R. Brian Doctor, Ph.D. (PI)
Kelley Brodsky, M.S.
Our laboratory seeks to understand the physiology and pathophysiology of the epithelial cells that line the intrahepatic bile duct. These cells, termed cholangiocytes, have a potent secretory-absorptive capacity that enables the epithelium to contribute significantly to the physiologic formation of bile. The focus of the Physiology Section of the laboratory is to understand the role of cytoskeletal linking proteins in sequestering specific transport and regulatory proteins within membrane microdomains and moderating the transepithelial fluxes of ions, solutes and water across the epithelium. As an example, our laboratory discovered an epithelial cell-specific form of Shank2E. This protein links a number of specific transport proteins to the actin cytoskeleton underlying the apical, microvillar membrane. More recent studies suggest that Shank2E is a central protein in the regulated recovery of these proteins from the microvillar membrane.
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‘Apical TIRF’ refines live cell imaging of the apical domain of OK cells. |
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The bile duct is site of genesis for a number of liver diseases, including cystic diseases of the liver. The Pathophysiology Section of our laboratory currently investigates the mechanisms that underlie the growth of liver cysts. These findings will direct the development of medical therapies to intercede in growth and pathology associated with liver cysts. An area of interest is the role of cytokines and growth factors play in driving liver cyst growth. For example, our recent studies have demonstrated that in vivo inhibition of VEGF signaling markedly diminishes the growth of liver cysts during the lifetime of the animal.
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Inhibition of VEGF signaling blocks liver cyst growth. |
