Physician Investigator (Cl) Pathology, Mass General Research Institute

Associate Professor of Pathology Harvard Medical School

Pathologist Pathology, Massachusetts General Hospital

MD Case Western Reserve University School of Medicine 1992

PhD Case Western Reserve University School of Medicine 1977

antibody-mediated rejection; cellular rejection; graft rejection; graft survival; heart grafts; isoantibodies; kidney grafts; kidney transplantation; pancreatic islet grafts; transplantation pathology

Dr. Smith’s research focuses primarily on the immunology of transplantation, with emphasis on the transplantation pathology of the heart, kidney, and pancreatic islets. He is particularly interested in how the acute and chronic rejection of allografts and xenografts come about.

Studies involve patients and animal experimentation with heart, kidney and pancreatic islet grafts. With expertise in these areas, Dr. Smith is a consultant pathologist to investigators within Harvard community, national consortia, and the Transplant Biology Research Program at MGH with clinical and preclinical transplant programs. Dr. Smith is also a consultant to revisions of the classification scheme for human heart allograft biopsies.

Current emphasis and ongoing work includes studies of cellular and humoral rejection in cardiac allografts of humans and mice (hearts) and in kidneys of monkeys and humans. Dr. Smith has been able to correlate by indirect immunofluorescence C4d staining and the presence of alloantibodies in cardiac allografts.

With investigators at other institutions, using clinical data, criteria are being established for the diagnosis of acute antibody-mediated rejection in human cardiac transplants. Dr. Smith and Dr. Colvin are studying the progression of monkey kidney allograft rejection that comes about with development of alloantibodies, chronic antibody-mediated rejection.

They have been able to establish that alloantibodies are the causative of the glomerulopathy of chronic humoral rejection in allografted kidneys, and established that chronic antibody-mediated rejection develops through four stages. Dr. Smith, along with other investigators studying islet allograft survival, has established that portal vein-based islet allografts can undergo a non-immunological senescence.

Dr. R. Abdi and Dr. Smith are investigating why knockout of certain chemokine genes, dendritic cells, and stem cells affect graft rejection and donor dendritic cell migration. In some autologous stem cell transplants in mice, sarcomas developed. With AB Collins and Dr. JR Stone we have established the utility of immunofluorescence for the classification of amyloid deposits. With Dr. M. Soares investigations are ongoing into the mechanism of cerebral malaria. New work with Dr. E. Zorn and J Fraser seeks to identify new alloantibodies in graft rejection by novel proteomic approaches.