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		Search Text: Home/< Back ToThe Science/Obesity and Aging Research
  Obesity and Aging Research
    The primary research interest of the Laboratory of Obesity and Aging Research, led by Dr. Jay H. Chung, is understanding how aging and obesity affect energy metabolism and mitochondrial function and vice versa.
    On This Page
    
          jay chung
  Jay Chung, M.D., Ph.D.
          Senior Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              Dr. Chung's primary research interest is in understanding how metabolic (mitochondrial) dysfunction affects cellular physiology and leads to disease. Inflammation is at the root of a number of diseases associated with obesity and aging. An important source of ‘metabolic inflammation’ is the mitochondria. One effector of mitochondria-mediated inflammation is mitochondrial DNA (mtDNA) that is released into the cytosol and/or extra-cellular space, where it can activate the Type-I interferon response and autoimmunity. Dr. Chung’s group identified pores formed by the voltage-dependent anion channel (VDAC) oligomers on oxidatively-stressed mitochondria that promote mitochondrial outer membrane permeability (MOMP) in living cells and allow release of mtDNA. Since VDAC oligomerization is promoted by mitochondrial oxidative stress, VDAC oligomer-mediated MOMP links mitochondrial stress to inflammation. The observation that a VDAC oligomerization inhibitor ameliorates lupus-like disease in mice suggests that VDAC oligomers may be a target for treating other conditions associated with inflammation and autoimmunity.

One strategy for reducing the burden of stressed or damaged mitochondria is removing them via mitophagy, which is promoted under conditions of energy-deficiency, such as restricted feeding. A critical player in the salutary effects of restricted feeding is AMP-activated kinase, an energy sensor that is activated by energy-deficiency and promotes autophagy and mitophagy. Not surprisingly, AMPK is a major player in obesity and aging and as such, regulation of AMPK has been a major focus of Dr. Chung’s group. Along this line, Dr. Chung is developing novel treatment strategies to harness the benefits of restricted feeding without altering food intake by discovering novel small molecule drugs and biologicals.

As an endocrinologist, Dr. Chung has been interested in the “obesity-aging” paradox: an average American gains approximately 30 lbs in weight over 30 years in midlife, even though food intake decreases during this period.  The weight gain, which occurs primarily in the abdominal/visceral depot, is an important driver of many chronic diseases of Western society: type 2 diabetes, cardiovascular diseases and even cancer and Alzheimer’s disease. Dr. Chung’s group is interested in understanding how DNA-PK activity affects the aging-induced decline in metabolism and mitochondrial function and the role it has in chronic diseases associated with obesity and aging.
  Videos

            AlessioRed=mitochondria. Green=cytoplasmic mtDNA.
Featured Publications
                VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease.
            Authors:Kim J, Gupta R, Blanco LP, Yang S, Shteinfer-Kuzmine A, Wang K, Zhu J, Yoon HE, Wang X, Kerkhofs M, Kang H, Brown AL, Park SJ, Xu X, Zandee van Rilland E, Kim MK, Cohen JI, Kaplan MJ, Shoshan-Barmatz V, Chung JH.
                                                                                                                        
            Science
      
                2019 Dec 20;366(6472):1531-1536
        Read Publication
                      Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases.
            Authors:Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, Kim MK, Beaven MA, Burgin AB, Manganiello V, Chung JH
                                                                                                                        
            Cell
      
                2012 Feb 03;148(3):421-33
        Read Publication
                      Peptide switch is essential for Sirt1 deacetylase activity.
            Authors:Kang H, Suh JY, Jung YS, Jung JW, Kim MK, Chung JH
                                                                                                                        
            Mol. Cell
      
                2011 Oct 21;44(2):203-13
        Read Publication
                      DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging.
            Authors:Park SJ, Gavrilova O, Brown AL, Soto JE, Bremner S, Kim J, Xu X, Yang S, Um JH, Koch LG, Britton SL, Lieber RL, Philp A, Baar K, Kohama SG, Abel ED, Kim MK, Chung JH
                                                                                                                        
            Cell Metab
      
                2017 May 02;25(5):1135-1146.e7
        Read Publication
                      Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins.
            Authors:Kang H, Oka S, Lee DY, Park J, Aponte AM, Jung YS, Bitterman J, Zhai P, He Y, Kooshapur H, Ghirlando R, Tjandra N, Lee SB, Kim MK, Sadoshima J, Chung JH
                                                                                            
            Nat Commun
      
                2017 May 15;8:15560
        Read Publication
                                View More Publications
  Meet the Team

    jay chung

            Jay Chung, M.D., Ph.D.
                Senior Investigator
                Dr. Jay H. Chung earned his bachelor’s degrees in electrical engineering and computer science and biology from M.I.T. before receiving an M.D. and Ph.D. in genetics from Harvard Medical School, where he was awarded the James Tolbert Shipley Prize for Excellence in Research. After an internship and residency in internal medicine at the Brigham and Women’s Hospital, he became an endocrinology fellow at the National Institute of Diabetes and Digestive and Kidney Diseases at the NIH, where he trained with Gary Felsenfeld. He is currently a tenured senior investigator and chief of the Laboratory of Obesity and Aging Research in NHLBI. Dr. Chung has received numerous awards for his research, including the NHLBI Director’s Awards and Orloff Scientific Awards.
    
          Contact the lab
    10 Center DrBethesda, MD 20814United States
        Phone:
                    301-496-3075
                Fax:
            301-480-4557
  Alexandra Brown
    
            Alexandra Brown, Ph.D.
        

    Scientific Support Staff

        browna@nhlbi.nih.gov
            Shutong Yang
    
            Shutong Yang, M.D.
        

    Scientific Support Staff

        yangs@nhlbi.nih.gov
            Sung Jun Park
    
            Sung Jun Park, Ph.D.
        

    Staff Scientist

        parksj2@nhlbi.nih.gov
            Tianjiao Huang
    
            Tianjiao Huang, Ph.D.
        

    Postdoctoral Fellow

        tianjiao.huang@nih.gov
            Jeonghan Kim
    
            Jeonghan Kim, Ph.D.
        

    Postdoctoral Fellow

        jeonghan.kim@nih.gov
            Antoine Smith
    
            Antoine Smith
        

    Scientific Support Staff

        smitha@nhlbi.nih.gov
            photo of Jinsung Park
    
            Jinsung Park, Ph.D.
        

    Postdoctoral Fellow

        jinsung.park@nih.gov
            photo of Camille Krejkovsky
    
            Camille Krejkovsky
        

    Summer Intern
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