Major Research Interests: Transplantation Immunology and Tolerance Induction, Bone Marrow Chimerism, Hematopoietic Stem Cell Biology, Innate and Adaptive Immunity, and Lung Cancer.
Less than half of all lung transplant patients survive more than 5 years as a result of opportunistic infections, chronic rejection, end-organ toxicity or secondary malignancy. Therefore, our major research efforts are focused on approaches to re-educate the recipient immune system for the induction of permanent donor-specific tolerance while maintaining recipient immunocompetence. Engraftment of both donor and recipient hematopoietic stem cells (SC) results in mixed bone marrow (BM) chimerism, induces donor-specific tolerance for allogeneic and xenogeneic solid organ grafts, preserves recipient immunocompetence, and is not associated with chronic rejection. However, the morbidity and mortality associated with graft vs. host disease (GVHD), ablative recipient conditioning, and failure of SC engraftment has prevented the direct clinical application of BM-induced tolerance. We have characterized a rare BM-derived cell population known as the facilitating cell (FC), that is sufficient to permit engraftment of highly purified murine SC in completely MHC-disparate recipients and induce transplantation tolerance without evidence of GVHD. Our laboratory has identified a novel member of the T cell receptor beta (TCRbeta) heterodimer family on the FC, that is responsible for the unique properties of allogeneic SC facilitation and tolerance induction in vivo. Isolation, purification, and characterization of the FCp33/TCRbeta/CD3epsilon receptor and the signaling pathways utilized for tolerance induction form a major research focus of the current NIH funded laboratory.
Other active research interests are involved in the study of the role of innate immunity in chronic rejection of human lung allografts and local therapies for the treatment of lung cancer.