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Philippe Marmillot, Ph.DResearch Assistant Professor
Research Seminar Series November 8th, 2006
Department of Biochemistry and Molecular Biology
Chronic Ethanol Consumption:Understanding The Mechanisms Of Ethanol-induced Hepatic Steatosis
AndEthanol-induced Regulation Of Cholesterol Homeostasis
Research ScientistLipid 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
202-745-8000 ext 7661 (Office)[email protected]
Alcohol & Liver Protein Trafficking:Role of G-Proteins
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
CONTROL HepG2 Cells
ETHANOL-Treated HepG2 Cells
apoErab2
apoErab2
Financial SupportNIH/NIAAA KO1
rab 2
rab 4
rab 6
rab 1
Plasmamembrane
Post Golgivesicles
Trans Golginetwork
Medial Golgi
Cis Golgi
Intermediatecompartment
Endoplasmicreticulum
Sub-Cellular Localizations of rab Proteins
Ethanol Treatment Decreases Rab2-ApoE Protein Interaction
Annexin VI is distributedin various subcellular compartments
Apolipoprotein E associateswith Annexin VI (co-immunoprecipitation)
Role of Annexin(s) in Ethanol-Mediated
Hepatomegaly
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.
Financial SupportVA Medical Center
Pilot grant
Ethanol-Induced Change in HDL
Composition and Reverse Cholesterol
Transport (RCT)Reconstituted HDL system
Financial SupportNIH/NIAAA RO1
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.
