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Chinmay M Trivedi MD, PhD

InstitutionUMass Chan Medical School
AddressUMass Chan Medical School
368 Plantation Street
Worcester MA 01605
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DivisionCardiovascular Medicine

    InstitutionT.H. Chan School of Medicine
    DepartmentMolecular, Cell and Cancer Biology

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentTranslational Science

    Collapse Overview 
    Collapse overview

    The research goal of Dr. Trivedi’s laboratory is to identify causal mechanisms of congenital cardiac and vascular diseases affecting human patients. Our discoveries have uncovered essential roles of chromatin-modifying enzymes and signaling pathways in the pathogenesis of human diseases such as Emberger syndrome - Lymphedema (The Journal of Clinical Investigation), Noonan syndrome - Chylothorax and Lymphangiectasia (JCI Insight), Holt-Oram syndrome (Human Molecular Genetics), Hepatic cavernous hemangiomas (Journal of Experimental Medicine), Aortic stenosis (JBC), Epithelioid hemangioendothelioma (ATVB), Mitochondrial disease (Science Advances), Congenital heart disease (Developmental Cell, JBC), Craniofacial anomalies (Developmental Dynamics), and Hypertrophic cardiomyopathy (Nature Medicine). These discoveries have opened new areas of investigation, identified fundamental developmental processes, and contributed to a roadmap for novel therapies.

    Emberger syndrome (Lymphedema) is a lymphatic anomaly, and it is responsible for considerable morbidity, with no current effective treatments. The underlying pathology is often defective lymphatic valve development leading to improper drainage of extravasated protein-rich fluid from the tissues. Recently we revealed how human genetic variants or mutations within evolutionarily conserved non-coding DNA elements alter recruitment of histone deacetylase 3 (Hdac3), thus modifying gene expression to cause lymphedema (The Journal of Clinical Investigation). Our study demonstrates that Hdac3 is essential for lymphatic valve development, thus lymphatic drainage in mice. Hdac3-deficient lymphatic valves exhibit reduced expression of Gata2, which is frequently mutated in patients with Emberger syndrome. In response to extracellular oscillatory shear stress (OSS), Hdac3 functions in a chromatin-dependent, but deacetylase-independent, manner to activate Gata2 expression within lymphatic endothelial cells (LECs), the building blocks of the mammalian lymphatic valves. Mechanistically, the transcription factors Tal1, Gata2, and Ets1/2 physically interacted with and recruited Hdac3 to the evolutionarily conserved (divergence ~350 million years ago) E-box–GATA–ETS composite element of a Gata2 intragenic enhancer in response to OSS. In turn, Hdac3 recruited histone acetyltransferase Ep300 to form an enhanceosome complex that promoted Gata2 expression. Interestingly, mutations within this conserved GATA2 intragenic enhancer reduce GATA2 expression and cause lymphedema (Emberger syndrome) in both humans and mice. These data challenge long-held assumptions that HDACs replace HATs to promote both histone deacetylation and repression of transcription.

    Hepatic vascular cavernomas, the most common benign tumor of the liver, cause lethal complications such as hepatic rupture, consumption coagulopathy, and cardiac failure. Although Virchow and Frerichs described hepatic vascular cavernomas as a distinct clinical entity in the mid-1800s, their genetic etiology, molecular mechanism, and effective treatment remain undefined. Recently we identified gain-of-function mutations in KRAS or BRAF genes within liver endothelial cells as a causal mechanism for hepatic vascular cavernomas (Journal of Experimental Medicine). We identified gain-of-function mutations in KRAS or BRAF genes in pathological liver tissue samples from patients with hepatic vascular cavernomas. Mice expressing this human KRASG12D or BRAFV600E gain-of-function mutations in hepatic endothelial cells recapitulated the human hepatic vascular cavernoma phenotype of dilated sinusoidal capillaries with defective branching patterns. KRASG12D or BRAFV600E induced “zipper-like” contiguous expression of junctional proteins at sinusoidal endothelial cell-cell contacts, switching capillaries from branching to cavernous expansion. Pharmacological or genetic inhibition of the endothelial RAS–MAPK1 signaling pathway rescued hepatic vascular cavernoma formation in endothelial KRASG12D- or BRAFV600E-expressing mice. These results uncover a major cause of hepatic vascular cavernomas and provide a road map for their personalized treatment.

    Our recent study identifies a causal relationship between Congenital Heart Disease (CHD), the most common developmental defect in children, and defective developmental energy generation (Science Advances). We demonstrated that two class I histone deacetylases, Hdac1 and Hdac2, silence cryptic transcription to promote mitochondrial function in developing murine hearts. Cryptic transcription is observed in lower organisms and mammalian cell lines, yet no reports describe cryptic transcription in a vertebrate system. This report is the first link between chromatin-modifying enzymes and cryptic transcription during vertebrate development and the first to link cryptic transcription and energy production during cardiogenesis.

    Collapse Rotation Projects

    Rotation Projects:

    Please contact Chinmay Trivedi (chinmay.trivedi@umassmed.edu) for information regarding potential rotation projects (for details - research performed by graduate students in the trivedi lab: The Journal of Clinical Investigation, Science Advances, Journal of Experimental Medicine, JCI InsightATVB, Human Molecular Genetics, Journal of Biological Chemistry).

    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.

    Collapse Post Docs

    A Postdoctoral position is available in the Trivedi lab to study roles of novel chromatin and epigenetic modifications during cardiovascular development and disease (for details of our research: The Journal of Clinical Investigation, Science Advances, Journal of Experimental Medicine, ATVBHuman Molecular Genetics, Journal of Biological Chemistry). Candidates with a PhD in Biochemistry, Molecular Biology, Stem Cell Biology or Developmental Biology are encouraged to apply. Previous experience with mice handling and biochemistry-molecular biology-epigenetics related techniques such as ChIP-seq is strongly desired. Candidate will be required to learn new techniques in the area of translational biology to advance their project.

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    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Bazzone LE, Zhu J, King M, Liu G, Guo Z, MacKay CR, Kyawe PP, Qaisar N, Rojas-Quintero J, Owen CA, Brass AL, McDougall W, Baer CE, Cashman T, Trivedi CM, Gack MU, Finberg RW, Kurt-Jones EA. ADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection. Nat Commun. 2024 May 16; 15(1):4153. PMID: 38755212.
    2. Gao KM, Chiang K, Jiang Z, Korkmaz FT, Janardhan HP, Trivedi CM, Quinton LJ, Gingras S, Fitzgerald KA, Marshak-Rothstein A. Endothelial cell expression of a STING gain-of-function mutation initiates pulmonary lymphocytic infiltration. Cell Rep. 2024 Apr 15; 43(4):114114. PMID: 38625791.
    3. Jung R, Trivedi CM. Unveiling the Spatiotemporal Diversity of the Endothelium in Development: A Multi-Omics Approach. Circ Res. 2024 03; 134(5):547-549. PMID: 38422180.
    4. Cashman TJ, Fitzgibbons TP, Trivedi CM. Integrated Pathogenesis of Vascular and Cardiac Valve Disease. Circ Res. 2023 09; 133(6):481-483. PMID: 37651543.
      Citations:    Fields:    Translation:Humans
    5. Gao KM, Chiang K, Korkmaz FT, Janardhan HP, Trivedi CM, Quinton LJ, Gingras S, Fitzgerald KA, Marshak-Rothstein A. Expression of a STING Gain-of-function Mutation in Endothelial Cells Initiates Lymphocytic Infiltration of the Lungs. bioRxiv. 2023 Jul 27. PMID: 37547024.
    6. Cashman TJ, Trivedi CM. Chromatin Compaction in Noncompaction Cardiomyopathy. Circ Res. 2023 06 23; 133(1):68-70. PMID: 37347831.
      Citations:    Fields:    Translation:HumansCells
    7. Park G, Haley JA, Le J, Jung SM, Fitzgibbons TP, Korobkina ED, Li H, Fluharty SM, Chen Q, Spinelli JB, Trivedi CM, Jang C, Guertin DA. Quantitative analysis of metabolic fluxes in brown fat and skeletal muscle during thermogenesis. Nat Metab. 2023 07; 5(7):1204-1220. PMID: 37337122.
      Citations: 5     Fields:    Translation:Animals
    8. Janardhan HP, Jung R, Trivedi CM. Lymphatic System in Organ Development, Function, and Regeneration. Circ Res. 2023 04 28; 132(9):1181-1184. PMID: 37104565.
      Citations: 1     Fields:    
    9. Janardhan HP, Dresser K, Hutchinson L, Trivedi CM. Pathological MAPK activation-mediated lymphatic basement membrane disruption causes lymphangiectasia that is treatable with ravoxertinib. JCI Insight. 2022 09 08; 7(17). PMID: 36073544.
      Citations: 3     Fields:    Translation:HumansAnimalsCells
    10. Jung R, Janardhan HP, Trivedi CM. Cation Channelopathies: Novel Insights into Generalized Lymphatic Dysplasia. Circ Res. 2022 07 08; 131(2):130-132. PMID: 35861738.
      Citations:    Fields:    Translation:Humans
    11. Cashman TJ, Trivedi CM. Human 3p14.3: A Regulatory Region in Transposition of the Great Arteries. Circ Res. 2022 01 21; 130(2):181-183. PMID: 35050689.
      Citations:    Fields:    Translation:HumansCells
    12. Jung R, Janardhan HP, Dresser K, Cotton JL, Hutchinson L, Mao J, Trivedi CM. Response by Jung et al to Letter Regarding Article, "Sustained Activation of Endothelial YAP1 Causes Epithelioid Hemangioendothelioma". Arterioscler Thromb Vasc Biol. 2021 10; 41(10):e493-e495. PMID: 34550712.
      Citations:    Fields:    Translation:Humans
    13. Cashman TJ, Trivedi CM. Extracardiac Progenitors: Moving Beyond the First and Second Heart Field. Circ Res. 2021 08 06; 129(4):488-490. PMID: 34351798.
      Citations:    Fields:    
    14. Janardhan HP, Saheera S, Jung R, Trivedi CM. Vascular and Lymphatic Malformations: Perspectives From Human and Vertebrate Studies. Circ Res. 2021 06 25; 129(1):131-135. PMID: 34166069.
      Citations: 7     Fields:    Translation:HumansAnimals
    15. Jung R, Janardhan HP, Dresser K, Cotton JL, Hutchinson L, Mao J, Trivedi CM. Sustained Activation of Endothelial YAP1 Causes Epithelioid Hemangioendothelioma. Arterioscler Thromb Vasc Biol. 2021 07; 41(7):2233-2235. PMID: 34078092.
      Citations: 2     Fields:    Translation:HumansAnimalsCells
    16. Cashman TJ, Trivedi CM. N-Acetyl Transferases: New Insights Into Human Congenital Cardiovascular Defects. Circ Res. 2021 04 16; 128(8):1170-1172. PMID: 33856919.
      Citations: 1     Fields:    Translation:Humans
    17. Cashman TJ, Trivedi CM. Super Enhancers: Enhancing Human Cardiogenesis. Circ Res. 2020 10 09; 127(9):1156-1158. PMID: 33031028.
      Citations: 2     Fields:    Translation:HumansCells
    18. Janardhan HP, Meng X, Dresser K, Hutchinson L, Trivedi CM. KRAS or BRAF mutations cause hepatic vascular cavernomas treatable with MAP2K-MAPK1 inhibition. J Exp Med. 2020 07 06; 217(7). PMID: 32405640.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    19. Milstone ZJ, Saheera S, Bourke LM, Shpilka T, Haynes CM, Trivedi CM. Histone deacetylases 1 and 2 silence cryptic transcription to promote mitochondrial function during cardiogenesis. Sci Adv. 2020 04; 6(15):eaax5150. PMID: 32300642.
      Citations: 5     Fields:    Translation:AnimalsCells
    20. Freedman JE, Trivedi CM. The Adverse Vascular Effects of E-Cigarettes: Smoke Without the Fire. J Am Coll Cardiol. 2019 06 04; 73(21):2738-2739. PMID: 31146819.
      Citations:    Fields:    Translation:HumansCells
    21. Janardhan HP, Trivedi CM. Establishment and maintenance of blood-lymph separation. Cell Mol Life Sci. 2019 May; 76(10):1865-1876. PMID: 30758642.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    22. Acharya D, Nera B, Milstone ZJ, Bourke L, Yoon Y, Rivera-P?rez JA, Trivedi CM, Fazzio TG. TIP55, a splice isoform of the KAT5 acetyltransferase, is essential for developmental gene regulation and organogenesis. Sci Rep. 2018 10 08; 8(1):14908. PMID: 30297694.
      Citations: 2     Fields:    Translation:AnimalsCells
    23. Zelic M, Roderick JE, O'Donnell JA, Lehman J, Lim SE, Janardhan HP, Trivedi CM, Pasparakis M, Kelliher MA. RIP kinase 1-dependent endothelial necroptosis underlies systemic inflammatory response syndrome. J Clin Invest. 2018 05 01; 128(5):2064-2075. PMID: 29664014.
      Citations: 38     Fields:    Translation:AnimalsCells
    24. Janardhan HP, Milstone ZJ, Shin M, Lawson ND, Keaney JF, Trivedi CM. Hdac3 regulates lymphovenous and lymphatic valve formation. J Clin Invest. 2017 Nov 01; 127(11):4193-4206. PMID: 29035278.
      Citations: 26     Fields:    Translation:HumansAnimalsCells
    25. Milstone ZJ, Lawson G, Trivedi CM. Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis. Dev Dyn. 2017 12; 246(12):1015-1026. PMID: 28791750.
      Citations: 8     Fields:    Translation:Animals
    26. Lewandowski SL, Janardhan HP, Trivedi CM. Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of Transforming Growth Factor-?1 (TGF-?1) to Orchestrate Second Heart Field Development. J Biol Chem. 2015 Nov 06; 290(45):27067-27089. PMID: 26420484.
      Citations: 42     Fields:    Translation:HumansAnimalsCells
    27. Jain R, Barkauskas CE, Takeda N, Bowie EJ, Aghajanian H, Wang Q, Padmanabhan A, Manderfield LJ, Gupta M, Li D, Li L, Trivedi CM, Hogan BLM, Epstein JA. Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung. Nat Commun. 2015 Apr 13; 6:6727. PMID: 25865356.
      Citations: 150     Fields:    Translation:HumansAnimalsCells
    28. 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. 2015 Mar-Apr; 24(2):80-93. PMID: 25434723.
      Citations: 4     Fields:    Translation:AnimalsCells
    29. 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. PMID: 24565863.
      Citations: 20     Fields:    Translation:HumansAnimalsCells
    30. 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. PMID: 23506836.
      Citations: 23     Fields:    Translation:AnimalsCells
    31. 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. PMID: 22298527.
      Citations: 39     Fields:    Translation:HumansAnimals
    32. 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. PMID: 21959220.
      Citations: 28     Fields:    Translation:Animals
    33. 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 08; 8(4):376-88. PMID: 21474102.
      Citations: 560     Fields:    Translation:HumansAnimalsCells
    34. 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. PMID: 21444723.
      Citations: 26     Fields:    Translation:HumansAnimalsCells
    35. 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. PMID: 21382376.
      Citations: 13     Fields:    Translation:HumansAnimalsCells
    36. Trivedi CM, Epstein JA. Heart-healthy hypertrophy. Cell Metab. 2011 Jan 05; 13(1):3-4. PMID: 21195341.
      Citations: 3     Fields:    
    37. 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. PMID: 20833366.
      Citations: 76     Fields:    Translation:AnimalsCells
    38. 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. PMID: 20185820.
      Citations: 34     Fields:    Translation:HumansAnimalsCells
    39. 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 04; 105(12):1240-7. PMID: 19875726.
      Citations: 39     Fields:    Translation:HumansAnimals
    40. 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. PMID: 18830417.
      Citations: 135     Fields:    Translation:AnimalsCells
    41. 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. PMID: 18625706.
      Citations: 61     Fields:    Translation:AnimalsCells
    42. 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. PMID: 18068911.
      Citations: 21     Fields:    Translation:HumansCells
    43. 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. PMID: 17586512.
      Citations: 23     Fields:    Translation:HumansCells
    44. 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. PMID: 17322895.
      Citations: 229     Fields:    Translation:AnimalsCells
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