Lab Research Focus
My major research interests are: 1) immunoglobulin gene expression in synovial tissue of patients with rheumatoid arthritis (RA), 2) the genetics of rheumatoid arthritis and the influence of genetic variations on disease severity and response to treatment, and 3) the role of B lymphocytes in liver of patients with chronic hepatitis C.
My laboratory is using micromanipulation and single cell PCR to analyze clonality of B and T cells in RA synovium and will use in vitro expression to analyze the antigenic specificity of recombinant antibodies containing clonally-expanded VH and VL domains. We are involved in analyzing the role of genetic variations in TNF, lymphotoxin, and TNF receptors in the clinical response to the first FDA-approved biologic agent for the treatment of RA, a TNFreceptor:Fc fusion protein, etanercept (Enbrel). In addition, we have identified a novel single nucleotide polymorphism and 5 haplotypes in the 5' region of the IL-6 gene which vary in their prevalence among different races and may influence susceptibility to RA or its clinical manifestations. We are involved in a nation-wide study of families with RA, to identify non-MHC genes important in the pathogenesis of RA. Finally, we are beginning a project to determine the role of periportal lymphoid follicles in cryoglobulinemia in patients with chronic hepatitis C infection, again using micromanipulation/single cell PCR and expression of recombinant antibodies.
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