Cardiovascular and Cancer Genetics
Earlier work in Dr. Hwang’s lab revealed that p53, the most commonly mutated tumor suppressor gene in human cancers that controls multiple pathways involved in cell growth, also regulates mitochondrial respiration as part of its adaptive activities against oxidative and other cellular stresses. Their work using mouse models as well as translational studies in patients with Li-Fraumeni syndrome (LFS), a cancer predisposition disorder caused by diverse inherited mutations in TP53, revealed that mutant p53 can have gain-of-function activities to promote oxidative metabolism and increase aerobic exercise capacity. Furthermore, they found that inhibiting mitochondrial metabolism can prevent tumorigenesis in LFS mouse models and that p53 can prevent chemotherapy-induced heart failure by maintaining the mitochondrial genome, both of which have important clinical implications. While continuing to examine the role of p53 in cardiac muscle homeostasis, they have recently identified a specific gene that regulates the mitochondria and appears to cause skeletal muscle bioenergetic deficiency in chronic fatigue syndrome. They have also identified a specific mitochondrial signaling pathway that mediates skeletal muscle adaptation to exercise, thereby increasing fatty acid oxidation and preventing obesity. The clinical relevance of these mechanistic insights are being determined through human translational studies with the potential to develop novel strategies for 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.
- Wang PY, Ma J, Kim YC, Son AY, Syed AM, Liu C, Mori MP, Huffstutler RD, Stolinski JL, Talagala SL, Kang JG, Walitt BT, Nath A, Hwang PM. WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2023;120(34):e2302738120.
- Li J, Wang PY, Long NA, Zhuang J, Springer DA, Zou J, Lin Y, Bleck CKE, Park JH, Kang JG, Hwang PM. p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities. Proc Natl Acad Sci U S A. 2019;116(39):19626-19634.
- Wang PY, Li J, Walcott FL, Kang JG, Starost MF, Talagala SL, Zhuang J, Park JH, Huffstutler RD, Bryla CM, Mai PL, Pollak M, Annunziata CM, Savage SA, Fojo AT, Hwang PM. Inhibiting mitochondrial respiration prevents cancer in a mouse model of Li-Fraumeni syndrome. J Clin Invest. 2017;127(1):132-136.
- Wang PY, Ma W, Park JY, Celi FS, Arena R, Choi JW, Ali QA, Tripodi DJ, Zhuang J, Lago CU, Strong LC, Talagala SL, Balaban RS, Kang JG, Hwang PM. Increased oxidative metabolism in the Li-Fraumeni syndrome. N Engl J Med. 2013;368(11):1027-32.
- Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM. p53 regulates mitochondrial respiration. Science. 2006;312(5780):1650-3.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on Thursday, August 31, 2023