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

Dr. Hwang’s laboratory investigates the role of mitochondrial regulation and function on human health and disease. Their earlier work revealed that p53, a critical tumor suppressor often referred to as the “guardian of the genome,” promotes mitochondrial function as part of its redox activities (Matoba S et al., Science, 2006). This work further established links between p53-mediated mitochondrial regulation, exercise capacity, and protection against chemotherapy-induced heart failure. The laboratory subsequently found that heritable mutations of p53 associated with Li-Fraumeni syndrome (LFS), an early onset cancer disorder, can alter mitochondrial metabolism to contribute to tumorigenesis. Importantly, their studies demonstrated that targeting this altered mitochondrial metabolic state can suppress cancer formation, revealing a potential metabolic vulnerability for developing chemoprevention strategies.

More recently, Dr. Hwang’s laboratory identified endoplasmic reticulum (ER) stress-inducible WASF3 as a key mediator of mitochondrial dysfunction, impaired cellular bioenergetics, and p53 stress signaling in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This work provides new insights into the molecular mechanisms underlying the multisystem manifestations of ME/CFS, a debilitating and poorly understood chronic disease that may affect up to ~1% of the general population. In addition, the laboratory has identified a mitochondrial signaling pathway that regulates cardiac and skeletal muscle adaptation to increased workload and exercise, respectively. Activation of this pathway enhances fatty acid oxidation and protects against obesity, highlighting the broader role of mitochondrial function in maintaining metabolic health. Together, these mechanistic discoveries provide a foundation for ongoing human translational studies aimed at developing targeted strategies for cancer prevention, reducing the burden of disability associated with ME/CFS, and improving cardiovascular and metabolic 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.