Cardiovascular and Cancer Genetics

The goal of Dr. Hwang's translational work is to provide insights into developing novel strategies for preventing cancer and improving cardiovascular health.

On This Page
Hwang

Research Interests

Research Interests

Cardiovascular and Cancer Genetics

TP53, encoding tumor protein p53, is the one of the most commonly mutated tumor suppressor genes in cancer and a key transcriptional regulator of multiple programs that control cell growth. 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. Their subsequent findings suggested that p53 regulates mitochondrial metabolism through multiple pathways as part of its adaptive activities against oxidative and other cellular stresses. The research group is continuing to focus on this link between cancer and mitochondrial metabolism, which also impacts the cardiovascular system, by using mouse models as well as by performing translational studies in patients with Li-Fraumeni syndrome (LFS), a cancer predisposition disorder caused by diverse germline mutations in TP53. Ongoing work shows that modulating mitochondrial metabolism can affect tumorigenesis in a mouse model of LFS and that p53 plays a protective role against chemotherapy-induced heart failure, both of which may have important clinical implications. The goal of their study on mitochondrial metabolism in model systems is to determine their relevance to human diseases through translational studies and to develop new strategies for cancer prevention and cardiovascular health.

Featured Publications

A mouse homolog of a human TP53 germline mutation reveals a lipolytic activity of p53.

Authors: Kang JG, Lago CU, Lee JE, Park JH, Donnelly MP, Starost MF, Liu C, Kwon J, Noguchi AC, Ge K, Wang PY, Hwang PM.
Cell Rep. 2020 Jan 21;30(3):783-792
Read Publication

p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities.

Authors: Li J, Wang PY, Long NA, Zhuang J, Springer DA, Zou J, Lin Y, Bleck CKE, Park JH, Kang JG, Hwang PM.
Proc Natl Acad Sci USA 2019 Sep 24;116(39):19626-19634
Read Publication

Mouse homolog of the human TP53 R337H mutation reveals its role in tumorigenesis.

Authors: Park JH, Li J, Starost MF, Liu C, Zhuang J, Chen J, Achatz MI, Kang JG, Wang PY, Savage SA, Hwang PM
Cancer Res 2018 Sep 15;78(18):5375-5383
Read Publication
Related Labs: Transgenic Core

Inhibiting mitochondrial respiration prevents cancer in a mouse model of Li-Fraumeni syndrome.

Authors: 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
J Clin Invest 2017 Jan 03;127(1):132-136
Read Publication

Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise

Authors: Zhuang J, Kamp WM, Li J, Liu C, Kang JG, Wang PY, Hwang PM
J Biol Chem 2016 Nov 25;291(48):24819-24827
Read Publication

Meet the Team

Hwang

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

Senior Investigator

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.

View Hwang's Profile
Ju-Gyeong Kang

Ju-Gyeong Kang, Ph.D.

Staff Scientist
Ping-yuan Wang

Ping-yuan Wang, Ph.D.

Staff Scientist
Jin Ma

Jin Ma, PhD

Postdoctoral Fellow
Mateus Mori

Mateus Mori, PhD

Postdoctoral Fellow
Masahiro Nishi

Masahiro Nishi, PhD

Postdoctoral Fellow