Arthritis Pathogenesis: Development of Novel Diagnostic and Therapeutic Approaches
We investigate the pathogenesis of rheumatoid arthritis and osteoarthritis to develop new diagnostic tools and therapies.
The scientific approach includes clinical studies in collaboration with the Divisions of Rheumatology and Orthopedic Surgery at Scripps Clinic, laboratory research on human patient tissues, animal models, cell and molecular biology.
The rheumatoid arthritis research program addresses mechanisms involved in the activation and proliferation of synovial fibroblasts and of mononuclear phagocytes. Gene expression analysis of peripheral blood leukocytes from rheumatoid arthritis patients is used to identify new mediators of the aberrant inflammatory response and predictors of the patients' response to antirheumatic therapy. Intracellular signaling pathways in monocytes and synovial fibroblasts are studied for the identification of novel targets for antirheumatic therapy.
The osteoarthritis research program is focused on mechanisms of joint aging. A multidisciplinary program project analyzes cellular, biochemical and molecular changes that occur in joint aging and represent risk factors for the development of osteoarthritis. Gene expression analysis will document the complete spectrum of genes, termed chondrome, that are expressed by chondrocytes at defined stages of activation and differentiation and in normal aging and osteoarthritic tissues. Several programs are evaluating novel therapeutic approaches in animal models of the disease. Lead candidates that target novel mediators are being prepared for clinical trials. A clinical project on patients with joint trauma who are at risk for early development of osteoarthritis defines sensitive markers to monitor disease progression and efficacy of new therapeutic interventions.