Our lab studies the epithelial response to wounding, focusing on the liver as a paradigm for most epithelia. Chronic liver disease involves deposition of extracellular matrix that guides the repair process but, when extensive, also disrupts the structure and ultimately the function of the tissue. Our lab has studied the fibrogenic response to liver injury, defining the role of a pericyte population (known in the liver as stellate cells) in this process. Another important component of the injury response is cell replacement and tissue remodeling. Recent work indicates that cell replacement occurs not only by division of mature hepatocytes but also through expansion of a progenitor cell compartment. In recent work, we have begun to define the role of progenitors known as "oval cells" in the repair response. Oval cells can be isolated and, with expansion in culture, could be useful for cell-based therapy of a variety of liver diseases. We and our collaborators have recently defined a member of the TNF a family of cytokines that appears to be a specific growth factor for a subset of hepatic oval cells. Currently we are characterizing the cells that respond to this factor. Another project is concerned with the interaction between advanced liver injury (fibrosis or cirrhosis) and initiation of primary liver cancer. A striking and prevalent example of this association is chronic hepatitis C, in which cancer arises almost exclusively in the setting of cirrhosis. For these studies we have developed a transgenic mouse with conditional (tetracycline-regulated) expression of the hepatitis C virus core gene. This allows us to manipulate the context of hepatocarcinogenesis independent of the initiating viral product, towards identifying those facets of the injury response that are required for tumor formation. |
Chang ML, Chen JC, Alonso CR, Kornblihtt AR, Bissell DM. Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver. Proc Natl Acad Sci USA 2004;101:18093-98.
Kikuchi S, Griffin CT, Wang SS, Bissell DM. Role of cd44 in epithelial wound repair: migration of rat hepatic stellate cells utilizes hyaluronic acid and cd44v6. J Biol Chem 2005;280:15398-404.
Jakubowski A, Ambrose C, Parr M, Lincecum JM, Wang MZ, Zheng TS, Browning B, Michaelson JS, Baetscher M, Wang B, Bissell DM, Burkly LC. Tweak induces liver progenitor cell proliferation. J Clin Invest 2005;115:2330-40.
information last updated July 2006 |
Biomedical Sciences (BMS) Graduate Program
