Sheri Krams

Research/Lab website:   Personal Web site

Recent evidence suggest the importance of the innate immune system in both graft rejection and the induction of tolerance after solid organ transplantation. We have determined, utilizing a high-responder model of rat allogeneic liver transplantation, that NK cells of host origin infiltrate grafts soon after transplantation leading us to hypothesize that activation of NK cells is important in the early events after transplantation. However, relatively little is understood about NK cell activation in the context of transplantation. We have recently cloned a novel NK cell receptor directly from the infiltrating lymphocytes of a rat liver allograft. Sequence analysis indicates this receptor (rNKp30) has homology to the human NK cell activation receptor NKp30.
We will characterize the novel receptor rNKp30 and explore its potential in the activation of NK cells in the context of transplantation. Knowledge of NK cell activation receptors, ligands, and effector pathways will advance our understanding of NK cell biology and clarify the role of the innate immune system in solid organ transplantation. In related experiments the specific effects of immunosuppressive drugs on NK cells are being explored.

Current research focuses on apoptosis and apoptosis related proteins. Our data suggest that apoptosis has a dual role in transplantation, a deleterious role as a mechanism of graft cell damage and a benefical one involving elimination of alloreactive cells. Studies are underway to explore the mitochondria-mediated events initiated by the activation of proapoptotic molecules such as Bid and Bax in hepatocyte apoptosis seen during graft rejection and liver disease.

We are also utilizing microarray technology to examine specific genes which may be important in the pathogenesis of human liver disease. The objective of these studies is to elucidate the immune mediated events which may lead to lymphocyte accumulation and injury to the liver in patients with the neonatal liver disease biliary atresia and the autoimmune disease primary biliary cirrhosis.