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Gokul C. Das

Gokul C. Das

Texas Biomedical Research Institute
USA.

Title: Chronic Hepatitis C Virus infection and insulin resistance: molecular basis and potential therapeutic approaches

Biography

Dr Gokul C Das is currently a member of the faculty in the Department of Medicine, of the Center for AIDS research, Center for Drug Discovery and of the Dan L Duncan Cancer Center at the Baylor College of Medicine (BCM), Houston. Previously,he was a professor of molecular biology at the University of Texas Health Science Center at Tyler (UTHSCT). Dr Das had his Ph.D. degree in Biophysics from the University of Kolkata, India. After his postdoctoral work at the Institute de Biologie Moleculaire et Cellulaire du CNRS, Strasbourg, France and at the Oak Ridge National Laboratory, Oak Ridge, TN, he was a visiting scientist at NIH working on DNA tumor viruses. He continued his interest as a Professor of Molecular Biology at UTHCT. His Current interest is to understand molecular pathways in pathogenesis induced by Hepatitis C Virus (HCV) and HIV, or in HCV-HIV co-infection, and to use both a cellular and humanized animal model to develop antiviral strategies. Dr Das is currently on the editorial board of a number of international journals. He was the receipient of international guest scientist awards (1997,2000) from the Ministry of Science and Technology, Japan and was a member of the biotechnology delegation to China. .

Abstract

Hepatitis C virus (HCV) infection is a global health care problem affecting over 200 million individuals without any effective therapy and vaccine. In addition to a spectrum of liver diseases, chronic infection induces insulin resistance (IR) leading to metabolic syndrome and type 2 diabetes (T2DM) by dysregulating insulin signaling pathway(s). Development of IR not only accelerates the progression of liver disease, but also makes IFN-based therapy less-responsive. Thus understanding of the molecular basis of IR and non- response to therapy is pivotal for novel therapeutic development. Our central hypothesis is that both insulin receptor substrates (IRS-1 and IRS-2) are involved in dysregulation of insulin signaling by two entirely different mechanisms, the former through Ser 312 phosphorylation and the latter through down regulation by mi RNAs. Our major findings are: a) metabolic pathways for glucose homeostasis, insulin signaling and autophagy are dysregulated and they interact to contribute to IR, b) autophagy inhibitor Beclin-1 and energy sensors AMPK and mTOR are hyper- phosphorylated which is inhibited by IFNα, c) pathways leading to IR is activated within two weeks after infection, d) has-let 7 family of miRNAs are upregulated and target IRS-2, but these are down regulated in IFN treated cells. Our results suggest that strategies aimed at inactivating multiple pathways combinatorial effect of down regulating IRS-1 pathways and miRNA regulation of IRS-2 may lead to a better therapeutic outcome

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