Physician Investigator (Cl) Infectious Disease, Mass General Research Institute

Professor of Medicine Harvard Medical School

cytomegalovirus; cytomegalovirus infections; endogenous retroviruses; infection; infections of the immunocompromised host; nk cell activity; organ transplantation; pig-to-primate xenotransplantation; post-transplant lymphoproliferative disorders; tissue donors; transplantation; transplantation heterologous; viral infection in transplantation; xenotransplantation; zoonoses

Dr. Fishman's research is focused on the pathogenesis of infections in immunocompromised hosts including:

• Studies of the molecular biology of viruses associated with pig-to-primate xenotransplantation including porcine endogenous retrovirus, porcine lymphotropic herpesvirus, porcine cytomegalovirus
• Large animal models of post-transplant lymphoproliferative disorders
• Indirect effects of viral infection in solid organ and stem cell transplantation

Xenotransplantation: Studies of infection associated with interspecies transplantation have resulted in the identification of a variety of potential pathogens in pig-to-primate transplantation. This laboratory has achieved the first cloning and full-length sequencing of endogenous retroviruses from swine (PERV). A recombinant form of PERV (A-C) has been identified that is infectious for human cells in vitro. The mechanisms underlying this recombination and infectivity for human cells are under investigation.

Viral Infection in transplantation: Chronic allograft vasculopathy (CAV) of the coronary vasculature is a major cause of death in cardiac transplant patients. In murine heart transplantation, both T-cells and NK cells are involved in the pathogenesis of cardiac graft vaculopathy. We have demonstrated that Lymphocytic Choriomeningitis Virus (LCMV) induces CAV in T-cell deficient mice. We have isolated NK cell activity using RAG1-/- mice, which are deficient in T and B cells, but have an intact NK cell population. LCMV induced CAV in parental to F1 cardiac transplants in RAG1-/-mice.

Clinical Investigation: An active program in clinical investigation is in collaboration with the Transplantation and the Hematopoietic and Stem Cell Transplant Units. Studies of the pathogenesis of viral infections, the role of cytomegalovirus, novel viral vaccines, and of prophylaxis for bacterial, viral, and fungal infections in the immunocompromised host are ongoing.