Distinguished Professor of Surgery and Pathology and Laboratory Medicine, Vice-Chairman, Basic Science Research in the Department of Surgery; and Director of the Dumont-UCLA Transplantation Research Laboratories in the Division of Liver and Pancreas Transplantation. David Geffen School of Medicine at UCLA

Ischemia-reperfusion injury (IRI), inflammation/tissue damage response, is a major obstacle limiting the success of liver transplantation in patients with end-stage liver disease and those with tumors of hepatic origin. Dr. Kupiec-Weglinski hypothesizes that liver IRI results from impaired regulation between innate (e.g., macrophage-dependent) and adaptive (T cell-driven) immune mechanisms. He is pursuing multiple novel approaches for combating liver damage induced by IRI, as necrosis of hepatocytes releases mediators that initiate and amplify the inflammatory process that ultimately lead to graft rejection. One of the approaches consists in locally inducing heme oxygenase-1 (HO-1) that protects against the severity of cellular oxidative stress. Indeed, recent studies substantiate the clinical relevance of HO-1 cytoprotection and identifies SIRT1-mediated autophagy pathway as a new essential regulator of HO-1 function in IR-stressed orthotopic liver transplantation. Dr. Kupiec-Weglinski has also shown the role of innate immunity in liver IRI. He is exploring the hypothesis that cross talk between the opposing pathways, i.e., HO-1 in the donor organ, and TLR4 in the recipients is instrumental in the mechanism of liver IRI. An additional hypothesis is that Nrf2 controls dysregulated HO-1-TLR4 signaling during IRI. A new and surprising finding is the identification of a role of the gut microbiome in the severity of IRI. An understanding of these intracellular signal transduction pathways and intercellular communications is of critical importance for designing safe and effective therapeutic strategies to ameliorate liver ischemia-reperfusion injury in patients. Dr. Kupiec-Wiglinski will serve as one of the leaders of Program A.

jkupiec@mednet.ucla.edu
310-825-4196

US MAILING ADDRESS:
Jerzy Kupiec
UCLA Surg-Liver & Pancreas Transplantation
BOX 957054, 2780 MRL
Los Angeles, CA 90095-7054