About The Investigator

    Smita Ghare

    Smita Ghare, PhD
    Assistant Professor
    of Medicine
    Division of Gastroenterology, Hepatology & Nutrition


    Education

    • B.Sc.: Wilson College, University of Mumbai
    • M.Sc.: LTMM College, University of Mumbai
    • Ph.D.: University of Louisville

    Epigenetic Regulation of CC-(CCL2) and CXC-(CXCL2) Chemokines in the Pathogenesis of Alcoholic Liver Disease

    Alcoholic liver disease (ALD) is associated with high morbidity and mortality, and despite being actively investigated there is no FDA approved therapy.

    Overview

    Smita Ghare project dataEmerging evidence demonstrates that alcohol-induced chemokine up-regulation and hepatic leukocyte infiltration are important factors in the development of ALD. Alcohol-induced alterations in epigenetic mechanisms play a significant role in the development of ALD.

    Our preliminary data showed that ethanol increased histone H3 lysine9 (H3K9) acetylation levels at hepatic CCL2 promoter, and that a dietary HDAC inhibitor (tributyrin-a butyrate pro-drug) attenuated alcohol-induced CCL2 and CXCL2 expression, neutrophil infiltration and prevent hepatic inflammation and injury.

    This project will determine the molecular mechanisms underlying chronic alcohol-induced chemokine upregulation and will examine the potential of nutrition-based interventions that target HDAC inhibition.

    The results of this study will provide critical molecular insights and facilitate the development of therapeutic interventions for ALD.

    Hypothesis

    Chronic alcohol-induced alterations in hepatic HATs and HDACs drive pathogenic posttranslational modifications of histones and non-histone proteins upregulating CC- and CXC-chemokines expression contributing to liver inflammation and injury.