Dr. Paul Hwang earned a B.A. 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 M.D. and Ph.D 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 in the Cardiovascular Branch. In 2011 he became a senior investigator in NHLBI's Center for Molecular Medicine. 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 or coauthored more than 70 publications.
TP53 that encodes the tumor suppressor protein p53 is one of the most commonly mutated genes in cancer and a key transcriptional regulator of multiple genetic programs that control cell growth and death. Earlier work in Dr. Hwang’s lab revealed that p53 also regulates mitochondrial respiration by controlling the assembly of the enzyme complex that consumes molecular oxygen to produce cellular energy. This link between cancer and mitochondrial energetics has brought Dr. Hwang's research to the intersection of cancer and cardiovascular biology, where he has explored the role of mitochondrial function in normal and abnormal cellular processes.
Oxidative stress has received a great deal of attention in recent years as a cause of a variety of human diseases. Mitochondria, which are the center of cellular oxygen consumption, have been thought to be the source of reactive oxygen species generation. Instead, Dr. Hwang’s study indicates that mitochondria are part of the solution imposed by evolution to facilitate life in an oxygen rich environment. They not only provide energy but also protect the cell from an overabundance of reactive molecular oxygen. For example, he and his colleagues have shown that cells lacking SCO2 (Synthesis of Cytochrome c Oxidase 2)—a gene regulated by p53 and essential for eukaryotic oxygen consumption—have paradoxically increased levels of oxidative DNA damage and that decreasing ambient oxygen exposure delays de novo tumorigenesis. As such, p53's regulation of mitochondrial bioenergetics may be part of its overall function to maintain genomic integrity in an oxidizing environment.
Many human observational studies have reported an inverse relationship between exercise capacity and cancer. Mice deficient in p53 are prone to develop cancer and display a dramatic gene dose-dependent decrease in aerobic exercise capacity, suggesting that the metabolic biology of p53 may be a link between cardiovascular fitness and cancer. Dr. Hwang is currently bringing these observations into the clinic by studying metabolism in patients with Li-Fraumeni syndrome (LFS), a condition caused by a diverse set of germ-line mutations in TP53 that predispose to multiple forms of cancer. The hope is that the results of his basic and translational work may provide insights into developing novel strategies for preventing cancer and improving cardiovascular health.