• D. Phil, University of Oxford, 1990
• M.D., Emory University School of Medicine, 1984
• B.A., Emory College, 1980

Websites: http://transplant.emory.edu
http://www.surgery.emory.edu

Research Interests: Solid organ transplantation is now a routine treatment for end-stage organ failure. Though current medications that suppress the immune system are effective in limiting episodes and severity of acute transplant rejection, life-long therapy is required. In addition immunosuppressive therapy is associated with increased risks of infections and cancer and there are numerous unwanted side effects. One strategy that has recently emerged as a possible alternative to conventional immunosuppressive therapy is the specific targeting of the key pathways that lead to T cell activation (Œ"costimulatory pathways"), the main cell involved in organ rejection. Using this strategy we have developed a hematopoietic chimerism (recipient and donor-derived blood cells co-existing in the recipient) protocol in which a safe, non-myelosuppressive dose of a chemotherapeutic agent is combined with CD40/CD28 costimulation blockade and an infusion of donor bone marrow cells result in the development of robust donor-specific tolerance in adult animals. Ongoing studies are aimed at identifying the pathways and understanding cellular and molecular mechanisms responsible for tolerance to allografts in rodent and nonhuman primate models. Translation of these approaches into successful tolerance regimens in human clinical trials is currently underway for achieving transplantation tolerance (organ acceptance in the absence of immunosuppression) and long-term survival of allografts. Specific projects include:

I. Rodents

• a) Protective immunity and transplantation tolerance: develop experimental models to study the interactions of viral infections, protective immunity and tolerance
• b) Donor-specific T cell memory: experimental models to study the phenotype, activation and survival requirements of allospecific memory T cells.

II. Nonhuman primates

• a) Test strategies using costimulation blockade in combination with donor-specific transfusion in islet cell and renal allograft models in rhesus macaques.
• b) Explore strategies utilizing costimulation blockade combined with non-myeloablative conditioning and bone marrow transplantation to induce stable long-term hematopoietic chimerism and transplantion tolerance to renal allografts in the rhesus macaques.