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

Dr. Chung’s laboratory seeks to understand how metabolic dysfunction drives aging and chronic disease, with a particular focus on mitochondrial dysfunction and the inflammatory pathways it activates. This work is based on the premise that seemingly distinct diseases—including neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, cardiovascular disease, fatty liver disease, and cancer—share fundamental mechanisms rooted in metabolic and mitochondrial dysfunction. Increasing evidence also implicates mitochondrial dysfunction in diseases not traditionally viewed as metabolic, including autism and infection-associated chronic diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. A common feature of these diverse conditions is chronic, low-grade inflammation, or metabolic inflammation, which can be initiated and sustained by dysfunctional mitochondria.

A major focus of the laboratory is defining how damaged mitochondria trigger inflammatory signaling. One important mediator is mitochondrial DNA (mtDNA), which can be released from mitochondria into the cytosol and extracellular space, where it activates innate immune pathways, including the type I interferon response, and promotes inflammation. Dr. Chung’s laboratory discovered that oxidation of the voltage-dependent anion channel (VDAC) disrupts mitochondrial membrane integrity, leading to permeabilization of both the outer and inner mitochondrial membranes and subsequent release of mtDNA. This work identified VDAC oxidation as a previously unrecognized mechanism linking mitochondrial dysfunction to inflammation.

Building on this discovery, the laboratory developed a novel class of small-molecule therapeutics, Inhibitors of VDAC Oxidation (IVOs). By selectively targeting oxidized VDAC, IVOs are designed to preserve mitochondrial integrity, prevent mtDNA release, and suppress the downstream inflammatory response. The laboratory is currently evaluating IVOs as potential therapies for a broad range of aging- and metabolism-associated diseases.

Toward a Unified Therapeutic Strategy-Chronic diseases account for the majority of healthcare expenditures in the United States and represent an increasingly urgent global challenge as life expectancy continues to rise. Despite sharing common biological mechanisms, these diseases are generally treated as independent conditions, requiring separate therapeutic strategies. As an endocrinologist, Dr. Chung has long been interested in a fundamentally different approach: developing a single therapeutic strategy that targets a common upstream driver of multiple chronic diseases rather than treating each disease individually. The laboratory’s goal is to protect mitochondrial function and prevent metabolic inflammation at its source.

The discovery of VDAC oxidation as a mechanistic link between mitochondrial dysfunction and inflammation, together with the development of IVOs, provides a potential path toward this goal. The laboratory is testing whether targeting mitochondrial dysfunction can simultaneously prevent or treat multiple diseases of aging and metabolism, with the long-term vision of developing IVOs into a new class of broad-spectrum therapeutics for chronic disease.

Dr. Jay H. Chung earned bachelor’s degrees in Electrical Engineering and Computer Science and in Biology from the Massachusetts Institute of Technology (M.I.T.). He subsequently received his M.D. and Ph.D. in Genetics from Harvard Medical School, where he was awarded the James Tolbert Shipley Prize for Excellence in Research.

Following an internship and residency in Internal Medicine at Brigham and Women’s Hospital, Dr. Chung completed a fellowship in Endocrinology at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health (NIH), where he conducted research under the mentorship of late Gary Felsenfeld.

Dr. Chung is currently a tenured Senior Investigator and Chief of the Laboratory of Obesity and Aging Research at the National Heart, Lung, and Blood Institute (NHLBI), NIH. His research has been recognized with numerous honors, including multiple NHLBI Director’s Awards and Orloff Scientific Awards.