Paul Hwang, M.D., Ph.D.

Cardiovascular and Cancer Genetics

Dr. Hwang’s lab is focused on investigating the intricate roles of mitochondrial regulation and cellular metabolism on human health and disease. Their earlier research revealed that p53, a critical tumor suppressor gene known as the "guardian of the genome," plays a significant role in promoting mitochondrial function (Matoba S et al, Science 2006), enhancing aerobic exercise capacity and preventing chemotherapy-induced heart failure. They also found that inhibiting mitochondrial metabolism, which is induced by gain-of-function mutations of p53 found in Li-Fraumeni syndrome (LFS), can prevent tumorigenesis. In addition to their continued exploration of p53’s role in maintaining cardiac mitochondrial homeostasis, they have identified WASF3 as a potential mediator of mitochondrial dysfunction and bioenergetic deficiencies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a poorly understood, debilitating disorder with no effective treatment. This finding opens new avenues for studying the molecular underpinnings of ME/CFS, potentially leading to targeted treatments. Furthermore, Dr. Hwang’s lab has found a specific mitochondrial signaling pathway that regulates skeletal muscle adaptation to exercise, a mechanism that increases fatty acid oxidation and prevents obesity, illustrating the impact of mitochondrial function on metabolic health. These mechanistic insights, which are currently being explored through human translational studies, may permit the development of new strategies for decreasing the profound disabilities associated with ME/CFS as well as improving cardiovascular health.

Dr. Paul Hwang earned BA degrees in biochemistry and chemistry from the University of Kansas in 1985, after which he spent a year at the Swiss Federal Institute of Technology and University of Zurich as a Fulbright Scholar. He graduated from the Johns Hopkins University School of Medicine with an MD and PhD in 1993. He did his internship and residency in internal medicine at the UCSF School of Medicine in San Francisco, followed by a clinical fellowship in cardiology and postdoctoral research in molecular oncology at the Johns Hopkins University School of Medicine.

Upon completion of his training in 2001, Dr. Hwang joined the NHLBI as a tenure-track investigator and became a senior investigator in the Cardiovascular Branch in 2011. He was elected as member of American Society for Clinical Investigation and fellow of the American College of Cardiology. He has served on the editorial boards of Drug Discovery Today, Frontiers in Mitochondrial Physiology, and Mitochondrion, and has authored numerous research articles and reviews in major journals. He has been recognized for his contributions to the NHLBI intramural research by receiving the NHLBI Orloff Science Award and the NHLBI Director’s Award for Outstanding Translational Science.