Current Research and Scholarly Interests
Our interests are in the area of cellular immunology, and the regulatory interactions between subpopulations of immune cells. In particular, we are interested in the identification, function, and molecular mechanisms by which some subpopulations of lymphocytes amplify the immune response and some such as natural killer T cells (NKT cells) and regulatory T cells (Treg cells) suppress it. Investigation into interactions of the cells during the immune response to organ and bone marrow transplants and in tumor immunity is a major focus of the laboratory research. Developing therapeutic strategies for clinical organ transplantation in humans with hematologic or solid tumors based on these principles is a major goal. Specific areas of research are as follows:
(i) Immune tolerance to organ and bone marrow transplants: Immune tolerance is recognized to be the paralysis of the immune system in its response to a given antigen, the development of anergy, or antigen-specific suppressor cells. Our research programs are studying these mechanisms at the cellular and molecular levels in laboratory animals and humans that are made tolerant to foreign organ or bone marrow transplants. In the case of bone marrow transplants, the goal is to prevent graft vs. host disease while maintaining graft anti-tumor activity.
(ii) In the case of organ transplants, the goal is to achieve acceptance of the transplants in the absence of maintenance immonosuppressive drugs. Tolerance is achieved by establishment of mixed chimerism. Our mouse models have been translated to clinical studies in which tolerance and prevention of graft vs host disease have been achieved. Our laboratory is involved in identifying those cells (NKTcells, Treg cells, myeloid derived suppressor cells, dendritic cells) involved in the induction and maintenance of immune tolerance with regard to their surface receptors, effector functions, and the nature of secreted molecules which mediate their function. We have shown that interactions of these cells are important suppressors of tumor immunity and promoters of organ transplantation tolerance.
(iii) In the case of hematologic and solid tumors, the goal is to eliminate cells that mediate immune tolerance in the tumor microenvironment such that effector T cells can kill the tumor cells. Target cells for depletion include myeloid derived suppressor cells, Treg cells, and tolerogenic dendritic cells.