Shu Man Fu, PhD Lab
Professor, Medicine: Rheumatology and Immunology
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 plays an important role in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The emphasis of my laboratory is on the genetic and environmental factors important 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 of SLE. A locus controlling nephritis and anti-dsDNA antibody production was identified. The disassociation of ANA and lupus nephritis was demonstrated in a congenic strain (NZM2328.C57L/J.c4).
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.
- Dai C, Wang H, Sung SS, Sharma R, Kannapell C, Han W, Wang Q, Davidson A, Gaskin F, Fu SM, Interferon alpha on NZM2328.Lc1R27: enhancing autoimmunity and immune complex-mediated glomerulonephritis without end stage renal failure., 2014; Clinical immunology (Orlando, Fla.). 154(1) 66-71. PMID: 24981059 | PMCID: PMC4167638
- Ge Y, Jiang C, Sung SS, Bagavant H, Dai C, Wang H, Kannapell CC, Cathro HP, Gaskin F, Fu SM, Cgnz1 allele confers kidney resistance to damage preventing progression of immune complex-mediated acute lupus glomerulonephritis., 2013; The Journal of experimental medicine. 210(11) 2387-401. PMID: 24101379 | PMCID: PMC3804943
- Ge Y, Brown MG, Wang H, Fu SM, Genetic approach to study lupus glomerulonephritis., 2012; Methods in molecular biology (Clifton, N.J.). 900() 271-90. PMID: 22933074 | PMCID: PMC3873643
- Sharma R, Fu SM, Ju ST, IL-2: a two-faced master regulator of autoimmunity., 2011; Journal of autoimmunity. 36(2) 91-7. PMID: 21282039 | PMCID: PMC3046218
- Sharma R, Sharma PR, Kim YC, Leitinger N, Lee JK, Fu SM, Ju ST, IL-2-controlled expression of multiple T cell trafficking genes and Th2 cytokines in the regulatory T cell-deficient scurfy mice: implication to multiorgan inflammation and control of skin and lung inflammation., 2010; Journal of immunology (Baltimore, Md. : 1950). 186(2) 1268-78. PMID: 21169543 | PMCID: PMC3136806
- Sharma R, Deshmukh US, Zheng L, Fu SM, Ju ST, X-linked Foxp3 (Scurfy) mutation dominantly inhibits submandibular gland development and inflammation respectively through adaptive and innate immune mechanisms., 2009; Journal of immunology (Baltimore, Md. : 1950). 183(5) 3212-8. PMID: 19648271 | PMCID: PMC2735024
- Sharma R, Sung SS, Abaya CE, Ju AC, Fu SM, Ju ST, IL-2 regulates CD103 expression on CD4+ T cells in Scurfy mice that display both CD103-dependent and independent inflammation., 2009; Journal of immunology (Baltimore, Md. : 1950). 183(2) 1065-73. PMID: 19553521 | PMCID: PMC2734909
- Sharma R, Sung SS, Fu SM, Ju ST, Regulation of multi-organ inflammation in the regulatory T cell-deficient scurfy mice., 2009; Journal of biomedical science. 16() 20. PMID: 19272184 | PMCID: PMC2653523
- Zheng L, Sharma R, Kung JT, Deshmukh US, Jarjour WN, Fu SM, Ju ST, Pervasive and stochastic changes in the TCR repertoire of regulatory T-cell-deficient mice., 2008; International immunology. 20(4) 517-23. PMID: 18310063 | PMCID: PMC2841480
- Sharma R, Ju AC, Kung JT, Fu SM, Ju ST, Rapid and selective expansion of nonclonotypic T cells in regulatory T cell-deficient, foreign antigen-specific TCR-transgenic scurfy mice: antigen-dependent expansion and TCR analysis., 2008; Journal of immunology (Baltimore, Md. : 1950). 181(10) 6934-41. PMID: 18981113 | PMCID: PMC2734502
- Sharma R, Jarjour WN, Zheng L, Gaskin F, Fu SM, Ju ST, Large functional repertoire of regulatory T-cell suppressible autoimmune T cells in scurfy mice., 2007; Journal of autoimmunity. 29(1) 10-9. PMID: 17521882 | PMCID: PMC2099300