DALLAS – April 10, 2024 – Humans aren’t the only living beings who find a singing voice attractive in the opposite sex – songbirds do too. For about a third of the approximately 4,000 songbird species that sing only one song, the features that make these tunes alluring to a potential mate have been a long-standing mystery.

Todd Roberts, Ph.D., Associate Professor of Neuroscience at UT Southwestern and a Thomas O. Hicks Scholar in Medical Research, is an Investigator in the Peter O'Donnell Jr. Brain Institute.

In a new study, researchers at UT Southwestern Medical Center used artificial intelligence (AI) to analyze the songs from zebra finches to identify qualities that indicate sexual attractiveness. Their findings, published in Nature, show that female birds detect cues in males’ songs far too intricate for the human ear to decipher.

“For decades, scientists have tried to understand how a single song could signal reproductive fitness and allow females of the species to select among male suitors. Our research suggests that female songbirds are assessing male fitness in a much more complex way than previously thought,” said Todd Roberts, Ph.D., Associate Professor of Neuroscience at UT Southwestern and a Thomas O. Hicks Scholar in Medical Research. Dr. Roberts is also an Investigator in the Peter O’Donnell Jr. Brain Institute at UTSW.

Danyal Alam, Ph.D., co-led the study while he was a graduate student in Dr. Roberts' lab.

Dr. Roberts co-led the study with Danyal Alam, Ph.D., a former graduate student in the Roberts Lab and currently a postdoctoral fellow at the University of California, San Francisco.

Zebra finches, which are often kept as pets in the U.S., are the most studied songbirds, Dr. Roberts explained. As with other songbirds, only the males sing, learning and imitating by 3 months of age the same three to seven “syllable” songs crooned by their fathers. Other research, in which scientists separated male birds from their fathers during this critical period, showed that these birds sing improvised songs. However, birds that sing these makeshift tunes are less likely to attract a mate, suggesting females prefer mates that imitate songs over those that improvise them.

Zebra finches, which are often kept as pets in the U.S., are the most studied songbirds.

Building on this research, Dr. Alam developed an AI program he named the Deep Avian Network (DAN), which analyzed the acoustic features of the songs of 49 zebra finches in the Roberts Lab. About half of these birds sang songs imitated from their fathers, and the other half sang improvised songs. Using data from nearly half a million syllables, DAN clustered those that shared features onto a visual map.

When the researchers analyzed the maps, they found the path between the clusters to be significantly longer for imitated songs than for improvised ones, indicating the imitated songs had more complexity, although this intricacy was indistinguishable to humans, Dr. Roberts said.

To determine whether this complexity was more attractive to female zebra finches, the researchers developed synthetic songs with features of the longer- and shorter-path songs. They then allowed female birds to fly freely in a simple T-shaped maze and played the contrasting songs at opposite ends. Females spent significantly more time in the end where the longer-path (imitated) song was played, a sign that they found it more appealing.

The researchers, seeking to learn why these songs might signal sexual fitness, used DAN to analyze imitated songs from fathers and their offspring. Although offspring readily imitated songs with syllables that clustered in shorter paths, those whose fathers sang more complex songs were less likely to faithfully replicate these features, an indication that these songs were more difficult to learn.

Having the resources and mental acuity to learn these more difficult songs might be more attractive to potential mates, Dr. Roberts explained. He and his colleagues plan to test in a future study whether birds that sing more complicated songs, as determined by DAN, are more likely to produce offspring than those singing simpler songs – the real test of reproductive fitness.

Fayha Zia, a former undergraduate researcher in the Roberts Lab, also contributed to this study.

Dr. Alam was funded by a prestigious Diversity Specialized Predoctoral to Postdoctoral Advancement in Neuroscience (D-SPAN) Award from the National Institutes of Health.

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.

Lukasz Joachimiak, Ph.D., Associate Professor in the Center for Alzheimer's and Neurodegenerative Diseases and of Biochemistry at UT Southwestern, is an Effie Marie Cain Scholar in Medical Research and an Investigator in UTSW's Peter O'Donnell Jr. Brain Institute.

“Now that we know more about how these oligomeric chaperones work, we could potentially tailor them to be more specific for disease proteins so they’ll work even better,” said study leader Lukasz Joachimiak, Ph.D., Associate Professor in the Center for Alzheimer’s and Neurodegenerative Diseases and of Biochemistry at UT Southwestern. Dr. Joachimiak, an Effie Marie Cain Scholar in Medical Research, is an Investigator in UTSW’s Peter O’Donnell Jr. Brain Institute.

All proteins are produced in the body in a linear chain, made of amino acid building blocks sequentially strung together. But to perform their diverse roles in the body, these chains need to fold into precise shapes. While some chaperones sculpt proteins into these folded conformations at the ribosomes, which are the cells’ protein production factories, others like DNAJB8 scour cells for misfolded proteins and either correct their conformation or send them elsewhere in cells for further processing. By steering misfolded proteins back into the correct conformation, DNAJB8 and some other oligomeric chaperones prevent misfolded proteins from intertwining and forming clumps that cause many degenerative and neurodegenerative diseases. They become key gatekeepers to prevent the diseases from starting.

Scientists have long known that DNAJB8 can exist both as individual units, called monomers, or as an assembly of monomers known as an oligomer. Previous studies showed that mutating these proteins in various ways prevented assembly into oligomers and stopped their ability to correct misfolded proteins. However, the exact part of DNAJB8 that’s necessary for assembly into oligomers was unknown, and the role of its monomers was unclear.

“We needed to decouple the ability of this chaperone to assemble from its ability to prevent misfolding of proteins,” Dr. Joachimiak explained.

To do this, the researchers mutated individual amino acids that make up DNAJB8. They found that swapping a single amino acid known as phenylalanine 151 to a different amino acid prevented DNAJB8 from forming oligomers both in a test tube and in cells.

Using this altered form of DNAJB8 that stayed in monomeric form, Dr. Joachimiak and his colleagues showed that these monomers readily bound to and reshaped misfolded tau protein – a causative agent in Alzheimer’s disease – but did not affect correctly folded tau. The same was true for misfolded Htt, the protein involved in Huntington’s disease. These findings suggest that the monomers, rather than the oligomers, are the active component in correcting misfolded proteins.

One theory is that the oligomer serves as a storage depot for monomers, which do the real work of suppressing protein misfolding. It’s an idea that the Joachimiak Lab will test in future studies. Dr. Joachimiak and his colleagues also plan to test whether further altering these monomers could make them useful for diagnosing diseases marked by protein misfolding or more effective in correcting misfolding in specific proteins for use as possible therapies.

Other UTSW researchers who contributed to this study include first author Bryan D. Ryder, Ph.D., former graduate student researcher in the Joachimiak Lab; Marc I. Diamond, M.D., Director of the Center for Alzheimer’s and Neurodegenerative Diseases and Professor of Neurology and Neuroscience; Ayde Mendoza-Oliva, Ph.D., Instructor in the Center for Alzheimer’s and Neurodegenerative Diseases and of Biochemistry; and Joachimiak Lab members Pawel M. Wydorski, M.S., graduate student researcher, Paulina Macierzynska, M.S., graduate student assistant, and Nabil Morgan, Research Technician.

This study was funded in part by National Institutes of Health (NIH) grants (RF1AG065407 and RF1AG078888) with work performed at the Electron Microscopy Core Facility at UTSW, which is also supported by NIH grants (1S10OD021685-01A1 and 1S10OD020103-01).

Dr. Diamond holds the Effie Marie Cain Distinguished University Chair in Alzheimer’s Research.

About UT Southwestern Medical Center  

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 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 27, 2024 – A gene therapy developed by researchers at UT Southwestern Medical Center for a rare disease called giant axonal neuropathy (GAN) was well tolerated in pediatric patients and showed clear benefits, a new study reports. Findings from the phase one clinical trial, published in the New England Journal of Medicine, could offer hope for patients with this rare condition and a host of other neurological diseases.

“This trial was the first of its kind, for any disease, using an approach to broadly deliver a therapeutic gene to the brain and spinal cord by an intrathecal injection,” said co-author Steven Gray, Ph.D., Associate Professor of Pediatrics, Molecular Biology, Neurology, and in the Eugene McDermott Center for Human Growth and Development at UT Southwestern. “Even with the relatively few patients in the study, there were clear and statistically significant benefits demonstrated in patients that persisted for years.”

Dr. Gray developed this gene therapy with co-author Rachel Bailey, Ph.D., Assistant Professor in the Center for Alzheimer’s and Neurodegenerative Diseases and of Pediatrics at UTSW. Dr. Gray is an Investigator in the Peter O’Donnell Jr. Brain Institute.

GAN is extraordinarily rare, affecting only about 75 known families worldwide. The disease is caused by mutations in a gene that codes for a protein called gigaxonin. Without normal gigaxonin, axons – the long extensions of nerve cells – swell and eventually degenerate, leading to cell death. The disease is progressive, typically starting within the first few years of a child’s life with symptoms including clumsiness and muscle weakness. Patients later lose the ability to walk and feel sensations in their arms and legs, and many gradually lose hearing and sight and die by young adulthood.

In the clinical trial conducted at the National Institutes of Health (NIH), Drs. Gray and Bailey worked with colleagues from the National Institute of Neurological Disorders and Stroke (NINDS) to administer the therapy to 14 GAN patients from 6 to 14 years old. Using a technique they developed to package the gene for gigaxonin into a virus called adeno-associated virus 9 (AAV-9), the researchers injected it into the intrathecal space between the spinal cord and the thin, strong membrane that protects it. Tested for the first time for any disease, this approach enabled the virus to infect nerve cells in the spinal cord and brain to produce gigaxonin in nerve cells, allowing them to heal the cells’ axons, which grow throughout the body.

Amanda Grube, 14, one of the trial's participants, has seen improvement in her diaphragm and other muscles associated with breathing, her mother says. However, many of Amanda's other functions, including her mobility, did not benefit. (Photo credit: McKee family)

After one injection, the researchers followed the patients over a median of nearly six years to determine whether the treatment was safe and effective. Only one serious adverse event was linked to the treatment – fever and vomiting that resolved in two days – suggesting it was safe. Over time, some patients showed significant recovery on an assessment of motor function. Other measurements revealed that several of the patients improved in how their nerves transmitted electrical signals.

One of the trial’s participants, 14-year-old Amanda Grube, has experienced improvement in her diaphragm and other muscles associated with breathing, according to her mother, Katherine McKee. However, many of Amanda’s other functions did not benefit – including her mobility.

“That’s why I hope there’s more to come from the research that can help patients even more,” Mrs. McKee said. “Amanda has dreams and ambitions. She wants to work with animals, save the homeless, and design clothes for people with disabilities.” 

Dr. Gray said that in many ways, the study offers a road map to carry out similar types of clinical trials. “The findings have broader implications because this study established a general gene therapy treatment approach that is already being applied to dozens more diseases,” he said.

Although the phase one results are promising, Dr. Gray said he and other researchers will continue to fine-tune the treatment to improve results in future GAN clinical trials. He is also using this method for delivering gene therapies to treat other neurological diseases at UTSW, where he is Director of the Translational Gene Therapy Core, and at Children’s Health. Work in the Gray Lab has already led to clinical trials for diseases including CLN1 Batten disease, CLN5 Batten disease, CLN7 Batten disease, GM2 gangliosidosis, spastic paraplegia type 50, and Rett syndrome.

The GAN study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), Division of Intramural Research, NIH; Hannah’s Hope Fund; Taysha Gene Therapies; and Bamboo Therapeutics-Pfizer.

Drs. Bailey and Gray are entitled to royalties from Taysha Gene Therapies. Dr. Gray has also consulted for Taysha and serves as Chief Scientific Adviser.

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 20, 2024 – Surgical nerve decompression, used to treat conditions such as carpal tunnel syndrome and sciatica, could play a role in relieving the pain of diabetic neuropathy patients, researchers at UT Southwestern Medical Center found.

Study leader Shai Rozen, M.D., is Professor and Vice Chair of Plastic Surgery at UT Southwestern.

The five-year study, published in the Annals of Surgery, was the first randomized control trial to assess the effectiveness of lower extremity nerve decompression surgery on patients with diabetic peripheral neuropathy.

Approximately 20 million Americans suffer from diabetic neuropathy, a progressive condition that damages the nerves, primarily in the legs and feet. The primary treatment today is the use of temporary pain-relieving medications, but many patients find them ineffective after prolonged use.

“Diabetic neuropathy can be debilitating, leading to a lack of mobility and a severe reduction in quality of life,” said study leader Shai Rozen, M.D., Professor and Vice Chair of Plastic Surgery. “It’s believed that roughly one-third of those with neuropathy pain have nerve compression – where there is direct and chronic pressure on a peripheral nerve – due to physiological changes brought on by diabetes. Our research suggests that nerve decompression surgery to release compressed nerves from surrounding tissue could offer lasting relief for those individuals.”

In diabetic neuropathy, nerves can swell and eventually be compressed by surrounding semirigid tissue, causing pain, muscle weakness, or both. In the surgery, the semirigid tissue is removed from the swollen nerve, allowing for improved blood flow to relieve symptoms. 

The study followed 78 patients at UT Southwestern and Parkland Health who were randomly placed into two groups – one receiving surgery and one serving as an observation group who remained on medication only. Those selected for surgery also had one leg randomly chosen for “sham surgery” – when the surgeon makes incisions to mimic the procedure but without principal therapeutic actions (i.e., nerve release) – while the other leg underwent nerve decompression.

Patients agreed to being blinded about which leg underwent sham surgery and which had decompression surgery. Additionally, the evaluators were blinded regarding which group the patients were in. “This masking of patients and evaluators further increases the reliability of the results,” Dr. Rozen said.

During follow-up visits, patients completed standard pain and lifestyle questionnaires. At the 12-month visit, the patients who underwent surgical intervention reported significantly less pain in both legs, while the observation group's pain rankings were unchanged.

At 56 months, under the same patient- and evaluator-blinded conditions, the surgical group reported even greater pain reduction, while the observation group had worse pain. Unlike the 12-month follow-up, however, surgical patients reported far more improvement in their decompressed legs than in their sham surgery legs.

“The one-year reports of pain improvement in both legs could mean that there is a placebo effect taking place, but the five-year results suggest that the procedure actually does have a positive long-term impact on pain,” Dr. Rozen said. “There is still much debate in the medical community about the value of decompression surgery in treating diabetic neuropathy, and while this study doesn’t settle the issue, it should help expand the discourse among stakeholders and hopefully lead to even more research. The goal is to better understand the efficacy of nerve decompression surgery on diabetic neuropathy and improve our ability to identify patients who are likely to respond to surgical intervention.” 

Other UTSW researchers who contributed to the study are Steven Vernino, M.D., Ph.D., Professor of Neurology; Philip Raskin, M.D., Professor of Internal Medicine in the Division of Endocrinology; Linda Hynan, Ph.D., Adjunct Professor in the Peter O’Donnell Jr. School of Public Health and of Psychiatry; April Gorman, Ph.D., Biostatistician, O’Donnell School of Public Health; and Rita Fulmer, M.S.N., APRN, FNP-C, Physical Medicine & Rehabilitation.  

Dr. Vernino is a Distinguished Teaching Professor and holds the Dr. Bob and Jean Smith Foundation Distinguished Chair in Neuromuscular Disease Research and the Rex Griswold Distinguished Professorship in Multiple System Atrophy. He also serves as Vice Chair for Education and Faculty Affairs and is an Investigator in the Peter O’Donnell Jr. Brain Institute. Dr. Raskin holds the Clifton and Betsy Robinson Chair in Biomedical Research. 

This study was funded by the National Institutes of Health (UL1TR001105) and the David M. Crowley Foundation.

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 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 – Feb. 13, 2024 – Results from phase two clinical trials at UT Southwestern Medical Center showed that a suspension of gold nanocrystals taken daily by patients with multiple sclerosis (MS) and Parkinson’s disease (PD) significantly reversed deficits of metabolites linked to energy activity in the brain and resulted in functional improvements. The findings, published in the Journal of Nanobiotechnology, could eventually help bring this treatment to patients with these and other neurodegenerative diseases, according to the authors.

Peter Sguigna, M.D., Assistant Professor of Neurology and Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern, leads the active multiple sclerosis clinical trial.

“We are cautiously optimistic that we will be able to prevent or even reverse some neurological disabilities with this strategy,” said Peter Sguigna, M.D., who leads the active MS trial and is an Assistant Professor of Neurology and an Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern.

Healthy brain function depends on a continuous supply of energy to this organ’s cells through a molecule called adenosine triphosphate (ATP), Dr. Sguigna explained. Age causes a decline in brain energy metabolism, evident in a decrease in the ratio of nicotinamide adenine dinucleotide (NAD⁺) and its partner, nicotinamide adenine dinucleotide + hydrogen (NADH).

However, studies have shown that in neurodegenerative conditions such as MS, PD, and amyotrophic lateral sclerosis (ALS) – also known as Lou Gehrig’s disease – this decline in the NAD⁺/NADH ratio is much faster and more severe. Studies in cells, animal models, and human patients have suggested that halting or reversing this energy deficit could lead to a slower decline or even partial recovery for patients with neurodegenerative diseases, Dr. Sguigna said.

Toward that end, he and his colleagues partnered with Clene Nanomedicine, a company developing gold nanocrystals into an orally administered therapeutic agent for neurodegenerative conditions, including an experimental treatment named CNM-Au8. These nanocrystals act as catalysts that improve the NAD⁺/NADH ratio, positively altering brain cells’ energy balance – a phenomenon demonstrated in cellular and animal models in previous studies.

To determine whether CNM-Au8 was reaching its intended target in human patients, the UTSW researchers recruited 11 participants with relapsing MS and 13 with Parkinson’s for two phase two clinical trials, REPAIR-MS and REPAIR-PD. These participants received an initial brain magnetic resonance (MR) spectroscopy scan to determine their baseline NAD⁺/NADH ratio and the levels of other molecules associated with cell energy metabolism. After they took a daily dose of CNM-Au8 for 12 weeks, testing included a second MR spectroscopy.

Together, the 24 patients had an average increase in their NAD⁺/NADH ratios of 10.4% compared with baseline, showing that CNM-Au8 was targeting the brain as intended. Other energetic molecules, including ATP, normalized to the group mean by the end of treatment, another potentially beneficial effect. Using a validated survey for functional outcomes in PD, researchers found that study patients with this condition reported improved “motor experiences of daily living” at one point, suggesting that taking CNM-Au8 could ameliorate functional symptoms of their disease. None of the patients experienced severe adverse side effects linked to CNM-Au8.

While these results are encouraging, additional studies are needed, Dr. Sguigna said. REPAIR-MS will continue to enroll participants to see whether similar findings can be reproduced in progressive MS.

Other UTSW researchers who contributed to this study were Jimin Ren, Ph.D., Associate Professor of Radiology and in the Advanced Imaging Research Center, the study’s first author who led the MR spectroscopy portion of the research, and Benjamin Greenberg, M.D., Professor of Neurology and Pediatrics, Vice Chair of Clinical and Translational Research, a Cain Denius Scholar in Mobility Disorders, and a Distinguished Teaching Professor.

Dr. Sguigna cited support he received from the Physician Scientist Training Program (PSTP) and President’s Research Council at UT Southwestern.

When the trials were conducted, Dr. Greenberg was solely affiliated with UTSW. He was employed by Clene Nanomedicine as a consultant after the conclusion of part one of REPAIR-MS.

This study was funded by Clene Nanomedicine.

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. 06, 2024 – UT Southwestern Medical Center researchers have identified an experimental molecular compound that improved survival among cellular models and mouse models of amyotrophic lateral sclerosis (ALS), the fatal neurodegenerative disease. Their findings, reported in Cell Death & Disease, offer promise for the potential development of treatments for ALS, which has no effective therapy.

“This study will significantly advance the ALS field by providing a leading compound and a signaling pathway for future investigations,” said study leader Chun-Li Zhang, Ph.D., Professor of Molecular Biology and a W.W. Caruth, Jr. Scholar in Biomedical Research at UT Southwestern. Dr. Zhang is also an Investigator in the Peter O’Donnell Jr. Brain Institute at UTSW.

ALS, also known as Lou Gehrig’s disease, affects hundreds of thousands worldwide. With onset in midlife, ALS kills motor neurons over time, gradually depriving patients of the ability to walk, talk, swallow, and breathe. Life expectancy is two to five years after diagnosis and hasn’t changed despite decades of research, Dr. Zhang explained.

Searching for potential therapies that might extend the lives of ALS patients, Dr. Zhang and his colleagues tested compounds from a pharmaceutical library on a cellular model of ALS. Because it is impossible to sample motor neurons directly from ALS patients, previous studies have largely used neurons that were derived from pluripotent stem cells. However, Dr. Zhang said, these neurons were reset to an embryonic stage, losing age-related changes.

This image shows Hit3-treated human amyotrophic lateral sclerosis (ALS) neurons cultured in the lab of Dr. Chun-Li Zhang.

For the new study, the researchers used a different approach that converted ALS patients’ skin cells into motor neurons that bore marks of aging, providing a more realistic model. After dosing these cells with about 2,000 compounds, the researchers identified a promising one they dubbed Hit3. This compound reversed some of the cells’ ALS-related morphological changes, causing them to grow larger cell bodies, develop more complicated branching in their extensions, form more connections with muscle cells, and live significantly longer than cells that didn’t receive Hit3.

A closer look showed that Hit3 acts on cell proteins called MAP4Ks, which play key roles in cells’ responses to stress. Once activated, MAP4Ks regulate a cascade of other proteins involved in this role, a molecular pathway that appears critical in deciding whether motor neurons live or die and has been implicated in ALS and other neurodegenerative diseases.

To determine what effect manipulating this pathway could have on ALS animal models, the researchers dosed mice that had mutations in a gene called SOD1 – considered the most aggressive form of ALS – with a compound related to Hit3 called MAP4Ki. Mice that didn’t receive this compound had a dramatic loss of motor neurons and died at an average of 129 days. However, mice that received MAP4Ki maintained significantly more motor neurons and lived 10 days longer.

“Even though MAP4Ki extended survival by just a short time, our results suggest treatments that block the MAP4K pathway could one day be useful therapeutically,” Dr. Zhang said.

Because MAP4Ki isn’t optimized for pharmaceutical use – it degrades quickly and can’t cross the blood-brain barrier, limiting its absorption – this compound has significant room for chemical manipulations that could improve its activity, Dr. Zhang said. In addition, he noted, because targeting the MAP4K pathway has shown promise, researchers could eventually develop other drugs designed to affect this pathway more successfully. The hope is that this could potentially extend ALS patients’ life span.

Other UTSW researchers who contributed to this study were Shuaipeng Ma, Ph.D., Research Scientist; Wenjiao Tai, M.D., Ph.D., Instructor of Molecular Biology; Xiaoling Zhong, Ph.D., Research Scientist; and Yuhua Zou, M.Sc., Research Scientist, all members of the Zhang Lab.

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. 11, 2024 – A study of mutant models of fragile X syndrome (FXS), a genetic disorder related to autism and intellectual disability, shows that activation of the cerebellum mitigates aberrant responses in sensory processing areas of the brain and improves neurodevelopmental behaviors. The findings, published by UT Southwestern Medical Center researchers in Cell Reports, could offer an opportunity for developing new therapies for neurocognitive disorders. 

Peter Tsai, M.D., Ph.D., is Associate Professor of Neurology, Neuroscience, Pediatrics, and Psychiatry at UT Southwestern. He is also an Investigator in the Peter O'Donnell Jr. Brain Institute.

“This study has important clinical implications because, while the majority of people affected by neurocognitive illness have symptoms elsewhere in the brain other than the cerebellum, treating the cerebellum specifically could be sufficient to produce improvement,” said Peter Tsai, M.D., Ph.D., Associate Professor of Neurology, Neuroscience, Pediatrics, and Psychiatry at UT Southwestern. Dr. Tsai is an Investigator in the Peter O’Donnell Jr. Brain Institute.

UTSW researchers examined the contributions of the cerebellum to FXS, building on their previous research on the role of the cerebellum in autism spectrum disorders (ASD). FXS is linked to high rates of ASD, accounting for up to 2% of all ASD cases. The disorder, which results in challenges and impairments in social behaviors, cognitive function, and sensory hypersensitivity, is caused by silencing of the fragile X messenger ribonucleoprotein 1 (Fmr1) gene in FXS.

The new study found that mice lacking Fmr1 in cerebellar output neurons had impaired social behaviors. The cerebellar Fmr1-deficient mice were less interested in social stimuli and had heightened sensory hypersensitivity in audible startle testing.

Mice lacking Fmr1 throughout the body also had similar social impairments, sensory hypersensitivity, and learning challenges. However, researchers found that reintroducing the gene only into neurons in the cerebellum in these global Fmr1 mutant mice resulted in improved behavior and learning as well as reduced sensitivity to sensory stimulation as compared with mice lacking Fmr1 globally including within the cerebellum.

In addition, researchers found that reintroducing the gene only into neurons in the cerebellum in the global Fmr1 mutant mice restored normal levels of neuron excitability within the cortex. Fixing the hyperactivity in the cortex has been linked to improvement in cases where Fmr1 is missing, and thus cerebellar expression might influence neurodevelopmental behaviors through this mechanism. “It is striking that genetic reintroduction of Fmr1 just in the cerebellum leads to improved physiological function in other brain regions, even though the gene is still missing in those regions,” Dr. Tsai said.

Having established the impact of both cerebellar-specific and global Fmr1 mutants on neurodevelopmental behaviors, the researchers investigated the effects of cerebellar modulation. They found that stimulating the function of cerebellar output neurons in a specific cerebellar region known to have important roles in neurodevelopmental behaviors could improve impaired sociability, learning, and sensory behaviors. 

“Given the cerebellum’s role in interacting with other brain regions, modulating or influencing the cerebellum could potentially offer clinical benefits for individuals with neurodevelopmental challenges,” Dr. Tsai said, emphasizing the clinical importance of this finding. 

Other UTSW researchers who contributed to this study are first author Jennifer Gibson, B.A., graduate student; Anthony Hernandez Vazquez, B.S., graduate student; Kunihiko Yamashiro, Ph.D., postdoctoral researcher; Vikram Jakkamsetti, M.D., Ph.D., Instructor of Neurology; Chongyu Ren, M.D., Ph.D., Research Scientist; Katherine Lei, B.A., medical student; Brianne Dentel, B.S., graduate student; and Juan Pascual, M.D., Ph.D., Professor of Neurology and Pediatrics.

Dr. Pascual holds the Ed and Sue Rose Distinguished Professorship in Neurology and The Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases.

This research was funded by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (K08NS083733, NS102588, and NS077015), National Institute of Mental Health of the NIH (R01MH116882 and R01MH120069-01A1), the National Heart, Lung, and Blood Institute (1T32HL139438-01A1), and the Sleep and Circadian Rhythms Training Program (T32HL139438).

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. 08, 2024 – An increased concentration of the hormone leptin in fat cells is believed to be responsible for weight gain associated with antipsychotic drugs, according to research led by UT Southwestern Medical Center. The study, published in Science Translational Medicine, used a mouse model to uncover the underlying mechanisms of unwanted metabolic side effects and to test an antibody that might reduce them.

Despite the effectiveness of antipsychotic drugs in managing psychiatric conditions, prescriptions such as olanzapine and risperidone can cause patients to add significant weight and in some cases result in diabetes and liver disease.

Philipp Scherer, Ph.D., Professor of Internal Medicine and Director of the Touchstone Center for Diabetes Research at UT Southwestern, holds the Gifford O. Touchstone, Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research and the Touchstone/West Distinguished Chair in Diabetes Research.

“Weight gain affects most patients who start taking these antipsychotic drugs and is a well-established side effect of these interventions. As a result, many individuals become insulin resistant and diabetic. The study implicates leptin as a key driver of these negative metabolic consequences,” said Philipp Scherer, Ph.D., Professor of Internal Medicine and Director of the Touchstone Center for Diabetes Research at UT Southwestern.

Patients using antipsychotic drugs experience increased concentrations of circulating leptin released from fat cells before they begin to gain weight. Prior to this study, however, it was not well understood how increased leptin, or hyperleptinemia, was connected to this drug-induced weight gain.

“While it was historically viewed as a ‘passenger’ to obesity – meaning levels go up as we gain weight – our data strongly suggest that it is a ‘driver’ for drug-induced obesity,” Dr. Scherer explained.

Using a previously tested mouse model, researchers obtained evidence that hyperleptinemia was directly contributing to obesity and issues such as liver fibrosis, insulin resistance, and untimely mammary duct development. Moreover, researchers found that hyperleptinemia increased inflammation, which is considered a main contributor in the development of antipsychotic drug-induced metabolic disorders.

Results also indicated that treating mice with a leptin-neutralizing antibody greatly reduced the side effects. Treatment with the antibody led to reduced weight gain, inflammation, and mammary gland development as well as improved glucose tolerance in mice with drug-induced side effects. These key findings provide a path toward improving outcomes for patients in the future.

“We are working hard to take the leptin-neutralizing antibodies that we have used here into a clinical setting to find out whether the mechanisms defined in rodents also apply to individuals who embark on an antipsychotic treatment regimen,” Dr. Scherer noted.

Other UTSW researchers who contributed to this study include co-first authors Shangang Zhao, Ph.D., former postdoctoral researcher, and Qian Lin, Ph.D., postdoctoral fellow, both in the Touchstone Center; Joel K. Elmquist, D.V.M., Ph.D., Professor of Internal Medicine, Pharmacology, and Psychiatry, Director of the Center for Hypothalamic Research, and Vice Chair of Research for Internal Medicine; Associate Professor Chen Liu, Ph.D., Assistant Professors May-Yun Wang, Ph.D., and Christine M. Kusminski, Ph.D., Instructors Qingzhang Zhu, Ph.D., and Chao Li, Ph.D., and Assistant Instructor Steven C. Wyler, Ph.D., all of Internal Medicine; Li Li, Ph.D., postdoctoral research fellow at the Center for Hypothalamic Research; Leon Straub, Ph.D., and Jan-Bernd Funcke, Ph.D., both postdoctoral fellows in the Touchstone Center; Xue-Nan Sun, Ph.D., postdoctoral fellow in the Oh Lab; and Shiuhwei Chen, M.S., Senior Research Associate at the Touchstone Center.

Drs. Elmquist and Liu are Investigators with the Peter O’Donnell Jr. Brain Institute.

Dr. Scherer holds the Gifford O. Touchstone, Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research and the Touchstone/West Distinguished Chair in Diabetes Research. Dr. Elmquist holds the Carl H. Westcott Distinguished Chair in Medical Research and the Maclin Family Distinguished Professorship in Medical Science, in Honor of Dr. Roy A. Brinkley. Dr. Zhao holds a Voelcker Fund Young Investigator Pilot Award from the Max and Minnie Tomerlin Voelcker Fund.

This study was funded by grants from the National Institutes of Health (R01-DK55758, R01-DK099110, RC2-DK118620, R01-DK127274, R01-DK131537, P01-AG051459, R01-DK118725, R01-DK088423, R01 DK114036, DK130892, and R00-AG068239), Cancer Prevention and Research Institute of Texas (RP190561), American Heart Association (23POST1019715 and 855170), and funding from the UT Southwestern Nutrition Obesity Research Center under the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institutes of Health (P30-DK127984).

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. 18, 2023 – While the holiday season can bring joy to people of all ages, it also leaves many feeling depressed and lonely. Those who already suffer from a mental health condition can develop more serious symptoms. According to a survey by the National Alliance on Mental Illness (NAMI), 64% of people who have mental illness say their symptoms become worse when the winter holidays arrive.

Manish Jha, M.D., Associate Professor of Psychiatry, is a member of the Peter O'Donnell Jr. Brain Institute at UT Southwestern and an O'Donnell Clinical Neuroscience Scholar.

To avoid the “holiday blues,” a psychiatrist at UT Southwestern Medical Center recommends building resilience against factors that can lead to depression and consulting with your primary care provider if isolation brings on despondent feelings during the holidays.

“Helpful strategies include adding more exercise to the daily routine, ensuring that sleep hygiene is not disrupted, refraining from excessive alcohol intake, and avoiding extreme or problematic use of social media,” said Manish Jha, M.D., Associate Professor of Psychiatry, a member of the Peter O’Donnell Jr. Brain Institute, and an O’Donnell Clinical Neuroscience Scholar.

According to NAMI, the holiday blues are temporary symptoms of anxiety or depression that can be linked to the added stress of the holidays, unrealistic expectations, sentimental memories, and feelings of loss. They can cause sadness, distress, fatigue, tension, frustration, and loneliness.

NAMI suggests several ways to avoid the holiday blues:

• Stick to normal routines as much as possible.
• Take time for yourself, but don’t isolate. Spend time with supportive, caring people.
• Make a to-do list. Keep things simple.
• Listen to music or find other ways to relax.
• Set reasonable goals for activities such as shopping, cooking, entertaining, attending parties, or sending cards.
• Make a budget for activities. Don’t overextend financially on gift-giving.

Dr. Jha said reduced daylight contributes to seasonal affective disorder, a type of depression that is usually worse during the winter. He also said an inability to be with family can produce symptoms of depression, and holiday changes in eating habits can affect mood and lead to weight gain.

While the holidays may cause some symptoms of depression, Dr. Jha said it’s important to get a clinical evaluation to ensure that signs of major depressive disorder (MDD) are not overlooked. Although the holiday blues generally don’t linger, they should be taken seriously because they can lead to long-term mental health conditions. He added that MDD affects an estimated 1 in 5 adults in the United States and often goes undiagnosed, so screening for depression is crucial.

“The U.S. Preventive Services Task Force recommends screening for depression in adults,” Dr. Jha said. “Providers can use easy-to-administer measures to screen for symptom severity that may indicate the presence of a depressive disorder.”

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.

Madhukar Trivedi, M.D., Professor of Psychiatry at UT Southwestern, holds the Betty Jo Hay Distinguished Chair in Mental Health and the Julie K. Hersh Chair for Depression Research and Clinical Care.

Hundreds of patients will participate in the trials at UT Southwestern and other sites across the country, making them the largest trials ever conducted for this purpose, said Principal Investigator Madhukar Trivedi, M.D., Professor of Psychiatry.

“Prevalence of methamphetamine and cocaine use disorders continues to increase, and there are no treatments approved by the U.S. Food and Drug Administration for either of these conditions. These studies could offer the first medical treatments for individuals suffering from stimulant addictions and help them regain control over their lives,” said Dr. Trivedi, an Investigator in the Peter O’Donnell Jr. Brain Institute and founding Director of the Center for Depression Research and Clinical Care at UT Southwestern.

An estimated 1.6 million people over age 12 in the U.S. have methamphetamine use disorder (MUD) and 1.4 million have cocaine use disorder (CUD), according to NIDA. Tens of thousands die from these chronic conditions each year, and those who survive typically have vast disruptions in their social relationships, work, and other aspects of daily life.

The three studies, funded at a total of nearly $30 million, are evaluating the effectiveness of drugs and other therapies for the conditions. They include:

• A randomized, double-blind, placebo-controlled trial to test injections of extended-release naltrexone every three weeks and extended-release buprenorphine every four weeks for people with CUD. Naltrexone is prescribed for opioid use disorder and alcohol use disorder. A combination similar to this that used injections of extended-release naltrexone and oral sustained-release bupropion showed promise for patients with MUD in a study by Dr. Trivedi and colleagues published in 2021 in the New England Journal of Medicine.
• A trial to test the feasibility and efficacy of transcranial magnetic stimulation for patients with either MUD or CUD. The procedure uses magnetic fields to stimulate cortical regions of the brain.
• A trial comparing the feasibility, efficacy, and safety of intravenously delivered ketamine (an anesthetic) versus midazolam (a sedative) in patients with MUD.

A fourth study, expected to begin next year, is a randomized, double-blind, placebo-controlled trial to test the efficacy of extended-release naltrexone plus bupropion XL compared with matched injectable and oral placebo in reducing methamphetamine use in individuals with moderate or severe MUD. This study is being done to replicate the findings from Dr. Trivedi’s 2021 study.

Dr. Trivedi has also received funding from NIDA for several smaller trials focused on other aspects of substance use disorders. These include a study aimed at developing new approaches to recruit Black patients with substance abuse disorders for clinical trials to reduce health disparities; a study exploring a potential method to supervise patients who take methadone at home to treat opioid abuse disorder; and a study assessing the feasibility of web-based software to help primary care physicians screen, diagnose, and prescribe treatments for opioid abuse disorder.

“Substance abuse disorders bring immense bias and stigma, but they are medical conditions that need treatments,” Dr. Trivedi said. “These trials may result in treatments that can truly help patients.”

Dr. Trivedi holds the Betty Jo Hay Distinguished Chair in Mental Health and the Julie K. Hersh Chair for Depression Research and Clinical Care. Dr. Trivedi also has served as a consultant to companies that develop treatments for substance abuse disorders.

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.

Maria Chahrour, Ph.D., Associate Professor in the Eugene McDermott Center for Human Growth and Development and the Center for the Genetics of Host Defense at UT Southwestern, is also an Investigator in the Peter O’Donnell Jr. Brain Institute.

“This study is one of the few that provides a mechanistic understanding of autism spectrum disorder,” said senior author Maria Chahrour, Ph.D., Associate Professor of Neuroscience and Psychiatry and an Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern.  

About 1 of every 36 children in the United States is diagnosed with ASD, according to the Centers for Disease Control and Prevention. Underscoring the significant role of genetics in ASD, Dr. Chahrour noted that twin studies suggest about 90% heritability. Although hundreds of genes associated with ASD have been identified, she added, how these genes might contribute to the disorder is largely unknown.

In 2020, Dr. Chahrour and her colleagues discovered an ASD-associated gene called KDM5A, showing that patients carrying mutations in this gene typically have ASD, lack of speech, intellectual disability, and other symptoms. Although KDM5A is known to encode a chromatin regulator – a protein that affects how DNA is packaged in cells and whether other genes are expressed – the mechanism behind its role in ASD was unknown.

Knowing that chromatin regulators affect cell identity, or how cells develop into specific types, Dr. Chahrour and her colleagues delved into the assortment of cell types in a mouse model in which this gene had been eliminated. They looked specifically at the brain’s center of learning and memory, the hippocampus, the structure and function of which is altered in ASD.

This image, obtained from a mouse brain using a brightfield microscope, shows the richly diverse cells of the hippocampus pseudocolored with different hues. Maria Chahrour, Ph.D., and colleagues investigated how cells in the hippocampus are affected in autism spectrum disorder, showing that unique subtypes of excitatory and inhibitory neurons are particularly vulnerable upon loss of an autism gene and chromatin regulator.

The hippocampus has four main cell types – excitatory neurons, inhibitory neurons, glia, and endothelial cells – and these four are further divided into 24 subtypes. Using a technique known as single-nuclei RNA sequencing, the researchers sequenced more than 105,000 nuclei to compare the populations of cell types present in the hippocampus among mice with KDM5A and mice without the gene, or “knockouts.”

Their analysis showed distinct differences in four subtypes of excitatory neurons and two subtypes of inhibitory neurons. In the mice without KDM5A, some of these cell types increased in number, some decreased, and one switched to a different subtype within its class, suggesting KDM5A plays an important part in determining cell identity during development.

A closer look at the cells in the KDM5A knockout animals’ hippocampi showed cells in this area appeared more mature, with abnormally more and longer branching cells than in animals with KDM5A. Many of the affected cells resided in a region of the hippocampus known as CA1, key for storing social memories, or recollections of interactions with others. The changes in cell types can result in imbalances of excitation and inhibition, and the defects in cellular development can damage hippocampal circuits and lead to dysfunction of the hippocampus, accounting for some of the symptoms associated with ASD, Dr. Chahrour said.

Dr. Chahrour, who is also an Associate Professor in the Eugene McDermott Center for Human Growth and Development and the Center for the Genetics of Host Defense at UTSW, said these findings further the vital mission of her lab: To understand molecular mechanisms underlying ASD and related neurodevelopmental conditions.

Other UTSW researchers who contributed to this study include first author Lauretta El Hayek, M.S., Graduate Student Researcher; Ashlesha Gogate, M.S., Computational Biologist; Ariel Aiken, M.S., Research Assistant; and Kiran Kaur, Ph.D., Senior Research Scientist.

This study was funded by grants from The Welch Foundation (I-1946-20210327), the Walter and Lillian Cantor Foundation, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD099162), and the Peter O’Donnell Jr. Brain Institute Sprouts 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 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. 

DALLAS – Nov. 8, 2023 – Interactions among microorganisms within the human gut may be associated with increased anxiety levels in people with depression, according to research led by UT Southwestern Medical Center.

Using advanced bioinformatics tools like 16S rRNA gene sequencing, researchers analyzed stool samples from 178 patients with a current or past diagnosis of depression who are part of an ongoing Texas Resilience Against Depression (T-RAD) study. The analysis, published in Translational Psychiatry, revealed three networks of gut microbial communities, one of which was correlated with anxiety. While the early findings raise the possibility that gut bacteria could affect anxiety levels, further validation is needed to confirm whether there is a relationship and how that might translate to a clinical setting.

Jane Foster, Ph.D., is Professor of Psychiatry and in the Center for Depression Research and Clinical Care and an Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern.

“This novel approach allowed us to consider the community of bacteria in the gut rather than individual bacteria. One specific microbial community was enriched with butyrate-producing bacteria, and we found that individuals with a low abundance of these key bacteria had higher anxiety,” said Jane Foster, Ph.D., Professor of Psychiatry and in the Center for Depression Research and Clinical Care (CDRC) at UT Southwestern.

A UTSW-led team developed the two longitudinal studies that make up T-RAD, D2K and RAD, in 2020. Spanning 10-plus years and each enrolling 2,500 participants, including from Children’s Health and Parkland Health, the studies aim to comprehensively understand depression onset, recurrence, progression, and treatment response. The work is similar to the hallmark Framingham Heart Study that identified risk factors that now serve as gold-standard metrics for heart disease.

Gut microbiota was one of the first biological markers examined by T-RAD because of its role as a key modulator of human physiology and its strong relationship with mood regulation. Dr. Foster was part of the first research group to connect microbiota to anxiety-like behavior in mice about 15 years ago.

Madhukar Trivedi, M.D., is Professor of Psychiatry, Chief of the Mood Disorders Division, and founding Director of the Center for Depression Research and Clinical Care. Dr. Trivedi is also an Investigator in the Peter O'Donnell Jr. Brain Institute at UTSW.

“Understanding the role of specific microbacteria for the anxiety subtype of depression is exciting. This will extend our research into precise treatment targets using further studies with the gut microbiome to complement our previous findings with brain-based biomarkers,” said Madhukar Trivedi, M.D., Professor of Psychiatry, Chief of the Mood Disorders Division, and founding Director of the CDRC. Drs. Trivedi and Foster are also Investigators in the Peter O’Donnell Jr. Brain Institute at UTSW.

Although most studies have focused on single types of bacteria and their association with illness, the current study seeks clinically relevant affiliations when looking at broader bacterial community structures. This suggests that the study’s approach may provide a more accurate view of bacterial communities that are linked with specific symptoms in patients.

“In this study, we looked at individuals with a current or previous diagnosis of major depressive disorders. But the importance of the microbiome-brain connections extends to healthy individuals as well as the broader fields of psychiatry and neurology,” Dr. Foster said. “The next step will be to validate biomarkers that define individual differences, which could help develop precision approaches to treating depression.”

Other UTSW researchers who contributed to this study are Cherise Chin Fatt, Ph.D., Assistant Professor of Psychiatry; Manish Jha, M.D., Associate Professor of Psychiatry and an O’Donnell Clinical Neuroscience Scholar; Abu Taher Minhajuddin, Ph.D., Professor of Psychiatry in the Peter O’Donnell Jr. School of Public Health; Sangita Sethuram, M.B.A., Performance Improvement Manager at the CDRC; and Taryn L. Mayes, M.S., Program Manager at the CDRC.

Dr. Trivedi holds the Betty Jo Hay Distinguished Chair in Mental Health and the Julie K. Hersh Chair for Depression Research and Clinical Care.

This study was funded by The Hersh Foundation, the Rose Foundation, the Ontario Brain Institute, and the CDRC at UT Southwestern.

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. 02, 2023 – Researchers led by a team at UT Southwestern Medical Center have developed a device that can isolate blood flow to the brain, keeping the organ alive and functioning independent from the rest of the body for several hours.

Juan Pascual, M.D., Ph.D., is a Professor of Neurology, Pediatrics, and Physiology, and in the Eugene McDermott Center for Human Growth and Development at UT Southwestern. He holds the Ed and Sue Rose Distinguished Professorship in Neurology and The Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases.

The device, tested using a pig brain model and described in Scientific Reports, could lead to new ways to study the human brain without influence from other bodily functions. It also could inform the design of machines for cardiopulmonary bypass that better replicate natural blood flow to the brain. The findings build on previous research by study leader Juan Pascual, M.D., Ph.D., and his colleagues.

“This novel method enables research that focuses on the brain independent of the body, allowing us to answer physiological questions in a way that has never been done,” said Dr. Pascual, Professor of Neurology, Pediatrics, and Physiology, and in the Eugene McDermott Center for Human Growth and Development at UT Southwestern. Dr. Pascual is a member of the Peter O’Donnell Jr. Brain Institute at UTSW.

The brain is the body’s master controller for a variety of processes, regulating heart rate, breathing, and sleep and wake cycles, among others. In turn, the brain’s function is affected by factors that originate in the body, such as blood sugar, blood pressure, and oxygenation. Until now, Dr. Pascual explained, there has been no way to separate the brain from the body to study these influences.

In an animal model using anesthesia, the researchers redirected the brain’s blood supply through a pump that maintained or adjusted a range of variables, including blood pressure, volume, temperature, oxygenation, and nutrients. The team found that brain activity and other measurements had minimal to no changes over a five-hour period.

Isolating the brain will allow researchers to manipulate inputs to this organ to study how they change brain function without the body’s influence. For example, Dr. Pascual said, he and his colleagues have already used this system to better understand the effects of hypoglycemia (low blood sugar) in the absence of other factors. Although scientists can induce hypoglycemia by restricting food intake in lab animals or dosing them with insulin, the body can partially compensate for either of these scenarios by altering metabolism and this, in turn, alters the brain. In contrast, the new device allows researchers to alter the glucose content directly in blood pumped to the brain.

Cardiopulmonary bypass devices replicate some functions of the heart and lungs, delivering a continuous flow of oxygenated blood throughout the body. In contrast, the new device delivers blood using a pulsative flow, much like the human heart, a difference that may prevent brain-related side effects sometimes caused by cardiopulmonary bypass machines. Dr. Pascual said this device has been patented to test its effectiveness for this indication.

Dr. Pascual holds the Ed and Sue Rose Distinguished Professorship in Neurology and The Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases.

Other UTSW researchers who contributed to this study include co-first authors Muhammed Shariff, Visiting Junior Researcher in Neurology, Aksharkumar Dobariya, M.S., Graduate Student Researcher in Biomedical Engineering, and Obada Albaghdadi; Jacob Awkal, B.S., Visiting Junior Researcher; Bret Evers, M.D., Ph.D., Assistant Professor of Pathology and Ophthalmology; Ulrike Hoffmann, M.D., Ph.D., Assistant Professor of Anesthesiology and Pain Management and Neurological Surgery; Vikram Jakkamsetti, Ph.D., Instructor of Neurology; Michael Jessen, M.D., Professor and Chair of Cardiovascular and Thoracic Surgery; Bruce Mickey, M.D., Professor Emeritus of Neurological Surgery; Matthias Peltz, M.D., Professor of Cardiovascular and Thoracic Surgery and Surgical Director of Cardiac Transplant; Cameron Longfellow, Perfusionist; Debra Douglass, Chief Perfusionist; Levi Good, Ph.D., Visiting Senior Researcher in Neurology; Gauri Kathote, Data Scientist in Neurology; Gus Angulo, Research Technician in Neurology; Qian Ma, M.D., Ph.D., Senior Research Scientist in Neurology; Ronnie Brown, Senior Research Associate in Neurological Surgery; Misha Dunbar, DVM, Senior Staff Veterinarian; John Shelton, Lab Manager; and Sourav Patnaik, Senior Biomedical Engineering Specialist.

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.

DALLAS – Oct. 31, 2023 – A traditional Chinese medicine whose name means “to open the network of the heart” reduced the risk of heart attacks, deaths, and other major cardiovascular complications for at least a year after a first heart attack, a study led by UT Southwestern Medical Center researchers shows. The findings, published in JAMA, reveal the promise of this compound, one of the first traditional Chinese medicines tested in a large-scale, Western-style clinical trial.

“Many currently used drugs were first recognized by the study of natural or home remedies. While we do not know the exact active ingredient and mechanism of action in this traditional Chinese medicine that caused these benefits, it does point us toward exploring and refining this therapy,” said senior author Eric Peterson, M.D., M.P.H., Professor of Internal Medicine, Vice Provost, and Senior Associate Dean for Clinical Research at UT Southwestern. Dr. Peterson collaborated with Ying Xian, M.D., Ph.D., Associate Professor of Neurology and in the Peter O’Donnell Jr. School of Public Health at UTSW, and colleagues at several Chinese universities and hospitals to perform the study.

Tongxinluo – made of extracts derived from seven herbs and animals including cockroach, scorpion, cicada, centipede, and leech – has long been used as a traditional Chinese therapy to treat patients who have experienced heart attacks and/or strokes. Based on promising results in cellular and animal models, the State Food and Drug Administration of China in 1996 approved its use for angina pectoris and stroke. However, this medicine had never been evaluated in a randomized, double-blind, placebo-controlled clinical trial, a rigorous test required to approve most drug therapies in the U.S. and Europe.

Ying Xian, M.D., Ph.D., Associate Professor of Neurology and in the Peter O'Donnell Jr. School of Public Health at UTSW, collaborated on the study, along with colleagues at several Chinese universities and hospitals.

For the study, the researchers worked with 3,777 patients at 124 clinical centers in China who had suffered the most severe form of heart attack – ST-segment elevation myocardial infarction, in which a blood clot completely blocks a major blood vessel supplying the heart – between May 23, 2019, and Dec. 8, 2020. These patients were treated within hours of onset by surgical or chemical removal of the clot. While they received standard treatments over the next year, such as taking a daily aspirin or medications including beta blockers, half of the patients were randomized to receive tongxinluo as well. The other half took a placebo designed to match the look, smell, and taste of the traditional Chinese medicine.

During the next year, medical providers followed these patients regularly to track the incidence of major adverse cardiac and cerebrovascular events (MACCEs), an umbrella term combining cardiac death, repeat heart attacks, stroke, and emergency procedures to restore blood flow to the heart. Results showed MACCEs were about 30% lower in the group that took tongxinluo compared with those taking the placebo at 30 days. These benefits persisted for one year after discharge. Patients receiving tongxinluo also had a lower risk of individual components of the MACCEs, including a 25% decreased risk of cardiac death. There were no major side effects from tongxinluo, suggesting its use was safe.

Dr. Xian noted that because tongxinluo is made of multiple components, further research should focus on determining which are responsible for these effects and how they reduce the risk of cardiovascular complications in the body. In addition, the benefits from this study will need to be duplicated in other populations in order for the treatment to gain approval from the U.S. Food and Drug Administration. A similar Chinese clinical trial is in the works to test tongxinluo’s safety and efficacy in patients with minor ischemic strokes.

“Many drugs have failed to achieve effects as impressive as this traditional Chinese medicine,” said Dr. Xian, who is an Investigator in the Peter O'Donnell Jr. Brain Institute. “Tongxinluo deserves further study.”

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

The study was funded by the National Key Research and Development Program of China (2017YFC1700503) and a research grant from Shijiazhuang Yiling Pharmacological Co. Ltd.

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.

DALLAS – Oct. 18, 2023 – Everyone experiences stress from time to time. And while brief bouts can be a good thing, prolonged or chronic stress can have negative effects on your overall health.

The causes can be many. This year, money is the most common factor negatively affecting Americans’ mental health, according to a recent survey from Bankrate. Other top factors include health, current events, relationships, and work. Together, these stressors may cause feelings of anxiety, worrisome thoughts, loss of sleep, and depression, the survey showed.

Mary Turner, Ph.D., Associate Professor of Psychiatry and a member of the Peter O'Donnell Jr. Brain Institute at UT Southwestern Medical Center, is a licensed psychologist who specializes in stress reduction and anxiety management and helps individuals going through major life changes and trauma.

To gain perspective on stress and how it affects us, we spoke with Mary Turner, Ph.D., Associate Professor of Psychiatry and a member of the Peter O’Donnell Jr. Brain Institute at UT Southwestern Medical Center. Dr. Turner, a licensed psychologist, specializes in stress reduction and anxiety management and helps individuals going through major life changes and trauma.

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.

DALLAS – Oct. 05, 2023 – The brain circuitry that is disrupted in Alzheimer’s disease appears to influence memory through a type of brain wave known as theta oscillation, a team led by UT Southwestern Medical Center researchers report. The findings, published in Nature Communications, could help researchers design and evaluate new treatments for Alzheimer’s, a condition that affects millions of people around the globe and has no cure.

“We hope to use this data to refine neuromodulation strategies so that they could have a greater ability to treat Alzheimer’s disease and other degenerative brain diseases,” said study leader Bradley Lega, M.D., Associate Professor of Neurological Surgery, Neurology, and Psychiatry and an Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern.

Bradley Lega, M.D., is Associate Professor of Neurological Surgery, Neurology, and Psychiatry and an Investigator in the Peter O'Donnell Jr. Brain Institute at UT Southwestern.

Cholinergic circuits in the brain – networks of cells that communicate with each other using the neurotransmitter acetylcholine – play a critical role in memory. These circuits heavily populate the hippocampus, a region that serves as the brain’s memory headquarters. 

Disruptions in this circuitry are a hallmark of Alzheimer’s disease and related dementias. Cholinesterase inhibitors, one of only two classes of drugs approved to treat the symptoms of Alzheimer’s disease, work by stimulating cholinergic pathways. However, the mechanisms behind how cholinergic circuits support human memory are unknown, Dr. Lega explained.

To help answer this question, he and colleagues at the Texas Computational Memory Lab at UT Southwestern and Columbia University worked with 12 patients at UTSW’s Epilepsy Monitoring Unit who were being evaluated before surgery to remove the damaged parts of their brains that spark seizures. Electrodes implanted in their brains not only help surgeons precisely identify the seizure foci, Dr. Lega said, but they also provide valuable information on the brain’s inner workings.

As the electrodes recorded brain activity, the patients performed memory tasks in which they tried to memorize lists of words and then recall as many as they could. In separate sessions, these volunteers received either a small amount of intravenously delivered scopolamine – a drug typically used for motion sickness that is also known to affect memory by acting on cholinergic circuits – or saline, which has no discernible effect. Between different recall tests in the same session, the volunteers performed math problems as a distraction to clear their minds.

Not surprisingly, scopolamine significantly affected the volunteers’ ability to remember words. Although they could recall about 31% of the word lists on average when given saline, that dropped to about 10% when given scopolamine.

When the researchers analyzed the brain recordings, they saw that scopolamine appeared to disrupt theta oscillations, which are associated with encoding memories. As patients were given this drug, their theta oscillations decreased significantly in intensity. Additional characteristics of these affected oscillations suggested that the hippocampus couldn’t communicate as well internally and with the rest of the brain. These disruptions were most pronounced in the volunteers with the worst recall after scopolamine, supporting the link between cholinergic circuits and theta oscillations.

Together, Dr. Lega said, these findings suggest that one of the principal ways that cholinergic circuits affect memory is through theta oscillations. Thus, improving the quality of theta oscillations could be a focus for developing new Alzheimer’s disease therapies. Theta oscillations could also serve as a biomarker to determine whether experimental therapies are effective in clinical trials.

Other UTSW researchers who contributed to this study include David McDonagh, M.D., Professor of Anesthesiology & Pain Management, Neurological Surgery, and Neurology; Ryan Joseph Tan, B.S., Clinical Data Specialist; and Haley Moore, B.S., Graduate Student Researcher.            

Dr. McDonagh holds The M.T. “Pepper” Jenkins Professorship in Anesthesiology.

This research was funded by grants from the National Institutes of Health (R01-MH104606, R01-NS125250, and R01-NS107357). 

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 has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 19 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 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.

Lenora Volk, Ph.D., Assistant Professor of Neuroscience and Psychiatry and Investigator in the O'Donnell Brain Institute, co-led the study.

Brad Pfeiffer, Ph.D., Assistant Professor of Neuroscience and Investigator in the Peter O'Donnell Jr. Brain Institute at UT Southwestern, is a Southwestern Medical Foundation Scholar in Biomedical Research.

“This research argues that the underlying mechanisms through which memories form in the hippocampus are not as straightforward as the field once thought. It’s not only about strengthening connections,” said Brad Pfeiffer, Ph.D., Assistant Professor of Neuroscience at UT Southwestern and a Southwestern Medical Foundation Scholar in Biomedical Research. Dr. Pfeiffer co-led the study published in Neuron with Lenora Volk, Ph.D., Assistant Professor of Neuroscience and Psychiatry. Drs. Pfeiffer and Volk are Investigators in the Peter O’Donnell Jr. Brain Institute at UTSW.

The hippocampus, a seahorse-shaped part of the cerebrum, has long been recognized as the primary memory-making region of the brain. Decades of research have shown that experiences an animal undergoes cause hippocampal neurons to send electrical signals to each other, altering neuronal connections known as synapses.

An adage in neuroscience is “neurons that fire together, wire together,” implying that memories form when synapses strengthen between groups of activated neurons. However, Dr. Volk said, this concept has been based on studies of brain samples extracted from lab animals a significant time after they engaged in memory-forging experiences, making it challenging to link what was observed in a brain slice and what might actually happen in an intact brain.

To better understand neuronal activity, Drs. Volk and Pfeiffer, along with colleagues at UTSW, took advantage of a new technology called a calcium-modulated photo-activatable ratiometric integrator (CaMPARI). This tool causes neurons to glow green until they are activated during an experience, at which point they permanently switch from green to red, allowing the researchers to identify those neurons that may have participated in memory formation.

UT Southwestern researchers used a recently developed technology that causes neurons to glow green and red to investigate activity during memory formation.

The researchers used CaMPARI on hippocampal excitatory neurons – which have the potential to send electrical signals to each other through synapses – in live rats. They then prompted these rats to explore a linear track, lured by chocolate milk at either end. When the researchers collected samples from the animal brains a short time later, about a third of the altered neurons glowed red, showing they had been activated by this experience.

These activated neurons were distributed nearly equally among two populations, superficial and deep neurons, named for their physical location within the brain. However, when the researchers examined synapses that had formed in these two neuronal populations, they found distinct differences: While connections had strengthened among the activated superficial neurons, those among the activated deep neurons had weakened. The researchers confirmed these findings in living rats by examining data generated by electrodes implanted in their brains.

However, this dichotomy was not as simple as it seemed, Dr. Volk said. When the researchers examined activity in the two groups of neurons in live animals after the memory-making experience, they found that the deep neurons did not only fire less than superficial neurons, but also more precisely. “Thus,” Dr. Volk said, “the deep neurons’ weakened connections may not reflect global synaptic weakening, but rather synaptic refinement among the neurons most important for encoding memory.”

The researchers plan to continue studying this phenomenon both in healthy animals and in models of diseases that affect information processing and memory.

Other UTSW researchers who contributed to this study were co-first authors Marcus Berndt, Ph.D., and Massimo Trusel, Ph.D., Instructor of Neuroscience; and Todd F. Roberts, Ph.D., Associate Professor of Neuroscience and an O’Donnell Brain Institute Investigator. The work was a collaborative effort among three research labs in the O’Donnell Brain Institute: the Pfeiffer Lab, Volk Lab, and Roberts Lab.

This study was funded by grants from the National Institutes of Health (R01MH117149, R01NS104829, and R01NS108424).

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 has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 19 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 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 – Sept. 07, 2023 – Nearly half of Texas youths being treated for depression or suicidal thoughts reported at least one suicide attempt, and 90% had experienced suicidal ideation, according to a study led by UT Southwestern Medical Center researchers. The findings, published in the journal Suicide and Life-Threatening Behavior, represent the data from a registry established in 2020 by the Texas Youth Depression and Suicide Research Network (TX-YDSRN).  

The study offers baseline data on nearly 1,000 volunteer participants collected during the COVID-19 pandemic, when mental health issues spiked among school-age children and teens. All participants provided written informed assent and their parents or guardians provided written informed consent. TX-YDSRN is a research initiative funded by the 86^th Texas Legislature as part of the Texas Child Mental Health Care Consortium (TCMHCC) that was created to improve the evaluation of and response to the increase in youth depression and suicide. UT Southwestern serves as the network’s coordinating hub and source of research oversight and training under the direction of Madhukar Trivedi, M.D.

In addition to UTSW, the study is being conducted at other academic medical centers in Texas including Baylor College of Medicine, Texas A&M, Texas Tech University Health Sciences Center – El Paso, Texas Tech Health Sciences Center – Lubbock, University of North Texas Health Science Center/JPS Health Network, University of Texas at Austin Dell Children's Medical Center, University of Texas Health Science Center at Houston, University of Texas Health Science Center at Tyler, University of Texas Medical Branch, University of Texas Rio Grande Valley, and  University of Texas Health Science Center at San Antonio.

Beth D. Kennard, Psy.D., Professor of Psychiatry and member of UT Southwestern's Peter O'Donnell Jr. Brain Institute and Peter O'Donnell Jr. School of Public Health, is Director of the Suicide Prevention and Resilience program at Children's Health.

“Given that youth depression and suicide are increasing nationally and that Texas ranks very low on access to mental health care, these findings give us an idea of the scope of the challenge. The study will also provide a road map to improve care for depression and suicide in youths across Texas,” said Beth D. Kennard, Psy.D., Professor of Psychiatry and member of UT Southwestern’s Peter O’Donnell Jr. Brain Institute and Peter O’Donnell Jr. School of Public Health.

For the past decade, deaths by suicide, rates of suicide attempts, and suicidal ideation have increased among young people. A 2023 report from the Youth Risk Behavior Survey of ninth-12th graders in the U.S., who responded in 2019 and 2021, found that 14.3% of males and 30% of females reported having seriously considered suicide within the previous 12 months.

The UTSW-led study included data on a diverse population of 8- to 20-year-olds receiving care in a participating clinic who screened positive for depression and/or suicidal ideation or behavior. Researchers found that they had moderate to severe depression and anxiety. Those who had attempted suicide or had suicidal ideation had more severe mental illness, poorer school adjustment and social connectedness, lower resilience, and higher rates of trauma exposure than those without suicidality, data showed.

“The study remarkably showed that close to half of this sample reported at least one prior suicide attempt and many were experiencing significant suicidal intent,” said Dr. Trivedi, who is a Professor of Psychiatry, Chief of the Mood Disorders Division, and founding Director of the Center for Depression Research and Clinical Care (CDRC) at UTSW.

“There is an urgent need for prevention and intervention strategies for suicidal ideation and behavior in youths. These findings highlight important demographic and clinical correlates, which can inform future efforts for more targeted treatments,” added Dr. Kennard, who is also Director of the Suicide Prevention and Resilience program at Children’s Health.

Those who had attempted suicide had higher levels of substance abuse (34.4%) compared with those with ideation (16%) and those with neither attempts nor ideation (10.7%).  

As part of TX-YDSRN, UTSW has connected youths in need of mental health services to clinicians while also providing learning opportunities for practitioners and others in research methods and assessment practices. The longitudinal project will follow participants for two years to identify risk factors, best practices, and contributors to health disparities.

“This project has an incredible opportunity to not only help us better understand the current state of depression and suicidal symptoms in our Texas youths but also to lead us to solutions to improve treatments,” Dr. Trivedi said. “Currently, only about one-third of youths improve with the first depression treatment they receive. Through this project and the engagement of the psychiatry experts at all 12 academic medical centers in Texas, we will find better solutions to reduce depression and suicide in our children.”  

Other UTSW researchers who contributed to this study are Abu Minhajuddin, Ph.D., Professor in the O’Donnell School of Public Health; Holli Slater, Ph.D., Clinical Research Manager at CDRC; and Taryn L. Mayes, M.S., Program Manager at CDRC.

Dr. Trivedi holds the Betty Jo Hay Distinguished Chair in Mental Health and the Julie K. Hersh Chair for Depression Research and Clinical Care.

This study was funded by the Texas Youth Depression and Suicide Research Network (TX-YDSRN), a research initiative of the Texas Child Mental Health Care Consortium (TCMHCC). The TCMHCC was created by the 86th Texas Legislature and, in part, funds multi-institutional research to improve mental health care for children and adolescents in Texas. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations. The TX-YDSRN is implemented under the leadership of the central UT Southwestern HUB (Madhukar Trivedi, M.D., Principal Investigator; Sarah Wakefield, M.D., Medical Director (Texas Tech University Health Science Center Lubbock), Abu Minhajuddin, PhD, Data/Statistics Lead, and Holli Slater, PhD, Operations Lead).

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 has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 19 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 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 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.

DALLAS – Aug. 29, 2023 – Patients whose brains appear older on scans than their chronological age showed less improvement on sertraline, a first-line drug treatment for major depressive disorder (MDD), researchers from UT Southwestern Medical Center reported. The findings, published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, could eventually lead to new ways to predict the effectiveness of medications for patients with MDD, which affects hundreds of millions worldwide.

Study leader Manish Jha, M.D., Assistant Professor of Psychiatry, is a member of the Peter O'Donnell Jr. Brain Institute at UT Southwestern and an O'Donnell Clinical Neuroscience Scholar.

“This report is the first to show that brain age can be a reliable and potentially clinically useful biomarker to predict antidepressant treatment outcomes,” said study leader Manish Jha, M.D., Assistant Professor of Psychiatry, a member of the Peter O’Donnell Jr. Brain Institute at UT Southwestern, and an O’Donnell Clinical Neuroscience Scholar.

Recent studies suggest patients with MDD show evidence of accelerated brain aging – a condition in which their brains appear significantly older on magnetic resonance imaging (MRI) scans than their ages, Dr. Jha explained. This brain aging phenomenon, which eventually may be used to diagnose and treat MDD, also has been associated with more severe depression symptoms. However, whether accelerated brain aging is connected with antidepressant efficacy was unknown.

To answer this question, Dr. Jha and his colleagues, including Madhukar Trivedi, M.D., Professor of Psychiatry and Director of the Center for Depression Research and Clinical Care at UTSW, used data from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study. This national multicenter study led by Dr. Trivedi seeks to identify clinical and biological markers that can predict treatment response for depression.

As part of the study, which includes patients from UT Southwestern and four other U.S. sites, 290 participants with MDD and 39 healthy volunteers received two brain scans one week apart. Roughly half of the MDD patients were prescribed sertraline (also known by the brand name Zoloft) for eight weeks, and the other half took an identical-looking placebo.

Using an artificial intelligence algorithm developed for previous brain aging studies, the researchers analyzed the scans to determine participants’ brain age and compared it to their chronological age. Brain age appeared stable from the first to second scans, suggesting it was a reliable measurement that didn’t differ substantially within short periods – an important factor for brain age to eventually be used as a clinical biomarker.

The researchers found that patients with MDD had brains that appeared about three years older than their age, compared to less than a year for the healthy volunteers, mirroring the results of previous studies. In addition, the older their brain age compared to their chronological age, the smaller the improvement in depression symptoms for those on sertraline, including impulsivity, pessimism, helplessness, perceived lack of social support, and despair. There was no significant effect in patients taking the placebo.

Dr. Jha noted that if future studies confirm these results, brain age eventually could be used to determine which medications might be most effective for patients with depression – providing a precision-medicine approach for treating this condition. Future research also will focus on whether brain age can predict the efficacy of other treatments for MDD, such as repetitive transcranial stimulation.

Dr. Trivedi holds the Betty Jo Hay Distinguished Chair in Mental Health and the Julie K. Hersh Chair for Depression Research and Clinical Care.

Other UTSW researchers who contributed to this study were Cherise Chin Fatt, Ph.D., Assistant Professor of Psychiatry; Abu Taher Minhajuddin, Ph.D., Professor of Psychiatry and in the Peter O’Donnell Jr. School of Public Health; and Taryn L. Mayes, Program Manager for the Center for Depression Research and Clinical Care.

The EMBARC study (NCT01407094) was supported by the National Institute of Mental Health (U01MH092221 and U01MH092250) and The Hersh Foundation.

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 has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 19 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 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 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.

DALLAS – Aug. 16, 2023 – Overdose deaths from opioids, including prescription painkillers and synthetics like fentanyl, continue to rise. According to the Centers for Disease Control and Prevention, an estimated 187 people in the U.S. die every day of opioid overdoses, most involving illicit and dangerous versions of fentanyl.

According to a survey conducted by health policy research group KFF in July and released in August, about 3 in 10 adults say they or a family member have been addicted to opioids.

Stacey Hail, M.D., FACMT, Associate Professor of Emergency Medicine, has a forensic toxicology practice and reviews opioid cases for the U.S. Department of Justice.

Enas Kandil, M.D., Associate Professor of Anesthesiology and Pain Management, leads quality improvement projects on opioid safety initiatives at UTSW and Parkland Health.

To provide perspective on the evolving epidemic, we spoke with four experts at UT Southwestern Medical Center about the dangers of opioid addiction, how to recognize an overdose, and treatment options including Narcan, which was recently approved by the Food and Drug Administration to be sold over the counter.

Stacey Hail, M.D., FACMT, Associate Professor of Emergency Medicine in UTSW’s Division of Medical Toxicology, treats patients in the Emergency Department at Parkland Memorial Hospital and consults on toxicology patients through the North Texas Poison Center. Dr. Hail has a forensic toxicology practice and reviews opioid cases for the U.S. Department of Justice as well as for attorneys in civil matters.

Enas Kandil, M.D., Associate Professor of Anesthesiology and Pain Management, leads quality improvement projects on opioid safety initiatives at UTSW and Parkland Health, with the goal of regulating opioid-prescribing practices and ensuring hospital compliance, thus improving patient safety.

Sidarth Wakhlu, M.D., Professor of Psychiatry and a member of the Peter O'Donnell Jr. Brain Institute, is Director of the Addiction Psychiatry Fellowship Program at UTSW and Associate Director of the Addiction Division.

Kurt Kleinschmidt, M.D., Professor of Emergency Medicine, leads an Addiction Medicine team at UTSW and is Medical Director of the Perinatal Intervention Program (PIP) and Service Chief of the Integrated Family Planning Opioid Program at Parkland Health.

Sidarth Wakhlu, M.D., Professor of Psychiatry and a member of the Peter O’Donnell Jr. Brain Institute, specializes in the treatment of substance abuse disorders. He is Director of the Addiction Psychiatry Fellowship Program and Associate Director of the Addiction Division in Psychiatry.

Kurt Kleinschmidt, M.D., Professor of Emergency Medicine in the Division of Medical Toxicology, leads an Addiction Medicine team at UT Southwestern. He also is Medical Director of the Perinatal Intervention Program (PIP) at Parkland Health, which cares for pregnant women with substance abuse disorders, and Service Chief of the Integrated Family Planning Opioid Program at Parkland.

DALLAS – Aug. 14, 2023 – Myron Frederick Weiner, M.D., Professor Emeritus of Psychiatry at UT Southwestern Medical Center and a noted clinical researcher in geriatric psychiatry and Alzheimer’s disease, died July 17 in Dallas. He was 89.

A faculty member at UT Southwestern for more than 50 years, Dr. Weiner served as Vice Chair of Psychiatry, directed the Clinical Core of UTSW’s federally funded Alzheimer’s Disease Center, and established the Geriatric Psychiatry training program at the Medical Center. Following his retirement in 2013, Dr. Weiner continued guiding and helping junior faculty and trainees as a Professor Emeritus.

“Dr. Weiner was a true mentor, teacher, and collaborator. He had a gift for finding the natural talents of each team member and developing them further,” said Carol Tamminga, M.D., Professor and Chair of Psychiatry who holds the Stanton Sharp Distinguished Chair in Psychiatry. “He cared about the success of others more than himself. We will miss his wisdom and perspective as well as his presence.”

Dr. Weiner received his medical degree from the Tulane University School of Medicine in 1957 and completed his internship and residency at Parkland Memorial Hospital. A U.S. Air Force veteran, Dr. Weiner found his career calling in seeking to manage the emotional and behavioral symptoms of dementing illness following a 1984-1985 fellowship in geriatrics and adult development at the Icahn School of Medicine at Mount Sinai in New York.

Dr. Weiner was a prolific medical writer with more than 200 scientific publications as well as authorship or co-authorship of more than 10 books. He also served as an editor of The American Psychiatric Publishing Textbook of Alzheimer Disease and Other Dementias (2009).

In 2014, the Presbyterian Village North Foundation (PVN) donated $1 million to the Southwest Medical Foundation to support Alzheimer’s research at UT Southwestern, in recognition of the work of Dr. Weiner and Paul Chafetz, Ph.D., who helped establish the Alzheimer’s Disease Care Wing at PVN. The gift was used to establish the Presbyterian Village North Foundation Distinguished Chair in Alzheimer’s Disease Therapeutic Research, currently held by Joachim Herz, M.D., Professor of Molecular Genetics, Neuroscience, and Neurology in UT Southwestern’s Peter O’Donnell Jr. Brain Institute.

Dr. Weiner held the Aradine S. Ard Chair in Brain Science and the Dorothy L. and John P. Harbin Chair in Alzheimer’s Disease Research while a UTSW faculty member. His awards and recognitions included the Castle Connolly Medical Ltd. America’s Top Doctors (2008), the American Psychiatric Association Distinguished Life Fellow (2003), and the Texas Society of Psychiatric Physicians Psychiatric Excellence Award (1997).

He is survived by sons Daniel (Karen) and Gary Weiner (Mary Anne), stepson Darrel Harmon (Lora), stepdaughter Holly Pennett (Barry), seven grandchildren and their spouses, and one great-grandson.

Contributions can be made to Alzheimer’s care and research at UT Southwestern, 5323 Harry Hines Blvd., Dallas, Texas 75390, c/o Office of Development.

Dr. Herz also holds the Thomas O. and Cinda Hicks Family Distinguished Chair in Alzheimer’s Disease 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 has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 19 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 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 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.

DALLAS – Aug. 10, 2023 – Researchers led by a team at UT Southwestern Medical Center have identified cellular and molecular features of the brain that set modern humans apart from their closest primate relatives and ancient human ancestors. The findings, published in Nature, offer new insights into human brain evolution.

Genevieve Konopka, Ph.D., Professor of Neuroscience, is a Jon Heighten Scholar in Autism Research and holds the Townsend Distinguished Chair in Research on Autism Spectrum Disorders.

“Most evolutionary studies on the human brain have focused on neurons because this cell type was thought to be responsible for our intelligence and enhanced cognitive abilities. This study gives us a renewed appreciation for other cells involved in brain function and the role they have played both in advancing cognition and our susceptibility to a number of cognitive diseases,” said study leader Genevieve Konopka, Ph.D., Professor of Neuroscience and a member of the Peter O’Donnell Jr. Brain Institute at UT Southwestern.

Since ancient times, people have been curious about what gives humans abilities that other animals don’t have, such as speech and language, Dr. Konopka explained. A range of previous studies have sought to answer this question by examining brain anatomy or performing genetic or molecular studies on whole brains or sections, experiments that provide a view of thousands of cells at a time.

Dr. Konopka and her colleagues theorized more could be gleaned from looking at brain characteristics at the cellular level, a feat only possible due to recent advances in technology. In this study, researchers in the Konopka lab, including lead author and O’Donnell Brain Institute Neural Scientist Training Program Fellow Emre Caglayan, B.S., together with colleagues at The George Washington University, Emory University, and the University of California, Santa Barbara, focused on Brodmann area 23 (BA23) in the posterior cingulate cortex. BA23 is also part of the default mode network – an interconnected complex of regions that remain active when the brain is in a state of wakeful rest – and has been implicated in schizophrenia.

Rather than look at BA23 as a whole, the researchers used a relatively new technique called single nuclei RNA-sequencing to investigate what types of cells compose this area, comparing samples from humans, chimpanzees, and rhesus monkeys. They found that, in contrast to the nonhuman primates, humans have a far larger proportion of oligodendrocyte progenitor cells (OPCs), precursors to a type of cell known to provide support and insulation for neurons, and increasingly implicated in modulating brain circuitry. In addition, two subtypes of excitatory neurons – which share information through electrical impulses – showed increased expression in humans in the gene that makes FOXP2, a protein involved in brain development related to speech and language.

In another experiment, the researchers compared the DNA of modern humans with that of Neanderthals and Denisovans, ancient human relatives. They looked not only at differences in their genetic codes, but also whether these differences occurred in areas of the genome where cellular machinery regulates gene expression. Their search identified dozens of genes that functionally differ between humans and their ancient relatives, particularly in excitatory neurons in the upper layers of BA23, which could offer additional insight into human brain evolution in future studies.

Together, Dr. Konopka said, these findings offer a road map for understanding how human brains developed their unique abilities that set people apart from other species.

Dr. Konopka is a Jon Heighten Scholar in Autism Research and holds the Townsend Distinguished Chair in Research on Autism Spectrum Disorders.

Other UTSW researchers who contributed to this study include postdoctoral researcher Yuxiang Liu, Ph.D., and graduate students Rachael Vollmer, B.S., and Emily Oh, B.S.

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 has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 19 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 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 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.