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 systemic lupus is a major focus of the laboratory research. Developing therapeutic strategies for clinical organ transplantation and lupus in humans 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) Mechanisms of autoimmunity in systemic lupus: Many autoimmune diseases represent a breakdown of immune tolerance to self-antigens. The mechanisms by which 1) animals develop tolerance to self during ontogeny, 2) tolerance is broken in adult life resulting in systemic autoimmune diseases such as lupus, and 3) tolerance can be reestablished after the development of autoimmune disease are the subjects of investigation. Our laboratory is involved in identifying those cells (NKTcells, Treg cells, myeloid derived suppressor 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 these cells are important suppressors of tumor immunity as well as autoimmunity, and genetic abnormalities in these cells can promote systemic lupus