Shu Man Fu
Primary AppointmentMargaret M. Trolinger Professor of Rheumatology, Medicine: Rheumatology and Immunology
- PhD, Rheumatology & Immunology, Stanford University
- MD, Stanford Medical School
Human lymphocyte biology and autoimmunity
The laboratory is focused on identification of the genes involved in the pathogenesis of SLE. In addition, autoantigens which are the target for nephritis in NZM2328.C57L/J.c4 are to be identified. Separate loci for acute and chronic glomerulonephritis (GN) were identified on the distal portion of chromosome 1. The genetic data were confirmed by the phenotypes of a congenic strain (NZM238.C574Jc1). Further mapping by the generation of intrachromosomal recombinant strains of the C1 congenic resulted in an informative strain NZM2328.R27, showing that acute GN need not progress to chronic GN and that acute GN and chronic GN are under separate genetic control.
Current efforts are to elucidate the genes controlling these phenotypes. In addition, the hypothesis that molecular mimicry initiates the initial autoimmune response, which diversifies to multiple autoantigen, resulting in end organ damage in suitable hosts is being tested. The role of MHC in this process in both mice and men is being investigated. In this regard, bacterial and viral agents sharing cross reactive T and B cell epitopes with human auto antigens are logical candidates for molecular mimics in this process.
In collaboration, the laboratory is interested in the mechanisms of autoantibody diversification and the role of T cells in the pathogenesis of glomerulonephritis. Recently we have focused our attention on the role of molecular mimicry to environmental antigens at the T cell level in the generation of lupus related autoantibodies. Our laboratory findings let us put forward a new hypothesis on the pathogenesis of SLE.