Shu Man Fu, PhD Lab
Professor, Medicine: Rheumatology and Immunology
Center for Immunity, Inflammation, and Regenerative Medicine
PO Box 800133
Charlottesville, VA 22908
EDUCATION AND TRAINING
- PhD, Immunology, Rockefeller University, New York, NY
- MD, Stanford Medical School
- Residency, Internal Medicine, Stanford University
Human lymphocyte biology and autoimmunity
Autoimmunity is essential in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The emphasis of my laboratory is on the genetic and environmental factors necessary for these disorders. We have been focused on the mouse model NZM2328 for SLE. This model was characterized by our laboratory and was used to identify genetic loci for susceptibility to SLE. A locus controlling nephritis and anti-dsDNA antibody production was determined. The disassociation of ANA and lupus nephritis was demonstrated in a congenic strain (NZM2328.C57L/J.c4).
The laboratory focuses on identifying 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.
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 autoantigens, 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. 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.