Dr. Wooley's research interests include the immunogenetic regulation of autoimmune diseases (particularly rheumatoid arthritis), the immune response to biomaterials, and gene therapy for the treatment of connective tissue disorders. His laboratory is currently engaged in studying immunoregulation of murine models of arthritis (type II collagen-induced arthritis, pristane-induced arthritis, proteoglycan-induced arthritis, and MRL disease), examining the role of vitamin D receptor and type I collagen genes in bone density, and elucidating the role of the immune response in the pathology of aseptic loosening of joint prostheses. These projects are investigating the genetic regulation of arthritis susceptibility, with an emphasis on the role of the Class II antigen genes, T cell receptor genes, and Mls genes. Immunotherapeutic and gene therapy approaches to the treatment of the rheumatic diseases are being studied using the murine models of arthritis and inflammation. Using immunotherapy with cytokine antagonists and gene therapy with retroviral vectors encoding anti-inflammatory cytokines, strategies are being developed to modulate the autoimmune response to connective tissue components, particularly type II collagen and high density proteoglycans, the abnormalities in autoimmune T cell populations, and the inflammatory response to implanted biomaterials. Murine models are also being used to examine the influence of polymers, including silicones and polyethylenes, on the immune response, particularly during autoimmune reactions to connective tissue antigens. The role of the biological response to implanted biomaterials is also under investigation, using the murine air pouch model to investigate the biological response using histological, immunological, and molecular techniques. Funding for these various projects is provided by the NIH, the Arthritis Foundation, the Department of Defense, and the Veterans Administration.