategy that could remove challenges that some people might face with food preparation.   

The ingredients for each meal kit are packed in a bag that has the recipe attached for food pantry clients to use.

“Being able to deliver these interventions through a trusted community partner that people already visit reduces the number of places they have to go to fill their fridge and pantry, and it invests back into the community,” Dr. Hollis-Hansen said.

Sixty-six Crossroads clients were randomly assigned either meal kits or no-prep meals – breakfasts and dinners for a family of three – for two weeks. Favorite breakfast entrees included blueberry waffles, a spinach and mozzarella flatbread, and a turkey sausage burrito. Dinner options included chicken teriyaki with brown rice and carrots; chimichurri beef with carrots, cauliflower, and couscous; and Dijon pulled pork with green peas, carrots, and quinoa.

"We want to understand what nutrition interventions and types of food are most desirable to these community members so that we can provide more of what people actually want to eat at Crossroads,” Dr. Hollis-Hansen noted. 

On average, participants had an annual household income of $19,058, and 47% did not have medical insurance.

From surveys, UTSW researchers found that both meal options improved participants’ food security and perceived diet quality. Participants, who completed questionnaires at the outset of the study and after two weeks, liked both options but favored the meal kits more over time. Further research on improving healthy no-prep meals could benefit different populations, such as people who have recently had surgery or are receiving medical treatments.

Other UTSW researchers who contributed to this study are lead author Sandi Pruitt, Ph.D., Associate Professor in the O’Donnell School of Public Health and Associate Director of Community Outreach, Engagement, and Equity in the Simmons Cancer Center; Michael E. Bowen, M.D., Associate Professor of Internal Medicine in the Division of General Internal Medicine, Pediatrics, and the O’Donnell School of Public Health and a member of the Simmons Cancer Center; and Jaclyn Albin, M.D., Associate Professor of Pediatrics and Internal Medicine and Director of Culinary Medicine at UTSW. Other contributors from the O’Donnell School of Public Health are Tammy Leonard, Ph.D., Professor; MinJae Lee, Ph.D., Associate Professor; Carolyn Haskins, M.S., Project Coordinator; and Jessica Turcios, B.S., Senior Research Assistant. 

Drs. Lee, Leonard, and Pruitt are also members of the Simmons Cancer Center. Dr. Bowen is a Dedman Family Scholar in Clinical Care.

This work is supported by the UT Southwestern Medical Center Program for the Evaluation and Development of Model Community Health Initiatives Community-Based Research Award and the National Center for Advancing Translational Sciences under a supplement of award UL1TR003163.

Drs. Pruitt and Leonard have personal consulting relationships with Crossroads Community Services.

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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Jan. 16, 2024 – By taking advantage of mechanisms that allow cancer cells to evade immune attack, UT Southwestern Medical Center researchers have developed a new strategy in animal models that has potential for treating ulcerative colitis. Their findings, reported in Nature Biomedical Engineering, could eventually provide relief to millions of people worldwide who have this or other autoimmune conditions.

“We’re borrowing something that cancer uses for evil and making it into something good,” said senior author Andrew Wang, M.D., Professor and Vice Chair of Translational Research and Commercialization in the Department of Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Wang co-led the study with first author Kin Man Au, Ph.D., Assistant Professor of Radiation Oncology.

Andrew Wang, M.D., Professor and Vice Chair of Translational Research and Commercialization in the Department of Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, holds the A. Kenneth Pye Professorship in Cancer Research.

For decades, Dr. Wang explained, researchers have known that the immune system can recognize and kill cancers, keeping most malignancies in check. However, cancers can develop the ability to escape the immune system, producing proteins in their microenvironment that suppress immune cell activity and allow tumors to flourish. Conversely, autoimmune conditions develop when the immune system mistakes healthy cells as foreign invaders and launches unnecessary immune attacks.

Dr. Wang and his colleagues realized that they could take a page from cancer’s playbook, retraining the immune system to suppress its activity against specific cell types attacked in autoimmune diseases. Previous studies have used this approach in animal models of Type 1 diabetes and multiple sclerosis.

This latest study focuses on ulcerative colitis, a chronic disease characterized by an autoimmune attack against colon cells. For this and other autoimmune diseases, there is no cure. These conditions are typically treated with systemic immunosuppressors, which can reduce inappropriate immune activity. But they have long-term health complications, including an increased risk of infections and cancer.

The researchers worked with a well-established mouse model of ulcerative colitis that mimics the heavy intestinal inflammation and damage suffered by human patients. Drs. Wang and Au and their colleagues injected the animals with a mixture of colon cells and the extracellular matrix that typically surrounds them – simulating the tissue typically attacked in ulcerative colitis – along with polymer nanofibers chemically altered to carry a variety of proteins and other molecules that cancer cells use to suppress immune activity.

Kin Man Au, Ph.D., Assistant Professor of Radiation Oncology, is the study's first author.

These injections not only significantly reduced symptoms of ulcerative colitis, such as diarrhea, rectal bleeding, weight loss, and inflammation-associated colon shortening, but tissue analysis showed that this treatment also reduced immune cell infiltration into the colon’s lining and its concentration of inflammatory molecules. Within seven days after injection, researchers saw that the colon’s lining appeared completely healed in mice that received the combination. Those treated with only parts of the combination or no injection at all still had actively inflamed colon lesions, the study showed.

The treatment also reduced the number of cancerous colon tumors that were developed by 60% (both animal models and human patients with ulcerative colitis have an increased risk of colon cancer). Additionally, the injections appeared to target only immune activity against the colon and did not suppress immunity broadly in the body. When the researchers gave injections to mouse models of ulcerative colitis that also carried melanoma and colon tumors, these animals responded to immunotherapy for their cancer, which would not be possible if they were systemically immunosuppressed.

Together, Dr. Wang said, these findings suggest that the combination injections could be a viable new way of treating ulcerative colitis. A similar approach may also be used to treat other autoimmune diseases. He and his colleagues have filed a patent to develop this strategy into a clinical treatment.

Dr. Wang holds the A. Kenneth Pye Professorship in Cancer 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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

The findings, published in the World Journal of Surgical Oncology, show that patients undergoing robotic surgery in the vast majority of colectomies – the surgical removal of a portion of the large intestine – experienced shorter hospital stays and lower rates of complications. Additionally, they had more lymph nodes harvested and, as a result, had a more accurate determination of what stage the cancer was in.

They also had fewer conversions to open surgery necessitated by anatomical challenges and fewer instances of postoperative ileus – the inability of the intestine to contract naturally, which can lead to a life-threatening blockage.

Patricio M. Polanco, M.D., is Associate Professor of Surgery in the Division of Surgical Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center. His work is supported by the Eugene P. Frenkel, M.D. Scholar Award from Simmons Cancer Center.

“Colorectal cancer is one of the most common types of cancer with more than 150,000 new cases in the U.S. every year,” said study leader Patricio M. Polanco, M.D., Associate Professor of Surgery in the Division of Surgical Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center. He is also Director of UTSW’s Robotic Surgery Training Program and co-Director of the Pancreatic Cancer Program. 

“Robotic surgery for colectomies is quickly becoming the preferred approach due to its multiple benefits for the surgeon, which include better 3D visualization and a stable camera, improved dexterity and instrument control, and reduced fatigue and hand tremor,” he said. “Prior to this study, however, there was little real-world evidence demonstrating its efficacy compared to laparoscopic techniques.”

While both laparoscopic and robotic surgery are considered minimally invasive and use small incisions and a camera to view the procedure, there are important differences. Surgeons performing laparoscopy manipulate the tools by hand and use a thin, telescopic rod outfitted with a tiny 2D camera – called a laparoscope – to view the surgical site.

Robotic surgery has a control console that the surgeon uses to maneuver the robotic arms outfitted with surgical tools. This more advanced technology not only creates a higher-quality 3D view of the procedure, but it also offers better precision and range of motion and eliminates any hand tremors from the surgeon.

To compare the outcomes achieved by the two forms of surgery, UTSW researchers conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2015-2020. A total of 53,209 colectomy cases from across the U.S. were included.

Colorectal procedures were identified by location – right and left colectomies, which comprise the majority of colorectal cancer surgeries, and low anterior resections, which involve the rectum. Textbook outcome was defined as the absence of 30-day complications, readmission, and mortality, and a postoperative length of stay of fewer than five days. 

The study found that 71% of the robotic procedures for right colectomies resulted in textbook outcomes compared with 64% for laparoscopic treatments. The results were similar for left colectomies at 75% versus 68%. 

Only low anterior resection procedures fared better with laparoscopy, with the study showing that the use of robotic surgery was associated with higher rates of postoperative ileus (11.9% versus 10.5%), hospital readmission (10.4% versus 9.1%), and major morbidity (7.1% versus 5.8%), with comparable rates of textbook outcomes (68% versus 67%). While the exact reason for the discrepancy can’t be determined with current data, Dr. Polanco said he believes that these small differences favoring the laparoscopic approach correspond to the higher complexity of rectal resections and surgeons’ longer experience with the procedure.

“The growth in robotic surgery and the alarming increase in colorectal cancer in younger adults are two of the most significant trends we have seen in recent years, both of which highlight the importance of optimizing surgical treatment strategies,” Dr. Polanco said. “These findings are critical because they give us a deeper understanding of the benefits and drawbacks of robotic surgery and can help patients and their surgical teams make informed decisions regarding their treatment.” 

The study builds on earlier research at UTSW on the benefits of robotic surgery in the treatment of pancreas and liver cancer. Dr. Polanco’s work is supported by the Eugene P. Frenkel, M.D. Scholar Award from Simmons Cancer Center.

Other UTSW researchers from Surgery who contributed to this study are Herbert J. Zeh III, M.D., Chair and Professor of Surgery; Javier Salgado, M.D., Associate Professor and Section Chief of Colorectal Surgery; Emile Farah, M.D., Postdoctoral Research Fellow; Andres A. Abreu, M.D., Postdoctoral Research Fellow; and Benjamin Rail, B.S. Dr. Zeh holds the Hall and Mary Lucile Shannon Distinguished University Chair in Surgery.

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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Dec. 15, 2023 – The U.S. Food & Drug Administration has expanded the approved use of belzutifan for treatment of metastatic kidney cancer, another milestone for the novel, first-in-class kidney cancer drug arising from scientific discoveries at UT Southwestern Medical Center.

Following the discovery of the hypoxia-inducible factor 2-alpha (HIF-2α) gene at UT Southwestern, its scientists solved the HIF-2α protein structure, pinpointing a potential vulnerability. The UTSW team then conducted a comprehensive drug screen to identify possible therapeutic compounds and established Peloton Therapeutics, which developed the drug. Peloton was ultimately acquired by the pharmaceutical giant Merck, which markets belzutifan under the brand name Welireg.

Texas businessman Mark Hilz was first diagnosed with kidney cancer in 2011 and started taking belzutifan earlier this year. (Photo credit: Courtesy Mark Hilz)

Belzutifan was initially approved by the FDA in 2021 for familial kidney cancer. The latest approval follows completion of the Litespark-005 phase three clinical trial and broadens the drug’s label to anyone with advanced renal cell carcinoma.

“This remarkable journey exemplifies UT Southwestern’s dedication to converting important scientific discoveries into improvements in patient care and underscores the power of innovation and team science in advancing health care,” said 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. “With the FDA’s approval, thousands of patients in need will gain access to this important new treatment.”

Mark Hilz, a 65-year-old Texas businessman who enjoys spending time with his eight grandchildren, was first diagnosed with kidney cancer in 2011. By May 2023, he was running out of options that would preserve his outstanding quality of life. Dr. Brugarolas recommended belzutifan, and it made a difference, reducing the size of some tumors and stopping the growth of others.

“It was starting to look like I had an expiration date,” said Mr. Hilz, who takes three pills daily to keep his cancer under control. “Imagine being stage 4 and then getting a restart. I’m also able to maintain a great quality of life on this treatment.”

A journey of innovation

HIF-2α was discovered in the 1990s by Steven McKnight, Ph.D., Professor of Biochemistry, and David Russell, Ph.D., Professor Emeritus of Molecular Genetics, at UT Southwestern. The gene was subsequently found to play a key role in the growth of kidney cancer. UTSW scientists Kevin Gardner, Ph.D., and Richard Bruick, Ph.D., then studied the protein structure, identifying an unusual cavity within HIF-2α and demonstrating that chemical compounds could bind to that vulnerable area.

Led by Drs. Bruick and Gardner, the next phase involved a rigorous drug screen of UT Southwestern’s chemical library to identify specific compounds that could block HIF-2α function. Building on their momentum, UT Southwestern incubated Peloton Therapeutics within its BioCenter and transformed the scientific innovation into a tangible therapy.

Dr. Brugarolas tested mice transplanted with human kidney cancers and determined that the drug was effective against the tumors. Kevin Courtney, M.D., Ph.D., Associate Professor of Internal Medicine and Chair of the Protocol Review & Monitoring Committee of the Simmons Cancer Center, conducted the first clinical trial of a HIF-2α inhibitor and found the drug to be well-tolerated and effective among patients with kidney cancer. More than half of the participants saw their cancer regress or stabilize with the drug. Drs. Brugarolas and Courtney then established that HIF-2α is a core dependency for many kidney tumors.

Merck recognized the drug’s transformative potential and acquired Peloton in 2019.

In 2021, the FDA approved belzutifan for adult patients with von Hippel-Lindau (VHL) disease, a familial kidney cancer condition. VHL patients develop renal cell carcinoma, central nervous system hemangioblastomas, and pancreatic neuroendocrine tumors, and all of those types respond to the therapy.

In 2023, results were reported from a phase three trial evaluating belzutifan for treatment of clear cell renal cell carcinoma that progressed on prior immune and targeted therapies. The study showed a statistically significant and clinically meaningful delay in tumor progression compared with everolimus, the former standard of care. These results led to an expanded FDA approval on Dec. 14 to treat the most common type of kidney cancer.

Cancer care at UTSW

The Kidney Cancer Program within UTSW’s Simmons Cancer Center is one of only two National Cancer Institute-designated Specialized Programs of Research Excellence (SPOREs) in kidney cancer. Established in 2013, the program has become a leader worldwide in kidney cancer.

The Simmons Cancer Center is one of 33 members of the National Comprehensive Cancer Network and one of 56 National Cancer Institute-Designated Comprehensive Cancer Centers. The Simmons Cancer Center is ranked 19th for cancer care among over 800 cancer hospitals by U.S. News & World Report. Its faculty members treat more than 9,000 new cancer patients a year, participate in over 300 active clinical trials, and have more than $100 million in extramural cancer-focused research funding.

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

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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Dec. 14, 2023 – Despite the convenience of at-home screening tests for early detection of colorectal cancer (CRC), a study led by UT Southwestern Medical Center researchers examining more than a decade of patient data found that about 10% of the tests could not be processed, mostly due to patient error.

Rasmi Nair, M.B.B.S., M.P.H., Ph.D., is Assistant Professor in the Peter O'Donnell Jr. School of Public Health at UT Southwestern.

The findings, published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, provide critical insights into challenges that patients have collecting a specimen, properly labeling samples, and completing follow-up tests in a timely manner.

“The study underscores the importance of addressing breakdowns in the screening process, particularly in specimen collection and labeling,” said corresponding author Rasmi Nair, M.B.B.S., M.P.H., Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health at UT Southwestern. “Understanding and mitigating barriers to successful colorectal cancer screening is critical for improving CRC outcomes.”

Dr. Nair co-led the research with Po-Hong Stuart Liu, M.D., M.P.H., Clinical Research Fellow in the Division of Digestive and Liver Diseases at UT Southwestern.

The at-home tests for CRC are often more convenient, less costly, and less invasive than a colonoscopy or other stool-based tests.

This retrospective study looked at in-home fecal immunochemical tests (FIT) submitted between 2010 and 2019 from 56,980 individuals who had a primary care visit through Parkland Health in the year prior to the test. Parkland Health is a safety net hospital system in Dallas County and UT Southwestern’s primary teaching hospital. Patients of average CRC risk between ages 50 and 74 were included in the analysis to determine the rates of unsatisfactory FITs and subsequent follow-up testing.

Dr. Nair and her team discovered that more than 10% of FIT samples could not be processed in the laboratory; that rate is double the 5% recommended threshold set by the U.S. Multi-Society Task Force on Colorectal Cancer. Inadequate specimen collection (51%), incomplete labeling (27%), age of specimen (13%), and broken or leaking containers (8%) were the primary causes of failed tests. The study also found higher failure rates among patients who were male, Black, or Spanish-speaking, or on Medicaid. Additionally, patients who received kits in the mail rather than from a practitioner were at greater risk of test failure.

Researchers advocate for more robust patient education strategies, better test-tracking procedures, and timely follow-up of problem tests to reduce FIT failure rates and improve patient care through early CRC interventions. Researchers also anticipate that their findings will boost the effectiveness of other at-home testing services. 

“Our findings could impact other at-home tests such as fecal DNA tests for CRC screening and future home testing for human papillomavirus, for instance,” Dr. Nair said. “Understanding the reasons for unsatisfactory home tests, implementing automatic ordering of subsequent tests, and ensuring appropriate completion of tests and follow-up become increasingly important.” 

Other UTSW researchers who contributed to this study were Celette Sugg Skinner, Ph.D., Professor in the O’Donnell School of Public Health and a member of the Harold C. Simmons Comprehensive Cancer Center; Noel Santini, M.D., M.B.A., Clinical Associate Professor of Internal Medicine at UT Southwestern and Vice President and Senior Medical Director of Ambulatory & Population Medicine at Parkland Health; and Cynthia Ortiz, M.P.H., Ellen Hu, M.H.S., and Jacquelyn M. Lykken, Ph.D., all with the O’Donnell School of Public Health.

This study was funded by grants from the National Institutes of Health (U54 CA163308, UM1 CA222035, and T32 DK007745) and the Cancer Prevention and Research Institute of Texas (PP160075).

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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

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.

Jinming Gao, Ph.D., Professor of Biomedical Engineering, Cell Biology, Otolaryngology - Head and Neck Surgery, and Pharmacology at UT Southwestern, holds the Elaine Dewey Sammons Distinguished Chair in Cancer Research, in Honor of Eugene P. Frenkel, M.D.

Since its inception in 2012, the NAI Fellows program has grown to include 1,898 researchers and innovators who hold over 63,000 U.S. patents and 13,000 licensed technologies. This year’s class includes 162 inventors from 118 research universities and governmental and nonprofit research institutions worldwide.

“It is an honor to join this talented and accomplished group of international innovators striving to develop new technologies to benefit society,” said Dr. Gao, who is also a Professor in the Harold C. Simmons Comprehensive Cancer Center. Dr. Gao holds 16 U.S. patents and 72 foreign patents in the fields of polymer biomaterials, nanoparticle drug delivery, tumor surgical imaging, and cancer immunotherapy. Thirteen of the patents have been licensed to biotech companies.

Dr. Gao’s studies focus on the intersection of nanotechnology and cancer medicine. He and his colleagues in the Gao Lab have developed synthetic polymer nanoparticles that release their payload after entering an acidic environment, like that surrounding cancer cells. The first adaptation of the technology, pegsitacianine, carries fluorescent dyes that illuminate the boundaries of solid tumors for real-time surgical imaging.

This technology was licensed by OncoNano Medicine Inc., a startup co-founded by Dr. Gao and Baran Sumer, M.D., Professor of Otolaryngology – Head and Neck Surgery at UTSW. It recently completed a phase two clinical trial in cytoreductive surgery of peritoneal metastasis and has received a breakthrough therapy designation from the U.S. Food and Drug Administration, a status designed to expedite development and regulatory review of medicines.

Dr. Gao and his colleagues also created PC7A nanoparticles, a “nanovaccine” that has shown promise in preclinical studies. These nanoparticles carry tumor antigens to immune cells, leading to the production of tumor-specific T cells that kill cancer cells. Dr. Gao’s team has also developed nanoparticles that inhibit a protein that cancer cells use to pump out acid to suppress cytotoxic T cells, resulting in improved antitumor immunity and survival in animal models.

“Dr. Gao’s contributions to nanotechnologies focused on cancer hold enormous potential to fight this disease in completely new ways,” said Samuel Achilefu, Ph.D., Chair and Professor of Biomedical Engineering at UT Southwestern who is also an NAI Fellow.

Dr. Gao joined UT Southwestern in 2005 from Case Western Reserve University, where he served on the faculty for seven years. Before that appointment, he received his Ph.D. from Harvard University in 1996 and completed a postdoctoral fellowship at Massachusetts Institute of Technology.

Dr. Gao joins four other NAI members at UT Southwestern: Dr. Achilefu; Michael Brown, M.D., Professor of Molecular Genetics, and Joseph Goldstein, M.D., Chair and Professor of Molecular Genetics, winners of the 1985 Nobel Prize in Physiology or Medicine; and Martin Pomper, M.D., Ph.D., Chair and Professor of Radiology. Abd El Kareem Azab, Ph.D., Associate Professor of Biomedical Engineering, is a Senior Member. 

Drs. Achilefu, Pomper, and Sumer are all members of the Simmons Cancer Center.

Dr. Achilefu holds the Lyda Hill Distinguished University Chair in Biomedical Engineering. 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. Gao holds the Elaine Dewey Sammons Distinguished Chair in Cancer Research, in Honor of Eugene P. Frenkel, M.D. 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. Dr. Pomper holds the Effie and Wofford Cain Distinguished Chair in Diagnostic Imaging. Dr. Sumer holds the T.C. Lupton Family Professorship in Patient Care, in Honor of Dr. John Dowling McConnell and Dr. David Andrew Pistenmaa.

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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Dec. 11, 2023 – Researchers at UT Southwestern Medical Center have developed a novel artificial intelligence (AI) model that analyzes the spatial arrangement of cells in tissue samples. This innovative approach, detailed in Nature Communications, accurately predicted outcomes for cancer patients, marking a significant advancement in utilizing AI for cancer prognosis and personalized treatment strategies.

Guanghua Xiao, Ph.D., Professor in the Peter O’Donnell Jr. School of Public Health, Biomedical Engineering, and the Lyda Hill Department of Bioinformatics at UT Southwestern, holds the Mary Dees McDermott Hicks Chair in Medical Science.

“Cell spatial organization is like a complex jigsaw puzzle where each cell serves as a unique piece, fitting together meticulously to form a cohesive tissue or organ structure. This research showcases the remarkable ability of AI to grasp these intricate spatial relationships among cells within tissues, extracting subtle information previously beyond human comprehension while predicting patient outcomes,” said study leader Guanghua Xiao, Ph.D., Professor in the Peter O’Donnell Jr. School of Public Health, Biomedical Engineering, and the Lyda Hill Department of Bioinformatics at UT Southwestern. Dr. Xiao is a member of the Harold C. Simmons Comprehensive Cancer Center at UTSW.

Tissue samples are routinely collected from patients and placed on slides for interpretation by pathologists, who analyze them to make diagnoses. However, Dr. Xiao explained, this process is time-consuming, and interpretations can vary among pathologists. In addition, the human brain can miss subtle features present in pathology images that might provide important clues to a patient’s condition.

Various AI models built in the past several years can perform some aspects of a pathologist’s job, Dr. Xiao added – for example, identifying cell types or using cell proximity as a proxy for interactions between cells. However, these models don’t successfully recapitulate more complex aspects of how pathologists interpret tissue images, such as discerning patterns in cell spatial organization and excluding extraneous “noise” in images that can muddle interpretations.

The new AI model, which Dr. Xiao and his colleagues named Ceograph, mimics how pathologists read tissue slides, starting with detecting cells in images and their positions. From there, it identifies cell types as well as their morphology and spatial distribution, creating a map in which the arrangement, distribution, and interactions of cells can be analyzed.

The researchers successfully applied this tool to three clinical scenarios using pathology slides. In one, they used Ceograph to distinguish between two subtypes of lung cancer, adenocarcinoma or squamous cell carcinoma. In another, they predicted the likelihood of potentially malignant oral disorders – precancerous lesions of the mouth – progressing to cancer. In the third, they identified which lung cancer patients were most likely to respond to a class of medications called epidermal growth factor receptor inhibitors.

In each scenario, the Ceograph model significantly outperformed traditional methods in predicting patient outcomes. Importantly, the cell spatial organization features identified by Ceograph are interpretable and lead to biological insights into how individual cell-cell spatial interaction change could produce diverse functional consequences, Dr. Xiao said.

These findings highlight a growing role for AI in medical care, he added, offering a way to improve the efficiency and accuracy of pathology analyses. “This method has the potential to streamline targeted preventive measures for high-risk populations and optimize treatment selection for individual patients,” said Dr. Xiao, a member of the Quantitative Biomedical Research Center at UT Southwestern.

Shidan Wang, Ph.D., a former faculty member in the O’Donnell School of Public Health, was the study’s first author. Other UTSW researchers who contributed to the research are Yang Xie, Ph.D., Professor in the O’Donnell School of Public Health and the Lyda Hill Department of Bioinformatics; John Minna, M.D., Professor of Internal Medicine and Pharmacology and Director of the Hamon Center for Therapeutic Oncology Research; Justin Bishop, M.D., Professor of Pathology; Xiaowei Zhan, Ph.D., Associate Professor in the O’Donnell School of Public Health and the Center for the Genetics of Host Defense; Siyuan Zhang, M.D., Ph.D., Associate Professor of Pathology; Ruichen Rong, Ph.D., and Donghan M. Yang, Ph.D., Assistant Professors in the O’Donnell School of Public Health; Zhikai Chi, M.D., Ph.D., Assistant Professor of Pathology; Qin Zhou, Ph.D., Postdoctoral Researcher; and Xinyi Zhang, Ph.D., Graduate Student Researcher.

Dr. Xiao holds the Mary Dees McDermott Hicks Chair in Medical Science.

This study was funded by grants from the National Institutes of Health (P50CA070907, R01GM140012, R01DE030656, R01GM115473, 1U01CA249245, R35GM136375, P30CA008748, and P30CA142543) and the Cancer Prevention and Research Institute of Texas (CPRIT RP180805 and CPRIT RP230330).

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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Dec. 05, 2023 – A new study led by UT Southwestern Medical Center molecular biologists presents a novel culture system to grow both embryonic and extraembryonic stem cells, potentially providing important insights into the genesis of congenital malformations and early developmental disorders.

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

Published in Cell, the report by an international team of researchers from the U.S., China, and Japan outlines procedures for establishing a culture system that, for the first time, permits the simultaneous derivation and co-culture of stem cells from both embryonic and extraembryonic tissues.

“These findings represent significant progress in stem cell and developmental biology through the development of a unified stem cell culture system. The use of this novel system not only deepens our understanding of the interplay between embryonic and extraembryonic cells during embryogenesis but also sets the stage for the creation of more precise models of embryonic development and improved stem cell differentiation protocols,” said lead author Jun Wu, Ph.D., Associate Professor of Molecular Biology and a Virginia Murchison Linthicum Scholar in Medical Research at UT Southwestern.

In addition to outlining the new unified growth conditions for embryonic and extraembryonic stem cells, the study:

• Reveals critical interactions between different embryonic and extraembryonic cell types, such as the growth inhibition of pluripotent cells by extraembryonic endoderm cells, and emphasizes the importance of cell-to-cell communication during embryogenesis.
• Identifies both common and unique factors involved in regulating extraembryonic endoderm stem cells across different species.

“This fundamental research in stem cell biology holds the potential to provide crucial insights into the genesis of congenital malformations and early developmental disorders. The insights derived from this study lay the groundwork for potentially preventive and therapeutic strategies for such conditions,” noted Dr. Wu, a member of the Hamon Center for Regenerative Science and Medicine and the Cecil H. and Ida Green Center for Reproductive Biology Sciences at UT Southwestern. He was recruited in 2017 through the First-Time, Tenure-Track Faculty Member program from the Cancer Prevention and Research Institute of Texas (CPRIT).

“Overall, the ability to mimic natural embryonic environments in vitro can significantly advance the study of early human development and diseases, potentially leading to novel treatments and prevention strategies,” said first author Yulei Wei, Professor in the College of Biological Sciences at the China Agricultural University in Beijing, who completed her postdoctoral training in 2022 in the Wu Lab at UT Southwestern.

The new findings build upon the Wu Laboratory’s earlier work, which has contributed to the generation of novel stem cells for basic and translational studies. Researchers have identified several new types of pluripotent stem cells (PSCs) with distinct molecular and phenotypic features from different species and generated PSC-derived interspecies chimeras and a blastocyst complementation system for the generation of organs and tissues. Most recently, Dr. Wu’s group has developed strategies to generate stem cell embryo models for studying peri-implantation development in vitro.

In a 2021 study published in Cell Stem Cell, the Wu Lab devised a culture method that could generate an intermediate, also referred to as formative, state of pluripotent stem cells from the blastocysts of mice and horses. The current investigation discovered that the same culture condition can be used to derive both embryonic stem cells and extraembryonic stem cells, such as trophoblast stem cells and extraembryonic endoderm stem cells, from the blastocysts of mice and primates.

The new study furthers the Wu Lab’s research into interactions between embryonic and extraembryonic tissues in early mammalian development utilizing stem cell-based embryo models. Previous work has successfully developed stem cell models of early mammalian embryos, including mouse, bovine, and human blastocyst-like structures (termed blastoids), as well as structures resembling the human peri-gastrulation stage (referred to as human peri-gastruloids).

The findings have the potential to impact research and therapeutic approaches for a variety of diseases and conditions, particularly those related to:

• Developmental disorders: Understanding the coordination between embryonic and extraembryonic tissues can shed light on congenital malformations and developmental disorders that occur during early embryogenesis.
• Placental abnormalities: Insights into trophoblast stem cells that contribute to placenta formation may improve the understanding of placental dysfunctions, such as preeclampsia or placenta accreta.
• Regenerative medicine: The ability to co-culture embryonic and extraembryonic stem cells may enhance tissue engineering and the development of organoids. This could benefit conditions requiring tissue regeneration.
• Cancer research: Since some cancers involve signaling pathways common to stem cell regulation, such as FGF, TGF-β, and WNT, this research may contribute to understanding tumor growth and metastasis.
• Reproductive health: The study may lead to advancements in fertility treatments by improving the understanding of early embryonic development and the implantation processes.

Dr. Wu is a member of the Harold C. Simmons Comprehensive Cancer Center at UTSW and a 2021 Robertson Stem Cell Investigator through The New York Stem Cell Foundation.

Other UTSW researchers who contributed to this study are Wu Lab members Masahiro Sakurai, Ph.D., Assistant Instructor; Lizhong Liu, Ph.D., Assistant Instructor; Daniel A. Schmitz, Graduate Student; and Yi Ding, Ph.D., Postdoctoral Research Fellow. Additional contributing UTSW researchers are Lin Xu, Ph.D., Assistant Professor, and Lei Guo, Ph.D., Computational Biologist, both in the Quantitative Biomedical Research Center in the Peter O’Donnell Jr. School of Public Health. Dr. Xu is also a member of the Simmons Cancer Center.   

The work in the Wu Lab is supported by The New York Stem Cell Foundation, National Institutes of Health grants (GM138565-01A1 and HD103627-01A1), a Discovery and Innovation Grant from the American Society for Reproductive Medicine (ASRM) Research Institute, and The Welch Foundation (I-2088).

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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Dec. 04, 2023 – UT Southwestern Medical Center’s Harold C. Simmons Comprehensive Cancer Center is among the first in the nation and the first in Texas to offer radiation treatments using a new technology that combines positron emission tomography (PET) imaging with radiotherapy to precisely treat bone and lung cancers.

Aurelie Garant, M.D., Assistant Professor of Radiation Oncology, leads the Brachytherapy Program at UT Southwestern.

SCINTIX biology-guided radiotherapy (BgRT), delivered by the RefleXion X1 unit, is an option for patients with primary and metastatic bone and lung cancers. Using a radioactive tracer that interacts with cancer cells to produce photonic signals from emissions, the system makes tumors their own worst enemy by using cancer’s acquired activity to specifically target diseased tissue.

“In essence, we are now able to assess the exact location of one or multiple tumors, as well as their individual biological signatures,” said Aurelie Garant, M.D., Assistant Professor of Radiation Oncology and member of the Simmons Cancer Center who leads the Brachytherapy Program. “Given that not all tumors are created equal, biology-guided radiotherapy provides us with the unique opportunity to target the areas that are most biologically active, while sparing normal tissues.”

Robert Timmerman, M.D., Chair and Professor of Radiation Oncology and Professor of Neurological Surgery, holds the Effie Marie Cain Distinguished Chair in Cancer Therapy Research.

Approximately 430,000 people in the United States are diagnosed annually with tumors originating within or spreading to the lungs or bones. Until now, treating multiple targets has been challenging due to workflows in the way traditional radiation therapy is delivered, but SCINTIX may provide an effective way to treat multiple targets seen in PET scans.

SCINTIX’s novel technology uses each cancer’s biologic processes to determine how much radiation to deliver, even if the target moves. The X1 continuously constructs a map from emissions data to target the locations for beamlets of radiation, delivered with subsecond speed. At the same time, SCINTIX tracks tumor motion generated by internal processes such as breathing and digestion as well as movement by patients. This accurate tracking may reduce the amount of radiation to healthy cells that surround cancerous tissue.

Arnold Pompos, Ph.D., Associate Professor of Radiation Oncology, is Associate Vice Chair of Strategic Initiatives and Capital Investments at UT Southwestern.

"Owing to the tumor’s continuous emission of a distinct signal at fractional-second intervals, SCINTIX possesses the advanced capability to detect these unique emissions. This innovation enables us to provide our patients with a revolutionary radiation treatment technology,” said Arnold Pompos, Ph.D., Associate Professor of Radiation Oncology and Associate Vice Chair of Strategic Initiatives and Capital Investments. “It is designed to precisely target and administer therapeutic radiation to the tumor, adapting in real time to its movement. This approach represents the fulfillment of a critical objective in oncological care: the ability to accurately track and effectively treat moving tumors."

“Biology-guided radiotherapy is an excellent demonstration of multiple technologies merging into one treatment modality,” said Robert Timmerman, M.D., Chair and Professor of Radiation Oncology and member of the Simmons Cancer Center and the Peter O’Donnell Jr. Brain Institute. “This technology will likely broaden the scope of scenarios where radiotherapy may play a critical role.”

Orhan Oz, M.D., Ph.D., Professor of Radiology and Chief of Nuclear Medicine at UT Southwestern, holds the Robert W. Parkey, M.D. Distinguished Professorship in Radiology and The Wechun Pak Professorship of Bone Biophysics.

Orhan Oz, M.D., Ph.D., Professor of Radiology, Chief of Nuclear Medicine at UTSW, a member of the Simmons Cancer Center, and a co-investigator in the clinical trial that led to U.S. Food and Drug Administration approval, added: “We hope life-prolonging treatments with limited levels of toxic side effects will be discovered using this platform.”

The technology received Breakthrough Device designation in 2021 from the FDA and clearance to use the therapy for lung and bone cancer treatment in 2023. UT Southwestern, which led a study on its efficacy, was only the second institution in the country to install it.

Bin Cai, Ph.D., Associate Professor of Radiation Oncology, is Director of Advanced Physics Service at UT Southwestern.

"I believe one of the next revolutionary changes in our field lies in biology-guided radiation therapy and functional adaptation,” said Bin Cai, Ph.D., Associate Professor of Radiation Oncology and Director of Advanced Physics Service, who led the deployment of SCINTIX BgRT at UT Southwestern from the technology side. “Therefore, we are committed to introducing this groundbreaking treatment strategy to the field safely, delivering high-quality solutions to our patients, effecting meaningful clinical changes for their benefit, and collectively offering a novel and powerful strategy to combat cancer.”

SCINTIX is the latest technology available at UT Southwestern’s Radiation Oncology facility. With more than a dozen advanced imaging/treatment machines in 130,000 square feet of space, UTSW offers patients a personalized experience to treat an array of cancers through artificial intelligence-assisted radiation therapy that adapts to changes in the patient’s anatomy, tumor size, and position.

The UTSW Simmons Cancer Center is one of 56 centers nationwide designated as a Comprehensive Cancer Center by the National Cancer Institute and the only one in North Texas. It is also a member of the elite National Comprehensive Cancer Network (NCCN), and ranked 19^th for cancer care among over 800 cancer hospitals by U.S. News & World Report.

Dr. Oz, a member of the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research at UTSW, is also Medical Director of Nuclear Medicine at Parkland Health. He holds the Robert W. Parkey, M.D. Distinguished Professorship in Radiology and The Wechun Pak Professorship of Bone Biophysics.

Funding for the study conducted by Drs. Timmerman, Garant, Pompos, Cai, and other UTSW colleagues was provided by RefleXion Medical. Dr. Timmerman, who is also a Professor of Neurological Surgery and holds the Effie Marie Cain Distinguished Chair in Cancer Therapy Research, serves on the scientific advisory board of RefleXion. Drs. Pompos and Cai have received speaking engagement fees from RefleXion.

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 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Nov. 28, 2023 – Colorectal cancer (CRC) screening rates are similar among older adults despite varying 10-year mortality risks, UT Southwestern Medical Center researchers report in a new study. The findings, published in The American Journal of Gastroenterology, challenge conventional age-based recommendations for CRC screening that don’t take into account factors like individual life expectancies and comorbidities.

Amit Singal, M.D., M.S., Professor of Internal Medicine in the Division of Digestive and Liver Diseases, is a member of the Peter O'Donnell Jr. School of Public Health and the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Singal is also Medical Director of the UTSW Liver Tumor Program, Chief of Hepatology, and a Dedman Family Scholar in Clinical Care.

“We were surprised to see little difference in colorectal cancer screening rates across life expectancy groups despite patients having differences in the anticipated risk-benefit ratio of the procedure,” said co-senior author Amit Singal, M.D., M.S., Professor of Internal Medicine in the Division of Digestive and Liver Diseases and member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Singal is also Medical Director of the UTSW Liver Tumor Program, Chief of Hepatology, and a Dedman Family Scholar in Clinical Care. 

The research revealed the potentially significant benefits of updating the current CRC guidelines, which call for screenings based primarily on age starting at 45 and stopping at 75. A more personalized approach, which considers a person’s health status and risk of dying in the next 10 years, would ensure that both older, healthier adults and younger individuals with chronic conditions receive the appropriate level of screening.

“Our results suggest incorporating life expectancies and comorbidities into current age-based recommendations for colorectal cancer screening,” said Po-Hong Stuart Liu, M.D., M.P.H., Clinical Research Fellow in the Division of Digestive and Liver Diseases at UT Southwestern and the study’s first author. “The traditional one-size-fits-all approach doesn’t account for the varying health statuses and life expectancies of older adults, potentially leading to underscreening and overscreening.”

Po-Hong Stuart Liu, M.D., M.P.H., Clinical Research Fellow in the Division of Digestive and Liver Diseases at UT Southwestern, is the study's first author.

The study analyzed the behaviors of 25,888 adults, ages 65-84, who were not up to date with CRC screening based on National Health Interview Survey data. The researchers specifically focused on screening for colorectal cancer within the past year, which included any recommended CRC screening test. They found that the prevalence of these screenings remained consistent, ranging from 35.4% to 40.6% across various 10-year mortality risk categories, offering compelling evidence for revising the existing age-based framework.

With the growing incidence of CRC diagnoses after age 65 and the number of those adults projected to increase from 55.8 million in 2020 to 81 million in 2040, the findings drive home the importance of identifying older patients who may benefit from screening while simultaneously identifying those younger than 75 who may not benefit from the same screening measures.

“Beyond implications for CRC screening guidelines, our data reinforce the importance of providers considering whether patients can truly derive long-term benefits from screening,” Dr. Singal noted. “Specifically, screening is unlikely to be of benefit in patients with a high competing risk of mortality from other medical conditions.”

The study was funded by grants from the National Institutes of Health (R01CA242558 and T32DK007745).

Dr. Singal is a member of the Peter O’Donnell Jr. School of Public Health and holds the Willis C. Maddrey, M.D. Distinguished Chair in Liver Disease.

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 26 members of the National Academy of Sciences, 20 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Nov. 22, 2023 – More than a dozen UT Southwestern Medical Center scientists are included on the 2023 Highly Cited Researchers list, which recognizes the top 1% of researchers from around the world who have demonstrated significant and broad influence in their chosen field or fields of research.

Considered a who’s who of influential researchers, the Highly Cited Researchers list is produced each year by the Institute for Scientific Information at Clarivate, a British analytics company. It highlights scientists who have published multiple highly cited papers over the last decade and rank in the top 1% of citations for a field or fields. This year’s list includes 6,849 researchers from institutions in 67 countries who represent 0.1% of the world's population of scientists and social scientists.

At UT Southwestern, this year’s Highly Cited Researchers work in Biochemistry, Biophysics, Cancer Biology, Cardiology, Cell Biology, Genetics, Immunology, Molecular Biology, Pediatrics, Pharmacology, and Surgery. The list includes leaders from UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, Hamon Center for Regenerative Science and Medicine, Hamon Center for Therapeutic Oncology Research, Peter O’Donnell Jr. Brain Institute, Touchstone Diabetes Center, Harry S. Moss Heart Center, Center for Depression Research and Clinical Care, Children’s Medical Center Research Institute at UT Southwestern, Center for Inflammation Research, and the Peter O’Donnell Jr. School of Public Health. 

“The Highly Cited Researchers list identifies and celebrates exceptional individual researchers at UT Southwestern Medical Center whose significant and broad influence in their fields translates to impact in their research community and innovations that make the world healthier, more sustainable, and more secure,” said David Pendlebury, Head of Research Analysis at the Institute for Scientific Information at Clarivate. “Their contributions resonate far beyond their individual achievements, strengthening the foundation of excellence and innovation in research.” 

The Highly Cited Researchers listing comes atop other recent recognition for research at UT Southwestern. 

UT Southwestern is ranked as the top-rated public institution and No. 3 among health care institutions globally by Nature Index for publishing high-quality research. Its scientists are currently leading about 5,800 research projects with more than $643 million in support from the National Institutes of Health, the state of Texas, foundations, individuals, and corporations. UT Southwestern is also ranked fourth in the nation and No. 1 in Texas by Heartland Forward for commercializing new biomedical technologies. 

In addition, UT Southwestern’s William P. Clements Jr. University Hospital is on U.S. News & World Report’s national Honor Roll of top hospitals, ranked No. 1 in Texas (tied) and, for the seventh year in a row, No. 1 in Dallas-Fort Worth – the nation’s fourth-largest metro area.  

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 26 members of the National Academy of Sciences, 20 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year. 

Carlos L. Arteaga, M.D., is Director of the Harold C. Simmons Comprehensive Cancer Center and Associate Dean of Oncology Programs at UT Southwestern Medical Center.

“This novel combination therapy showed very encouraging results, even in patients who failed several other lines of treatment,” said co-lead author Carlos L. Arteaga, M.D., Director of the Harold C. Simmons Comprehensive Cancer Center and Associate Dean of Oncology Programs at UT Southwestern.

Based on the results of this study, the National Comprehensive Cancer Network has added this three-drug combination to its treatment guidelines.

Research has found that close to 10% of patients with metastatic breast cancer harbor cancer-promoting HER2 mutations. Although these tumors initially respond to HER2-inhibiting drugs, studies have shown that they eventually stop responding after new mutations develop.

Seeking a way to slow or stop progression of tumors bearing HER2 mutations, Dr. Arteaga and his colleagues – including Nisha Unni, M.D., Associate Professor of Internal Medicine, and Ariella Hanker, Ph.D., Assistant Professor of Internal Medicine, both members of the Simmons Cancer Center – tested various combinations of three different drugs among 71 breast cancer patients being treated at 23 medical centers around the world. All of the patients were positive for mutations in their HER2 gene as well as hormone receptors, cell-surface proteins that can fuel cell growth and often occur in conjunction with HER2 overactivity. These patients had failed an average of three systemic cancer treatments.

Fifty-seven patients received a combination of neratinib, a HER2 tyrosine kinase inhibitor; fulvestrant, which inhibits estrogen receptors; and trastuzumab, a HER2 blocking antibody. Seven patients received a combination of fulvestrant and trastuzumab, and seven received just fulvestrant. The 14 patients in the latter groups had the option to switch to the triple-drug therapy if they didn’t respond to the treatments they received.

Every eight weeks, researchers tracked patient response through CT scans or MRIs. Those taking only fulvestrant or fulvestrant and trastuzumab showed no response at all, but about 39% of those taking the triple combination showed a partial or complete response, meaning that their tumor growth had slowed, stopped, or reversed. Those who responded continued to do so for an average of 14.4 months, with about 8.3 months free from cancer progression. Of the 14 patients who initially did not take the triple-drug combination, three of the 10 who switched to this regimen had partial responses.

Tests of the patients’ circulating tumor DNA – genetic material shed by their tumors into the bloodstream – showed that they continued to develop additional mutations in HER2 and some other cancer-related genes, which eventually caused them all to stop responding to treatment. However, the researchers say, as more therapies that target specific mutations are developed, it may be possible to treat new mutations as they arise, further extending patients’ survival.

“Circulating tumor DNA may eventually be a key component in assessing tumor evolution and providing tailored treatment,” Dr. Arteaga said.

Based in part on these results, the researchers are planning a first-in-class multi-institutional neoadjuvant trial of neratinib and the aromatase inhibitor letrozole in patients with newly diagnosed invasive lobular breast cancer harboring HER2 mutations.

Dr. Arteaga, Professor of Internal Medicine, holds The Lisa K. Simmons Distinguished Chair in Comprehensive Oncology. The Simmons Cancer Center is one of 33 members of the National Comprehensive Cancer Network and one of 56 National Cancer Institute-Designated Comprehensive Cancer Centers. The Simmons Cancer Center is ranked 19th for cancer care among over 800 cancer hospitals by U.S. News & World Report. Its faculty members treat more than 9,000 new cancer patients a year, participate in over 300 active clinical trials, and have more than $100 million in extramural cancer-focused research funding.

This study was funded in part by Puma Biotechnology Inc. and the National Cancer Institute (R01CA224899). Dr. Arteaga has served as a scientific adviser to Puma Biotechnology. Financial disclosures for all of the authors are included in the manuscript.

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 26 members of the National Academy of Sciences, 20 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

DALLAS – Oct. 24, 2023 – Recently diagnosed cancer patients often decide on their own to visit hospital emergency departments (EDs) for symptoms that don’t warrant that type of care, UT Southwestern Medical Center researchers report. Their study's results, published in the American Journal of Managed Care, could help patients safely avoid going to the ED.

“Many health system telephone answering messages advise callers that ‘if this is a medical emergency, please hang up and dial 911.’ Our findings point out that patients with cancer are often referring themselves to the ED for nonemergency issues, so they may need more directed clinical advice,” said study leader Arthur Hong, M.D., M.P.H., Assistant Professor of Internal Medicine and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern. Dr. Hong, a member of the Division of General Internal Medicine and the Harold C. Simmons Comprehensive Cancer Center, is a Texas Health Resources Clinical Scholar.

Arthur Hong, M.D., M.P.H., Assistant Professor of Internal Medicine and in the Peter O'Donnell Jr. School of Public Health at UT Southwestern, is a member of the Harold C. Simmons Comprehensive Cancer Center and a Texas Health Resources Clinical Scholar.

Cancer patients frequently experience a range of disease- and treatment-related symptoms, and those who are fearful or confused may make a default decision to go to the emergency room. However, Dr. Hong said, some of these visits can be avoided; patients may be better served visiting a cancer-specific urgent care center. Although most cancer care providers offer nurse triage phone lines 24 hours a day, seven days a week to dispense advice, it has been unclear how often patients use them to decide whether an ED visit is appropriate.

To answer this question, Dr. Hong and his colleagues evaluated data from the tumor registries of UT Southwestern and Parkland Health, a public safety-net health system for the uninsured that serves as the primary teaching hospital for UTSW. The researchers identified 39,498 adults with a new cancer diagnosis between 2012 and 2018, then compared records from these patients to those in a database of ED visits within six months of diagnosis. That database is maintained by the Dallas-Fort Worth Hospital Council Foundation, which keeps records of 12 million patients within a 100-mile radius of Dallas including details of their hospital visits.

Just over 40% of the patients made no ED visits in the six months after their diagnoses, but about 50% made one to three, and nearly 10% had four or more. Of patients who made ED visits, about 81% always self-referred, about 7% relied on medical advice at least once, and about 12% always called for triage help before an ED visit.

Although more than half of these visits ended in hospitalizations and a quarter were classified as emergencies but didn’t require hospitalization, another quarter did not require emergency care. These nonemergency visits were more likely for patients who did not consult a nurse triage line, went to the ED on weekends or holidays, or went to EDs closer to their home.

Patients who visited EDs bypassed an average of 13 that were closer to their homes. Those who visited closer EDs were no more likely to be experiencing a true medical emergency than those who traveled farther.

About half of ED visits were to centers not associated with the patient’s cancer care. That decision could lead to less personalized care recommendations and providers who may be less familiar with managing cancer- and treatment-related complications, which could affect outcomes, Dr. Hong said.

Future research should focus on why so many patients don't reach out for assistance from their clinicians to help them decide when emergency care is appropriate, he added. “Providers should take this as a signal to better address unmet patient needs,” Dr. Hong said.

UT Southwestern’s Simmons Cancer Center and Parkland Health have Acute Care clinics (Simmons Acute Care in the Cancer Care Outpatient Building and Parkland Oncology Acute Care), which provide urgent care services for patients with cancer and could help many patients avoid the ED while providing expert cancer support. The main way to access these clinics is to call a triage nurse, who can direct patients to the clinics. The research by Dr. Hong and his team should help spur additional efforts to ensure patients know about these available services.

Other UTSW researchers who contributed to this study include Amy Hughes, Ph.D., Assistant Professor in the O’Donnell School of Public Health, member of the Simmons Cancer Center, and a Texas Health Resources Clinical Scholar; D. Mark Courtney, M.D., M.S.C.I., Professor of Emergency Medicine; Hannah Fullington, M.P.H., Senior Quality Improvement Analyst; John Sweetenham, M.D., Adjunct Professor in the Simmons Cancer Center; Navid Sadeghi, M.D., Associate Professor of Internal Medicine and member of the Simmons Cancer Center; Song Zhang, Ph.D., Professor in the O’Donnell School of Public Health and member of the Simmons Cancer Center; and Angela Bazzell, D.N.P., APRN, FNP-BC, AOCNP, and Assistant Director of Advanced Practice Providers in the Simmons Cancer Center.

This study was funded by the Texas Health Resources Clinical Scholars Program, a National Cancer Institute Cancer Center Support Grant (1P30CA142543), and a Clinician Scientist Development Grant (CSDG-20-023-01-CPHPS) from the American Cancer Society. 

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 26 members of the National Academy of Sciences, 20 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

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. 16, 2023 – Combining a common chemotherapy drug with an experimental nanotechnology allowed the drug to cross the blood-brain barrier and increased the survival rate in a mouse model of glioblastoma up to 50%, a team led by researchers from UT Southwestern Medical Center and UT Dallas found. Their research, published in Nature Communications, could lead to possible new treatments for glioblastoma, the most common and aggressive primary brain tumor.

“The biggest barrier to effectively treating glioblastoma has always been getting chemotherapies into the brain. This new approach could be a game changer for this disease,” said corresponding author Robert Bachoo, M.D., Ph.D., Associate Professor of Neurology and Internal Medicine and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Zhenpeng Qin, Ph.D., Adjunct Associate Professor of Biomedical Engineering at UTSW and an Associate Professor at UT Dallas, also was a corresponding author. 

Robert Bachoo, M.D., Ph.D., Associate Professor of Neurology and Internal Medicine and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, is a corresponding author on the study. Dr. Bachoo holds the Miller Family Professorship in Neuro-Oncology.

Despite decades of research, the prognosis for glioblastoma patients remains dismal; their median survival rate is about 15 months after diagnosis. Although surgery can remove the primary tumor, glioblastoma almost universally returns due to cancerous cells that spread beyond the tumor’s visible margins. 

The biggest obstacle to killing these cells is the blood-brain barrier (BBB), proteins that form tight junctions between cells that line the brain’s blood vessels and prevent potentially toxic molecules from entering the brain. Although many chemotherapy drugs are effective against glioblastoma cells in petri dishes, Dr. Bachoo explained, the BBB prevents these drugs from reaching glioblastoma cells in patients and animal models.

Researchers have explored several strategies to open the BBB, but each has significant risks, including excessive toxicity and heat damage.

In the new study, Dr. Bachoo and his colleagues tested a new approach: gold nanoparticles coated with antibodies against a key protein in the BBB complex, a strategy they named optoBBTB. When these nanoparticles are injected intravenously in animal models, they migrate and attach to the tight junction proteins. A precise wavelength of laser light can cause these nanoparticles to vibrate, opening the BBB without generating heat.

The researchers worked with two types of genetically engineered mice that have mutations found in human glioblastoma patients and recapitulate key features of glioblastoma. When the researchers delivered optoBBTB to mice of either type, dye injected shortly afterward infiltrated the animals’ tumors, suggesting this strategy successfully breached the BBB.

Subsequent tests using the chemotherapy drug paclitaxel – also known under the brand name Taxol and used as a first-line treatment in a variety of cancers – showed it readily infiltrated the animals’ tumors after optoBBTB. After three cycles of paclitaxel treatment with optoBBTB delivered three days apart, the mouse models’ tumors shrank up to sevenfold, and the mice lived up to 50% longer compared with animals that received intravenous Taxol or a placebo.

Although these survival gains are significant, Dr. Bachoo said, the real promise behind optoBBTB is its ability to allow a variety of other promising chemotherapy drugs to be used on the brain, 98% of which cannot currently cross the BBB.

Other UTSW researchers who contributed to this study include Elizabeth Maher, M.D., Ph.D., Professor of Internal Medicine and Neurology and member of the Simmons Cancer Center, and Vamsidhara Vemireddy, M.D., Senior Research Scientist. First author Qi Cai, Ph.D., was a postdoctoral fellow in Dr. Qin’s UT Dallas laboratory.

Dr. Bachoo holds the Miller Family Professorship in Neuro-Oncology. Dr. Maher holds the Theodore H. Strauss Professorship in Neuro-Oncology.

This research was funded by the Cancer Prevention and Research Institute of Texas (CPRIT) (RP190278 and RP210236), the Department of Defense (W81XWH-21-1-0219), the American Heart Association (19CSLOI34770004), the National Institutes of Health (RF1NS110499), the National Science Foundation (2123971), and funds from a Eugene McDermott Professorship.

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 26 members of the National Academy of Sciences, 20 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.