Overview

The objectives of my laboratory are to apply the fundamental concepts and broad technologies of cell/molecular biology to understand hepatic epithelial cell function and dysfunction. Our focus is principally on cholangiocytes (epithelial cells that line intrahepatic bile ducts) because of their biologic and clinical importance, the new hypotheses and techniques we have developed for their study, and the role we have played in advancing cholangiocyte pathobiology, an underserved area of research. Currently, my lab has two major parallel programs focused on cholangiocyte pathobiology each supported by an RO1 grant from NIH.

First, we investigate cholangiocyte water and solute transport by testing the central hypothesis that cholangiocyte bile production is the net result of solute-driven, bidirectional passive movement of water molecules through water selective channels (aquaporins) constituitively expressed on or recycled among cholangiocyte cellular compartments. We utilize new models including: aquaporin knock-out mice; cultured rat cholangiocytes transfected with AQP-green fluorescent fusion constructs; immunoisolation of AQP-1 containing transport vesicles; intact closed or perfused rat bile duct units; subpopulations of rat cholangiocytes isolated from different bile duct segments; and computer-generated three-dimensional reconstruction of the rat biliary tree.

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