Program Index

Online Application Form

Overview Transplant Pathology Environment Objectives and Core Competencies Activities and Duties Evaluation Overview The Division of Transplantation Pathology offers a one or two year fellowship program with the following mission: To train the fellow in interpretation of native and allograft liver, kidney, heart, and intestinal biopsies as well as resection specimens. To impart confidence in performing intra-operative surgical consultations (frozen sections). To teach the necessity of clinical-pathological correlations in arriving at meaningful surgical pathology diagnoses. To facilitate familiarity with modern molecular biology techniques that are revolutionizing laboratory medicine. To make the fellow familiar with data collection, statistical analysis, formal scientific presentation, and publication. To provide experience in teaching medical students and residents. For one-year fellowships the fellow will spend nine months in clinical service. The remaining three months are devoted to a research project. The second year of a two-year program will consist of six months of dedicated research and six months of clinical service. A research project suitable for publication in a peer-review journal is expected. The following description of ongoing research activities illustrates the variety of projects available for participation : Studies on the role of IL-6 in liver disease have shown that this cytokine is essential for maintaining biliary tree integrity and liver mass under conditions of biomedical stress, such as obstructive cholangiopathy. Using IL-6 deficient mice, a model of accelerated development and decompensation of biliary cirrhosis has been established. Analysis of IL-6/gp/30-dependent transcription factor activation is being used to determine how these signaling pathways contribute to the phenotype observed. Bile duct loss (ductopenia) is one of the major manifestations of chronic liver allograft rejection. Studies from our laboratories have shown that IL-6 and other inflammatory cytokines and growth factors contribute to biliary epithelial growth control. Moreover, baseline immunosuppressive drugs influence the production of cytokines by biliary epithelial cells. Studies are currently underway to determine how these baseline drugs influence ductopenia in liver allografts. This Division also maintains a robust clinical database, as a part of EDIT (Electronic Data Interface for Transplantation). This database links histology diagnoses and histologic findings with a multitude of clinical, serologic, matching, donor and outcome parameters. The database is an invaluable resource for clinical and patient-based research activities. A rat cardiac allograft model has shown the development of chronic obliterative arteriopathy and endocardial infiltrates in recipients pretreated with an infusion of allogeneic bone marrow cells. This chronic rejection is not seen in liver allograft recipients. Evidence has been obtained implicating lymphatic disruption as a pathogenic mechanism of chronic rejection. A computer algorithm has been developed (HLA matchmaker) that assesses donor-recipient HLA compatibility at the amino acid structural level. The algorithm makes intralocus and interlocus comparisons of amino acid triplets of HLA class I antigens. Transplant recipients of liver, kidney, heart or lung that receive donor BM at the time of solid organ transplantation are monitored for donor-specific alloresponses. These assays are carried out sequentially to determine whether enhanced donor chimerism can induce donor specific hypoalloreactivity. Studies are being conducted to characterize the host-pathogen interaction in normal and immunocompromised transplant recipients. Recurrent CMV infection in lung transplant recipients is a significant risk factor for the development of chronic lung rejection. Our research focusses on possible mechanisms that lead to chronic rejection in those patients. Lung transplantation is the only therapeutic option for many fatal lung diseases. The current immunosuppression protocols based on systemic cyclosporine or tacrolimus are not adequate to control rejection. A unique option is to target a high concentration of the immunosuppressive drugs to the lung allograft without increasing the systemic levels that might be toxic. Studies are bieng conducted in lung transplant patients that receive aerosol CsA on the role of various cytokines and effector molecules that can cause allograft damage and dysfunction. We also evaluate the impact of aerosol CsA on suppressing alloreactive T cells, on alloantibody formation and release of soluble donor derived HLA antigen. We are correlating the laboratory findings with the clinical parameters and determining whether these tests can be used as early markers of allograft damage. Based on in vitro and in vivo evaluation or cytokine production, it has been possible to characterize individuals as "high" or "low" producers for a given cytokine. Such polymorphisms correspond to allelic variation that can be determined by DNA genotyping. We are interested to study what the relationship is between cytokine polymorphism and clinical outcome after organ transplantation. High producers of proinflammatory cytokines such as TNF- may develop more acute rejection and require augmented immunosuppression. In contrast, patient with low TNF- and high IL-10 genotype (a suppressive cytokine) may experience less rejection. Cytokine polymorphisms may also influence other post-transplantation outcomes such as infections and allergic side effects of immunosuppressive agents. The clinical profile of patients with BK virus infection in the renal allograft has been defined. DNA sequencing of viral strains has revealed a variety of mutations, which may be relevant to the pathogenesis of an extremely refractory interstitial nephritis seen in these individuals. The interplay between host and viral immune factors in this disease is being investigated in an in-vitro culture model. Studies on human hepatocytes have shown that IL-6 and HGF regulate the activity of cytosolic phospholipase A2 (cPLA2) in cultured human hepatocytes. The regulation of cPLA2 by cytokines and growth factors may play a role in the pathophysiology of inflammatory and non-inflammatory liver diseases. Parmjeet S. Randhawa, MD Director, Transplant Pathology Fellowship Program Room E-737 Montefiore University Hospital 200 Lothrop Street Pittsburgh, PA 15213 Office Phone: (412) 647-7646 Fax: (412) 647-5237 E-mail: randhawapa@upmc.edu