18. GOALS FOR FELLOWSHIP TRAINING AND CAREER My goals for the fellowship training is to develop as an immunologist: to become adept at formulating interesting and fruitful research questions relating to immuno- logy and apoptosis, to hone my experimental techniques, and to acquire the ability to provide accurate and critical analysis of available !data. Working and training with Dr. Krams will provide ample opportunity to gain these skills and many other yet unforeseen skills as a scientist. This fellowship training will help me to plan my exact career plans in immunological research and will provide a specific research area in which to focus. SPONSOR 19. NAME AND DEGREE(S) Sheri M. Krams, Ph.D. 20. POSITION/RANK Assistant Professor 21. RESEARCH INTERESTS/AREAS Effector cell function in response to alloantigen and autoantigen, apoptosis, tolerance. RESEARCH PROPOSAL 22. DESCRIPTION (Do notexceed space provided) Our laboratory and others have observed apoptosis of infiltratirigslymphocytessirir. some animal models of long term allograft survival. Furthermore, we have identified apoptotic lymphocytes in the immediate post-transplant period in biopsies of human liver allografts. Taken together these studies raise the intriguing possibility that under certain conditions, graft infiltrating cells could undergo apoptosis thus effectively eliminating alloreactive cells. In this research proposal we will examine the means by which immunoregulatory cells can induce apoptotic cell death of infiltrating cells resulting in long-term graft survival. We will define the con- ditions that determine and regulate the apoptosis of infiltrating cells, and to-n understand the role of the Fas/FasL pathway in deletion of these cells. We will utilize two experimental models, a model in which tolerance is induced by treatment with anti-CD4 monoclonal antibodies and a model in which there is spontaneous allo- graft tolerance. Recent studies have indicated that some immunosuppressive drugs actually interfere with the induction of tolerance. We will systematically examine the influence of CSA, FK506, and Rapamycin on apoptosis of peripheral and graft in- filfrat-ing 1 ympTinryf-ps in the setting of transplantation. PHS416-1 (Rev. 12/98) Form Page 2 BB cc Individual NRSAApplicaff NAME ^flrs1'mlddle''* Table of Contents ========================================Section End===========================================
