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		Search Text: Home/< Back ToThe Science/Cardiovascular and Cancer Genetics
  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
    
          Paul Hwang, M.D., Ph.D.
  Paul Hwang, M.D., Ph.D.
          Senior Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              **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.
  Featured Publications
                WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome
            Authors: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
                                                                                                                        
            Proc Natl Acad Sci U S A
      
                2023 Aug 14;120(34):
        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
                      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
                      Increased oxidative metabolism in the Li-Fraumeni syndrome.
            Authors: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.
                                                                                                                        
            N Engl J Med
      
                2013 Mar 14;368(11):1027-32
        Read Publication
                      p53 regulates mitochondrial respiration.
            Authors:Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM
                                                                                                                        
            Science
      
                2006 Jun 16;312(5780):1650-3
        Read Publication
                                View More Publications
  Meet the Team

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

            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.
    
          Contact the lab
    10 Center DrBethesda, MD 20814United States
        Phone:
                Fax:
  Kim
    
            Young-Chae Kim, Ph.D.
        

    Staff Scientist

        young-chae.kim@nih.gov
            Ping-yuan
    
            Ping-yuan Wang, Ph.D.
        

    Staff Scientist

        wangp4@mail.nih.gov
            Jin Ma
    
            Jin Ma, Ph.D.
        

    Postdoctoral Fellow

        jin.ma@nih.gov
            Abu Syed, PhD
    
            Abu Syed, Ph.D.
        

    Postdoctoral Fellow

        abu.syed@nih.gov
            Annie Son
    
            Annie Son, B.A.
        

    Postbaccalaureate Fellow

        annie.son@nih.gov
            Alexander Karius
        

    Postbaccalaureate Fellow

        alexander.karius@nih.gov
  
  Alumni
        

Satoaki Matoba, M.D., Ph.D.
        

    Postdoctoral Fellow
        Satoaki Matoba, M.D., Ph.D. is currently a Professor and Chair at Cardiology Department, Kyoto Prefectural University of Medicine.
      Joon-Young Park, Ph.D.
        

    Postdoctoral Fellow
        Joon-Young Park, Ph.D. is currently a Associate Professor at Department of Health, Baylor University, Waco, Texas.
      Jie Zhuang, Ph.D.
        

    Postdoctoral Fellow
        Jie Zhuang, Ph.D. is currently a Associate Professor at Nankai University Medical School, Tianjin, China.
      Ju Gyeong Kang, Ph.D.
        

    Postdoctoral Fellow
        Ju Gyeong Kang, Ph.D. is currently a Research Professor at Laoratory of Molecular Oncogenetics, Korea Advanced Institute of Science and Technology. Back To Top Link
  

        

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