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    Yong Xu Wang PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB-517
    Worcester MA 01605
    Phone508-856-5647
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Gene Function and Expression

        Overview 
        Narrative

        Academic Background

        Yong-Xu Wang received his B.S. in 1989 from Peking University, China, and his Ph.D. in 1999 from the University of Iowa.  He was a postdoctoral fellow at the Salk Institute from 1999 to 2004.  He joined the Program in Gene Function and Expression at the University of Massachusetts Medical School as an Assistant Professor in February 2005.

        Transcriptional Control of Energy Metabolism and Metabolic Diseases by the Nuclear Receptor PPAR Subfamily

        Photo: Yong-Xu Wang, Ph.D.

        Normal cellular energy metabolism is maintained through a delicate balance between energy intake and energy expenditure.  When energy intake exceeds energy expenditure, the extra energy is stored in the form of fat.  This energy imbalance is intimately linked to a cluster of metabolic diseases, including obesity, hyperlipidemia, and cardiovascular disease, as well as insulin resistance and type 2 diabetes.  Our laboratory is interested in understanding the transcriptional control of fatty acid and glucose metabolism by the PPAR subfamily of nuclear receptors.  PPARs are transcription factors and their activities can be regulated by dietary lipids and small synthetic compounds.  The three PPAR members (a, g, and d) display distinct tissue distribution profiles and together they control diverse metabolic processes, ranging from adipogenesis, lipogenesis, and lipid storage to oxidative metabolism.  Thus, these receptors serve as central molecular switches in metabolic regulation and are ideal drug targets for metabolic diseases.

        We have recently demonstrated that PPARd powerfully promotes fat burning both in vivo and in cultured cells by activating multiple, coordinated programs involved in mitochondrial biogenesis, ß-oxidation, electron transfer chain, and energy uncoupling.  As a result, mice with an activated form of PPARd, or those treated with a PPARd agonist, are resistant to obesity and to insulin resistance and glucose intolerance induced by a high-fat diet. 

        In a related study, we have investigated the role of PPARd in muscle fiber plasticity.  Skeletal muscle fibers are generally classified as either slow twitch (red muscle) or fast twitch (white muscle).  Slow twitch fibers are more fatigue-resistant than fast twitch fibers.  Endurance exercise training can provoke adaptive changes that convert fast twitch to slow twitch fibers.  We have found that simply expressing an activated form of PPARd in the skeletal muscle leads to a switch from fast twitch to slow twitch fibers, essentially mimicking the effects of endurance exercise training.  Functionally, the transgenic mice are able to run twice the distance of normal mice.  These data provide important molecular insight into the transcriptional control of muscle fiber plasticity pertinent to exercise training.  

        Our current focus is to further dissect the functional roles of PPARs in normal physiology and metabolic diseases in a variety of metabolically active tissues, to understand the molecular mechanisms of their action, and to investigate their interactions with environmental factors and other signaling events.  A combination of tools, including molecular biology, mouse genetics, physiology and genomics, will be employed.

        Figure

         

        Yong-Xu Wang Figure

        Shown are gastrocnemius muscles from a wild type mouse (WT) and a transgenic mouse (TG) expressing an activated form of PPARd .  The red color in the transgenic muscle is due to increased type I muscle fibers.



        Rotation Projects

        Potential Rotation Projects

        1.Roles of PPARd in metabolic diseases
        2.Functional requirement of the transcriptional co-activator PGC-1 in PPAR activation
        3.Modulation of PPAR activity by signaling pathways



        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Wang for additional details.



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Pan D, Mao C, Wang YX. Suppression of gluconeogenic gene expression by LSD1-mediated histone demethylation. PLoS One. 2013; 8(6):e66294.
          View in: PubMed
        2. Pan D, Mao C, Zou T, Yao AY, Cooper MP, Boyartchuk V, Wang YX. The histone demethylase Jhdm1a regulates hepatic gluconeogenesis. PLoS Genet. 2012; 8(6):e1002761.
          View in: PubMed
        3. Wei P, Pan D, Mao C, Wang YX. RNF34 is a cold-regulated E3 ubiquitin ligase for PGC-1a and modulates brown fat cell metabolism. Mol Cell Biol. 2012 Jan; 32(2):266-75.
          View in: PubMed
        4. Angione AR, Jiang C, Pan D, Wang YX, Kuang S. PPARd regulates satellite cell proliferation and skeletal muscle regeneration. Skelet Muscle. 2011; 1(1):33.
          View in: PubMed
        5. Wang YX. PPARs: diverse regulators in energy metabolism and metabolic diseases. Cell Res. 2010 Feb; 20(2):124-37.
          View in: PubMed
        6. Pan D, Fujimoto M, Lopes A, Wang YX. Twist-1 is a PPARdelta-inducible, negative-feedback regulator of PGC-1alpha in brown fat metabolism. Cell. 2009 Apr 3; 137(1):73-86.
          View in: PubMed
        7. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008 Aug 8; 134(3):405-15.
          View in: PubMed
        8. Shalom-Barak T, Nicholas JM, Wang Y, Zhang X, Ong ES, Young TH, Gendler SJ, Evans RM, Barak Y. Peroxisome proliferator-activated receptor gamma controls Muc1 transcription in trophoblasts. Mol Cell Biol. 2004 Dec; 24(24):10661-9.
          View in: PubMed
        9. Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, Bayuga-Ocampo CR, Ham J, Kang H, Evans RM. Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol. 2004 Oct; 2(10):e294.
          View in: PubMed
        10. Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med. 2004 Apr; 10(4):355-61.
          View in: PubMed
        11. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell. 2003 Apr 18; 113(2):159-70.
          View in: PubMed
        12. Wang YX, Kauffman EJ, Duex JE, Weisman LS. Fusion of docked membranes requires the armadillo repeat protein Vac8p. J Biol Chem. 2001 Sep 14; 276(37):35133-40.
          View in: PubMed
        13. Wang YX, Catlett NL, Weisman LS. Vac8p, a vacuolar protein with armadillo repeats, functions in both vacuole inheritance and protein targeting from the cytoplasm to vacuole. J Cell Biol. 1998 Mar 9; 140(5):1063-74.
          View in: PubMed
        14. Wang YX, Zhao H, Harding TM, Gomes de Mesquita DS, Woldringh CL, Klionsky DJ, Munn AL, Weisman LS. Multiple classes of yeast mutants are defective in vacuole partitioning yet target vacuole proteins correctly. Mol Biol Cell. 1996 Sep; 7(9):1375-89.
          View in: PubMed
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