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Jay H. Chung, M.D., Ph.D.

Senior Investigator

10 Center Dr
Bethesda, MD 20814
United States

301-496-3075
301-480-4557

Biography

Dr. Jay H. Chung earned a B.S. in electrical engineering and computer science and a B.S. in biology from M.I.T. before receiving an M.D. and Ph.D. in genetics from Harvard Medical School, where he was awarded the James Tolbert Shipley Prize for Excellence in Research. After an internship and residency in internal medicine at the Brigham and Women’s Hospital, he became an endocrinology fellow at the National Institute of Diabetes and Digestive and Kidney Diseases at the NIH, where he worked with Gary Felsenfeld. He is currently a tenured senior investigator in the Laboratory of Obesity and Aging Research in NHLBI. Dr. Chung has received numerous awards for his research, including the NHLBI Directors Awards and Orloff Awards.

Research

Research Interests

Dr. Chung's primary research interest is in understanding the relationship between mitochondria and diseases associated with obesity and aging.  The mechanisms by which mitochondria and the rest of the cell communicate with and influence each other has been the primary focus of Dr. Chung’s research.

As an endocrinologist, Dr. Chung has been interested in the “obesity-aging” paradox: an average American gains approximately 30 lbs over 30 years in midlife, even though food intake decreases during this period.  The weight gain, which occurs primarily in the abdominal/visceral depot, is an important driver of many chronic diseases of Western society: type 2 diabetes, cardiovascular diseases and even cancer and Alzheimer’s disease. One possible explanation for the paradox is that aging leads to loss of mitochondria, the organelle that burns fat and generates energy. In a recent Cell Metabolism paper, Dr. Chung’s group revealed the mechanism for the mitochondrial loss: increased activity of DNA-dependent protein kinase (DNA-PK) during aging suppresses the activity of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism and mitochondrial function. 

Dr. Chung’s group is also working to understand the key molecular mechanisms that underlie the beneficial effects of caloric restriction in order to develop therapeutic strategies that mimic these effects and protect against metabolic diseases. Resveratrol, perhaps best known as a component of red wine, has been shown to mimic certain beneficial aspects of caloric restriction, including mitochondrial biogenesis, autophagy and protection against obesity-related diseases such as type 2 diabetes. Dr. Chung and his colleagues are studying the signaling pathways activated by resveratrol to tease apart their modes of action and discover the pathways that contribute to the prevention of type 2 diabetes. Using various animal models, they have demonstrated that while resveratrol does not directly target SIRT1, as previously proposed, it does inhibit phosphodiesterases (PDEs), which results in increased levels of the signaling molecule cyclic AMP and activation of AMPK. They have been able to mimic the protective effects of resveratrol with a selective inhibitor of PDE4. This work was selected as a "best of 2012 paper" by Cell.

Dr. Chung believes that many common obesity and aging-related diseases are linked to mitochondrial production of oxygen radicals, which activate the inflammatory pathways. Indeed, signature hallmarks of obesity and aging are mitochondrial dysfunction and inflammation. His laboratory is employing an extensive range of in vitro and mouse models to understand the biochemical pathways that couple mitochondrial dysfunction to vascular diseases, immune dysfunction (inflammation), type 2 diabetes, fatty liver and neurodegeneration.

Awards
Orloff Award
NHLBI

Publications