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Research Scientist Lipid Research Laboratory Veterans Health Administration Medical Center

Chronic Ethanol Consumption: Understanding The Mechanisms Of Ethanol-induced Hepatic Steatosis And Ethanol-induced Regulation Of Cholesterol Homeostasis. Philippe Marmillot, Ph.D. Research Assistant Professor. Department of Biochemistry and Molecular Biology. 202-745-8000 ext 7661 (Office)

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Research Scientist Lipid Research Laboratory Veterans Health Administration Medical Center

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  1. Chronic Ethanol Consumption: Understanding The Mechanisms Of Ethanol-induced Hepatic Steatosis And Ethanol-induced Regulation Of Cholesterol Homeostasis Philippe Marmillot, Ph.D Research Assistant Professor Department of Biochemistry and Molecular Biology 202-745-8000 ext 7661 (Office) prcm@gwu.edu Research Scientist Lipid Research Laboratory Veterans Health Administration Medical Center Collaborations and Associates R. Lakshman PhD, R. Redman DDS PhD, M. Gong MD PhD, M. Garige MS, L. Castillo BS, O. Okojie BS Research Seminar Series November 8th, 2006

  2. Sub-Cellular Localizations of rab Proteins Plasma membrane rab 4 Post Golgi vesicles Trans Golgi network rab 6 Medial Golgi Cis Golgi Intermediate compartment rab 1 rab 2 Endoplasmic reticulum Objectives & Perspectives • In vivo (rats) and in vitro (HepG2 cells lines) studies • Co-immunoprecipitation studies rabs 1 & 2 with apoE & transferrin • IHC (confocal microscopy) studies of rabs 1 & 2 and apoE & transferrin • Postranslational studies, i.e., prenylation and glycosylation Alcohol & Liver Protein Trafficking:Role of G-Proteins Ethanol Treatment Decreases Rab2-ApoE Protein Interaction CONTROL HepG2 Cells apoE rab2 Financial Support NIH/NIAAA KO1 ETHANOL-Treated HepG2 Cells apoE rab2

  3. Objectives & Perspectives • Studies of overexpression (GFP) and silencing (siRNA) of annexins II and VI in relation with apoE or transferrin secretion. • Time-lapse microscopy study of protein trafficking in control and ethanol conditions. Role of Annexin(s) in Ethanol-Mediated Hepatomegaly Financial Support VA Medical Center Pilot grant Annexin VI is distributed in various subcellular compartments Apolipoprotein E associates with Annexin VI (co-immunoprecipitation)

  4. Objectives & Perspectives • Study of ethanol-induced regulation of receptors implicated in cholesterol transport. • Extend the study in human to correlate Ethanol consumption, HDL composition and defective RCT. Ethanol-Induced Change in HDL Composition and Reverse Cholesterol Transport (RCT) Financial Support NIH/NIAAA RO1 Reconstituted HDL system

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