Scientific Discoveries
UT Southwestern Medical Center is home to many nationally and internationally recognized physicians and scientists, including six Nobel Laureates, 25 members of the National Academy of Sciences, and 24 members of the National Academy of Medicine (formerly the Institute of Medicine). Their investigations range from the microscopic level to the whole patient and have resulted in several notable discoveries.
Aging/Alzheimer’s
- Steven McKnight, Ph.D., and Andrew Pieper, Ph.D., identified a compound (P7C3) and demonstrated that it preserves newly created brain cells and boosts learning and memory. The study, funded by a National Institutes of Health Director’s Pioneer Award, has led to further investigations into the mechanism by which P7C3 protects cells from dying and whether the compound might have any protective effect for various neurodegenerative diseases.
- Scientists led by Roger Rosenberg, M.D., have created an experimental vaccine against beta-amyloid, the small protein that forms plaques in the brain and is believed to contribute to the development of Alzheimer’s disease. Compared with previous so-called DNA vaccines, the new experimental vaccine stimulated more than 10 times as many antibodies that bind to and eliminate beta-amyloid.
Cancer
- John Minna, M.D., and Adi Gazdar, M.D., have spent the past 30 years elucidating the genetic changes associated with the development of lung cancer. Their work seeks to discover these changes and use them as biomarkers – molecular signatures of disease – both to detect lung cancer earlier and to develop new therapies. Their approach is advancing personalized medicine, which aims to target the unique characteristics of an individual’s tumor with the best current therapies.
- Jonathan Uhr, M.D., investigates the enigmas of breast cancer. About 10 years ago, he developed a technique to detect cancer cells that are shed from a primary tumor and go on to circulate in the blood. The test has been commercialized and now is used routinely in laboratories to selectively pluck circulating cancer cells out of the bloodstream for further analysis and characterization.
- Pioneering discoveries by Steve McKnight, Ph.D., David Russell, Ph.D., Rick Bruick, Ph.D., and Kevin Gardner, Ph.D. led to the discovery of an important cancer driver, HIF-2a, and the finding of a vulnerability in the protein’s structure. Small molecules were identified that exploited this vulnerability and neutralized HIF-2a. A biotech company was founded, Peloton Therapeutics, which developed the initial small molecule inhibitors into a drug. Research by James Brugarolas, M.D, Ph.D. provided the first evidence that targeting HIF-2a was an effective strategy against kidney cancer. Furthermore, HIF-2a inhibitors were more effective and better tolerated than the standard kidney cancer drug, sunitinib. UT Southwestern received a Specialized Program of Research Excellence (SPORE), one of two such awards for kidney cancer in the country.
Cancer/Stem Cells
- A team led by Sean Morrison, Ph.D., at the Children’s Medical Center Research Institute at UT Southwestern has identified the environment in which blood-forming stem cells survive and thrive within the body, an important step toward increasing the safety and effectiveness of bone-marrow transplantation. Another study, led by Luis Parada, Ph.D., of a common and deadly kind of brain tumor revealed a subset of cancer stem-like cells that appear not only to survive standard chemotherapy but also probably serve as the source for cancer recurrence.
Cardiology
- Helen Hobbs, M.D., and Jonathan Cohen, Ph.D., are among the world’s leading experts on the genetic factors associated with heart disease. They have shown that humans with mutations in PCSK9 had a 28 percent reduction in LDL cholesterol levels and an 88 percent reduction in risk of coronary heart disease over a 15-year period, compared to those without the mutation. An editorial in The New England Journal of Medicine credited their work with “spurring interest in PCSK9 therapeutics,” which now are under development by several pharmaceutical companies.
- The work of Eric Olson, Ph.D., is regarded as a major step in finding genetic targets for treatment of congenital heart defects and adult heart disease, and it has illuminated the fundamental principles of organ formation. He and his team have discovered networks of genes that orchestrate the formation of the heart and have shown how inherited genetic mutations in these genes cause congenital heart disease, the most frequent form of birth defect.
- Researchers including Dr. Olson and Hesham Sadek, M.D., Ph.D., have pinpointed a molecular mechanism needed to unleash the heart’s ability to regenerate. Researchers found that microRNAs – tiny strands that regulate gene expression – contribute to the heart’s ability to regenerate up to one week after birth. Soon thereafter the heart loses the ability to regenerate. Identifying the heart’s natural regenerative on-off switch is a critical step toward developing eventual therapies for damage suffered following a heart attack.
- UT Southwestern-based research indicates that lowering “bad” blood cholesterol earlier in life, even by a modest amount, confers substantial protection from coronary heart disease. The 2006 findings were based on 15 years of data tracking more than 12,000 multi-ethnic subjects, and were reported in The New England Journal of Medicine.
- The Dallas Heart Study, a groundbreaking investigation of cardiovascular disease involving thousands of Dallas County residents, was launched in 1999. Nearly 6,000 people participated in the study, in which researchers used molecular and clinical research techniques to examine a large multi-ethnic group of individuals to develop new biotechnology and to establish a novel training program for scientist physicians.
Cholesterol
- UT Southwestern researchers have identified nearly 30 disease-causing genes, including in 1983 the gene responsible for familial hypercholesterolemia, an inherited condition that causes extremely high levels of cholesterol and heart attacks at an early age. That discovery by Michael Brown, M.D., and Joseph Goldstein, M.D., contributed to the pair winning the Nobel Prize in physiology or medicine for their research uncovering the underlying mechanisms of cholesterol metabolism.
- Researchers led by Jay Horton, M.D., have shown that a protein responsible for regulating “bad” cholesterol in the blood works almost exclusively outside cells, providing clues for the development of therapies to block the protein’s disruptive actions.
Depression
- UT Southwestern researchers led the six-year STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study, which began in 2001 and was the largest study on treatments for depression. STAR*D was the first benchmark investigation to implement specific step-by-step medication treatment guidelines based on patients’ symptoms and medication side effects.
- As a follow-up to STAR*D, Madhukar Trivedi, M.D., now is leading a national clinical trial to find biomarkers that can better predict how people suffering from depression will respond to specific medications. These biomarkers will aid physicians in personalizing treatments for their patients. The previous study, also led by Dr. Trivedi, revealed that as many as one in every three depressed patients must try multiple antidepressants before finding one that works.
Diabetes
- UT Southwestern researchers led by Roger Unger, M.D., showed in mice that insulin becomes completely superfluous and its absence does not cause diabetes or any other abnormality when the actions of glucagon are suppressed. These new findings may lead to an alternative to insulin as a treatment for type 1 diabetes, which affects about 1 million people in the U.S.
- Dr. Unger also has pioneered research into the actions of the hormone leptin against diabetes. He and his team, using mouse models, found that leptin administered instead of insulin showed better management of blood-sugar variability and lipogenesis, the conversion of simple sugars into fatty acids.
Digestive and Liver Diseases
- Helen Hobbs, M.D., and Jonathan Cohen, Ph.D., have identified in mice that chronic overexpression of PNPLA3 leads to a fatty liver. In people, nonalcoholic fatty liver disease is a burgeoning health problem that affects one-third of adults and an increasing number of children in developed countries. The disease begins with the aberrant accumulation of triglyceride in the liver, which in some people elicits an inflammatory response that can progress to cirrhosis and liver cancer.
Innate Immunity
- The exploration of the interface between man and microbe is one of the most important frontiers in science. In 2011, leaders at UT Southwestern established the Center for the Genetics of Host Defense under the direction of Nobel Laureate Bruce Beutler, M.D., to accelerate the discoveries of basic research and its applicability to patients. The fifth UTSW faculty member to win the Nobel Prize, Dr. Beutler was honored for the discovery of receptor proteins that recognize disease-causing agents and activate innate immunity, the first step in the body´s immune response.
- Scientists led by Zhijian “James” Chen, Ph.D., are exploring the mechanisms of signal transduction, namely how a cell communicates with its surroundings and within itself. They are focused on investigating how a cell detects harmful or foreign threats and mounts an appropriate response to restore homeostasis. Cell signaling and host defense research from Dr. Chen’s lab has revealed unexpected cellular functions that contribute to normal and cancerous cell growth and to immune response.
Metabolism and Nutrition
- In a landmark study published in 2002 in The New England Journal of Medicine, a team of researchers led by Abhimanyu Garg, M.D., reported that leptin replacement therapy not only controlled severe insulin resistance and lowered triglyceride levels in patients with severe lipodystrophy but also decreased fat accumulation in the liver, an abnormality for which there has been no effective therapy.
- Research in the Center for Human Nutrition is significant for everyone. Center investigators, led by Scott Grundy, M.D., Ph.D., were the first to prove the “Mediterranean diet” healthy, discover that antioxidants help prevent atherosclerosis, and define the varieties of fatty foods that are harmful.
Obesity
- The prevalence of weight-related issues among people dealing with chronic stress and depression may be caused by ghrelin, the so-called “hunger hormone” found in the gastrointestinal tract. Research by Jeffrey Zigman, M.D., Ph.D., has found that ghrelin is involved in sending hunger signals to the brain, and that chronic stress and depression causes an elevation in its levels. These stress-induced ghrelin rises in mice lead to overeating and increased body weight, a finding that Dr. Zigman says is likely to be applicable to humans.
Osteoporosis/Kidney Stones
- Charles Y.C. Pak, M.D., and his research team have played a critical role in the development of several drugs used worldwide – including Citracal for the prevention of osteoporosis and Urocit-K for the control of kidney stones – as well as widely recognized diagnostic methods for measuring the risk factors for kidney stones.
Preventive Medicine
- Jarett Berry, M.D., has shown that people’s early-life decisions can have a significant impact on the rest of their lives. The risk factors we develop in younger and middle ages are going to continue to determine our heart disease risk across our lifetime. Being physically fit during your 30s, 40s, and 50s not only helps extend lifespan, but it also increases the chances of aging healthily, free from chronic illness, investigators led by Dr. Berry have found.
- A protein in the blood considered to be a key indicator of future heart disease may vary considerably among women and men, as well as blacks and whites, according to researchers led by Amit Khera, M.D. C-reactive protein, or CRP, is released as part of the human body's inflammation response. Abnormal fatty deposits on the interior walls of rupture-prone arteries may also cause higher levels of CRP, which is why the protein has been touted recently as a means to determine the relative risk of heart disease in some patients.
- James de Lemos, M.D., and other UT Southwestern clinicians have discovered that a more sensitive version of a blood test typically used to confirm that someone is having a heart attack could indicate whether a seemingly healthy, middle-aged person has unrecognized heart disease. Using this highly sensitive test for a protein called cardiac troponin T (cTnT) could detect the protein in about 25 percent of supplied blood samples. The study also found that people with detectable levels of troponin T were nearly seven times more likely to die within six years from heart disease than healthy individuals.
Transplants
- Peter Stastny, M.D., is pushing past conventional testing with new methods that may allow doctors to predict whether an organ recipient will develop antibodies rejecting the transplant. Collaborating with colleagues in Germany, Dr. Stastny for the first time identified antibodies associated with transplant rejection of otherwise healthy kidneys. The research appeared in The New England Journal of Medicine.
Trauma
- Hunt Batjer, M.D. – a UT Southwestern alumnus, former trainee, and faculty member – returned to campus as Chairman of Neurological Surgery. A renowned neurosurgeon with expertise in cerebrovascular diseases, Dr. Batjer is changing how amateur and professional sports teams evaluate and treat head injuries as he co-chairs the National Football League’s Head, Neck and Spine Medical Committee.