Harvard Catalyst Profiles

This laboratory has focused on the molecular pathogenesis of infections in immunocompromised hosts. We have isolated and cloned the major surface antigens of the fungal pathogen Pneumocystis carinii. We have studied pathogenesis of infections by the porcine endogenous retrovirus and other porcine viruses to prevent infection in future pig-to-human xenotransplantation, as a model for organ-donor-derived infections. The virus (PERV) has been cloned and quantitative assays developed for this potential pathogen. This approach has been used nationally and internationally in the development of guidelines for screening of organ donors in solid organ transplantation and xenotransplantation including the FDA Advisory Panel on Xenotransplantation, guidelines for Harvard Medical School, US Public Health Service, Health Canada, Institute of Medicine, and World Health Organization.
Clinical investigation has been an outgrowth of the Transplant Infectious Disease Program. Trials of innovative therapies for Pneumocystis infection (atovaquone) in stem cell and solid organ transplantation and of bioavailability of new antiviral agents (ganciclovir) grew directly out of clinical need for such therapies. More recently, we have developed clinical protocols for the national multicenter Clinical Trials in Organ Transplantation to monitor viral infections using novel mutiplexed viral molecular assays, approaches to antimicrobial prophylaxis (ganciclovir, valganciclovir) and therapy (posaconazole) in immunosuppressed hosts, for the harmonization of laboratory assays for viral infections across multiple assay platforms at multiple clinical centers, and for antibody responses to vaccination following heart and kidney transplantation. We have also participated in animal and human trails of the induction of immune tolerance for organ transplantation.