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    Chinmay M Trivedi MD, PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentMedicine
    AddressUniversity of Massachusetts Medical School
    368 Plantation Street
    Worcester MA 01605
    Phone508-856-6947
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentTranslational Science

        Overview 
        Narrative

        Heart disease, adult and congenital, is the leading cause of morbidity and mortality in the developed world due to inability of existing treatment to replace damaged and lost heart tissue. Heart is one of the least regenerative organs in the body with limited endogenous ability to repair or replace affected cardiomyocytes. The research goal of the Trivedi lab is to identify cellular processes and regulatory mechanisms involved in congenital heart diseases and thereby, cardiac growth and development. Mechanistic insights into embryonic cardiac growth pathways could pave the way to repair the injured embryonic and adult heart.

        Although transcription factors involved in cardiac growth and development have been described, the closely associated chromatin modifiers of this process remain largely unknown. Histone deacetylases (Hdacs) modify chromatin structure to regulate gene expression in the heart and elsewhere. Using knockout murine models and isolated cardiomyocytes, we have characterized chromatin modifying enzymes and signaling pathways leading to cardiomyocyte differentiation (Lewandowski SL et al, Human Molecular Genetics, 2014), proliferation (Trivedi CM et al, Developmental Cell, 2010; Trivedi CM et al, JBC, 2008) and hypertrophic cardiomyopathy (Trivedi CM et al, Nature Medicine, 2007).

        Recently, the Trivedi lab has established a critical interplay between chromatin modifying enzymes and transcription factors during pathogenesis of congenital heart defects (Lewandowski et al, Human Molecular Genetics, 2014). TBX5, the causative gene in the Holt-Oram Syndrome, was the first identified single-gene mutation giving rise to congenital heart defects. Our studies reveal a critical mechanistic relationship between TBX5G125R, a gain-of-function mutation identified in patients with Holt-Oram Syndrome, and Hdac3. We described a specific and novel function of Hdac3 in cardiac progenitor cells during early murine cardiogenesis. We uncover a mechanism whereby Hdac3 deacetylates the transcription factor Tbx5 and represses Tbx5-dependent activation of cardiomyocyte lineage-specific genes to maintain the pluripotent state of cardiac progenitor cells. These discoveries have opened new areas of investigation and contributed to growing appreciation that HDACs are master regulators of cardiomyocyte homeostasis and function.

         



        Rotation Projects

        Rotation Projects:

        Please contact Chinmay Trivedi (chinmay.trivedi@umassmed.edu) for information regarding potential rotation projects. We will develop a specific rotation project based on student's interest, background, and goals of the rotation. Students can rotate either for a half- or full-semester.

        Project 1: Characterize progressive lineage restriction of cardiac progenitor cells in murine model.
        Project 2: Identify novel chromatin modifiers regulating specification of murine cardiac progenitor cells. 
        Project 3: Characterize cellular interactions during murine cardiac development and diseases.
        Project 4: Determine novel roles of epigenetic modifications during cardiac diseases.


        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Kayyali US, Larsen CG, Bashiruddin S, Lewandowski SL, Trivedi CM, Warburton RR, Parkhitko AA, Morrison TA, Henske EP, Chekaluk Y, Kwiatkowski DJ, Finlay GA. Targeted deletion of Tsc1 causes fatal cardiomyocyte hyperplasia independently of afterload. Cardiovasc Pathol. 2014 Nov 7.
          View in: PubMed
        2. Lewandowski SL, Janardhan HP, Smee KM, Bachman M, Sun Z, Lazar MA, Trivedi CM. Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis. Hum Mol Genet. 2014 Jul 15; 23(14):3801-9.
          View in: PubMed
        3. Singh N, Gupta M, Trivedi CM, Singh MK, Li L, Epstein JA. Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression. Dev Biol. 2013 May 15; 377(2):333-44.
          View in: PubMed
        4. Banerjee A, Trivedi CM, Damera G, Jiang M, Jester W, Hoshi T, Epstein JA, Panettieri RA. Trichostatin A abrogates airway constriction, but not inflammation, in murine and human asthma models. Am J Respir Cell Mol Biol. 2012 Feb; 46(2):132-8.
          View in: PubMed
        5. Singh N, Trivedi CM, Lu M, Mullican SE, Lazar MA, Epstein JA. Histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and development of the cardiac outflow tract. Circ Res. 2011 Nov 11; 109(11):1240-9.
          View in: PubMed
        6. Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell. 2011 Apr 8; 8(4):376-88.
          View in: PubMed
        7. Pillai VB, Sundaresan NR, Samant SA, Wolfgeher D, Trivedi CM, Gupta MP. Acetylation of a conserved lysine residue in the ATP binding pocket of p38 augments its kinase activity during hypertrophy of cardiomyocytes. Mol Cell Biol. 2011 Jun; 31(11):2349-63.
          View in: PubMed
        8. Trivedi CM, Cappola TP, Margulies KB, Epstein JA. Homeodomain only protein x is down-regulated in human heart failure. J Mol Cell Cardiol. 2011 Jun; 50(6):1056-8.
          View in: PubMed
        9. Trivedi CM, Epstein JA. Heart-healthy hypertrophy. Cell Metab. 2011 Jan 5; 13(1):3-4.
          View in: PubMed
        10. Trivedi CM, Zhu W, Wang Q, Jia C, Kee HJ, Li L, Hannenhalli S, Epstein JA. Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation. Dev Cell. 2010 Sep 14; 19(3):450-9.
          View in: PubMed
        11. Chokas AL, Trivedi CM, Lu MM, Tucker PW, Li S, Epstein JA, Morrisey EE. Foxp1/2/4-NuRD interactions regulate gene expression and epithelial injury response in the lung via regulation of interleukin-6. J Biol Chem. 2010 Apr 23; 285(17):13304-13.
          View in: PubMed
        12. Zhu W, Trivedi CM, Zhou D, Yuan L, Lu MM, Epstein JA. Inpp5f is a polyphosphoinositide phosphatase that regulates cardiac hypertrophic responsiveness. Circ Res. 2009 Dec 4; 105(12):1240-7.
          View in: PubMed
        13. Kerkela R, Kockeritz L, Macaulay K, Zhou J, Doble BW, Beahm C, Greytak S, Woulfe K, Trivedi CM, Woodgett JR, Epstein JA, Force T, Huggins GS. Deletion of GSK-3beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. J Clin Invest. 2008 Nov; 118(11):3609-18.
          View in: PubMed
        14. Trivedi CM, Lu MM, Wang Q, Epstein JA. Transgenic overexpression of Hdac3 in the heart produces increased postnatal cardiac myocyte proliferation but does not induce hypertrophy. J Biol Chem. 2008 Sep 26; 283(39):26484-9.
          View in: PubMed
        15. Trivedi CM, Patel RC, Patel CV. Differential regulation of HOXA9 expression by nuclear factor kappa B (NF-kappaB) and HOXA9. Gene. 2008 Jan 31; 408(1-2):187-95.
          View in: PubMed
        16. Trivedi CM, Patel RC, Patel CV. Homeobox gene HOXA9 inhibits nuclear factor-kappa B dependent activation of endothelium. Atherosclerosis. 2007 Dec; 195(2):e50-60.
          View in: PubMed
        17. Trivedi CM, Luo Y, Yin Z, Zhang M, Zhu W, Wang T, Floss T, Goettlicher M, Noppinger PR, Wurst W, Ferrari VA, Abrams CS, Gruber PJ, Epstein JA. Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Nat Med. 2007 Mar; 13(3):324-31.
          View in: PubMed
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