Jay Chung earned a B.S. in electrical engineering and a B.S. in biology from the Massachusetts Institute of Technology before receiving a M.D. and Ph.D. in genetics from Harvard Medical School, during which he received the James Tolbert Shipley Prize for Research in 1998. After an internship and residency in internal medicine at Brigham and Women’s Hospital, he became an endocrine fellow at the National Institute of Diabetes and Digestive and Kidney Diseases at the NIH where he worked with Gary Felsenfeld. He moved to the NHLBI in 1994 as an Investigator in the Laboratory of Biochemical Genetics.
Dr. Chung's primary research interest is in understanding how aging decreases our ability to burn calories and generate energy. This aging-related metabolic decline plays an important role in the development of obesity and obesity-related diseases such as type 2 diabetes and cardiovascular disease. Dr. Chung is 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.
Dr. Chung’s laboratory is focused on three key enzyme pathways—DNA-dependent protein kinase (DNA-PK), SIRT1 and AMP-dependent kinase (AMPK)—that are linked with oxidative stress, aging, inflammation, metabolic diseases as well as with the effects of caloric restriction. He and his colleagues use transgenic approaches in cells and mice to manipulate these pathways and to monitor the metabolic outcomes. For example, caloric restriction results in a shift from the utilization of carbohydrates to stored fats as the primary energy source. By examining mitochondrial levels and gene expression patterns in cells and tissues, it is possible to observe the shift towards fat burning that arises from different genetic perturbations.
Resveratrol, perhaps best known as a component of red wine, has been shown to mimic certain beneficial aspects of caloric restriction, including protection against type 2 diabetes. It is also a "dirty" compound in the sense that it activates several molecular pathways, some of which may be beneficial, others of which may prove toxic over the long term. 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 cAMP 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.
Recently, the FDA approved a drug that inhibits PDE4 for the treatment of chronic obstructive pulmonary disease (COPD). An incidental finding from the clinical trial was that COPD patients who happened to be diabetic had significantly lower blood glucose levels if they were on this inhibitor, thus confirming the effect Dr. Chung observed in animals. This has led Dr. Chung to initiate a clinical trial in subjects with pre-diabetes to investigate the glucose-lowering mechanism of PDE4 inhibition in humans.
Dr. Chung believes that many aging-related diseases that are not normally considered metabolic diseases are nonetheless related. For example, obesity and type 2 diabetes are significant risk factors for the development of Alzheimer’s disease in the elderly. His laboratory is bringing similar strategies to bear on the biochemical pathways that couple obesity, type 2 diabetes, and Alzheimer’s disease.