Research
The laboratory is engaged in investigations into organ transplant immunology – understanding the mechanisms by which allogeneic grafts are rejected or accepted, translating this knowledge to the clinic, and exploring a method of inducing organ transplant tolerance.
There are three major areas of research in the laboratory. First, we are investigating the mechanisms of hepatic tolerance. Utilizing mouse orthotopic liver and heterotopic heart transplantation models, the role of CD25+ CD4+ regulatory T cells (Treg) is being delineated. Our recent studies have implied an obligatory role for CD25+ CD4+ Treg in liver spontaneous tolerance; therefore we are studying which factor participates in the induction and expansion of Treg, including liver dendritic cell and NKT cells. Second, we are analyzing the costimulatory signals, in particular the negative regulatory role of the B7: CTLA4 and PD-L: PD-1 pathway in controlling T and NKT cell responses using transgenic approaches and organ transplant models. Our studies suggest that blockade of the interaction of B7: CTLA4 or PD-1: PD-L1 signaling enhances anti-donor immunity, reverses spontaneous liver tolerance, and accelerates heart allograft rejection. Third, we are exploring the therapeutic approaches of gene vector and stem cell based therapy in organ transplant recipients.
