Anthony J. Demetris, Professor
Director, Division of Transplant Pathology
MD, University of Pittsburgh, 1982
Email: demetr@a1.isd.upmc.edu
There are two principle areas of active NIH-funded investigation in Dr. Demetris's laboratory: 1) the role of inflammatory cytokines and growth factors in the development of cirrhosis; 2) tolerance induction and chronic tissue rejection. Each of these areas includes a spectrum of projects ranging from basic research involving cell and molecular biology, to experimental animal models, and finally, clinical applications.
The areas of inflammation cytokines and growth factors in the development of cirrhosis focus on the role of interleukin-6 in the development of biliary type cirrhosis, and the contribution of interleukin-6/gpl30 and HGF/met signaling in the compensation pattern of cirrhosis. Our recent studies show that interleukin-6 knock-out mice develop bilary cirrhosis at an accelerated pace and decompensate more quickly than wild-type animals. This can be reversed with exogenous IL-6. Projects include molecular biologic mecha-nisms of biliary epithelial cell growth control via IL-6/gp130 signaling, the use of IL-6 knock-out mice to examine the development of cirrhosis, and clinical trials of growth factors and cytokines to treat patients with end-stage liver disease.
The area of tolerance induction and chronic rejection includes using a small animal model of chronic cardiac allograft rejection. This research project also spans the spectrum from basic research into the role of intracellular cytokines, to manipulations of the experimental animal model, to clini-cal studies involving bone marrow augmentation of solid organ allograft recipients.
Recent Publication
Demetris AJ, Murase N, Starzl, Fung JJ: Pathology of chronic rejection: an overview of common findings and observations about pathogenic mechanisms and possible prevention. Graft I(2), Suppl II: 52-59, 1998.
Liu Z, Sakamoto T, Ezure T, Yokomuro S, Murase N, Michalopoulos G, Demetris AJ: Interleukin-6, hepatocyte growth factor, and their receptors in biliary epithelial cells during a type I ductular reaction in mice: interactions between the periductal inflammatory and stromal cells and the biliary epithelium. Hepatology 28(5): 1260-1268, 1998.
Sakamoto T, Liu Z, Murase N, Ezure T, Yokomuro S, Poli V, Demetris, AJ: Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy. Hepatology 29(2): 403-411, 1999.
Duquesnoy RJ, Liu K, Fu XF, Murase N, Ye Q, Demetris AJ: Evidence for heat shock protein immunity in a rat cardiac allograft model of chronic rejection. Transplantation 67(1): 156-164, 1999.
