Shu Man Fu, MD, PhD
Margaret M. Trolinger
Professor of Rheumatology
Professor of Medicine & Microbiology
Division of Clinical Rheumatology
University of Virginia School of Medicine
Ph: (434) 924-9627
Fax: (434) 924-9578
Research Interest: Clinical and basic immunology with emphasis on systemic lupus erythematosus (SLE) & rheumatoid arthritis
(RA)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. Recently a new model of mouse SLE (NZM2328) has been described. 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 pathogensis of SLE. In addition, autoantigens which are the target for nephritis in NZM2328.C57L/J.c4 are to be identified. 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. In this regard, bacterial and viral agents sharing cross reactive T and B cell epitopes with human autoantigens are logical candidates for molecular mimics in this process. There is also interest in the pathogenesis of Sjogren's syndrome. In colloboration, the laboratory is interested in the mechanisms of autoantibody diversification and the role of T cells in the pathogenesis of glomerulonephritis and asthma. The laboratory continues to be interested in activation of both T and B cells with emphasis on the surface molecules, CD40 and its ligand, as well as T and B cell antigen receptors.
1. Waters, S.T., Fu, S.M., Gaskin, G., Deshmukh, U.S., Sung,
S.-S.J., Kannapell, C.C., Tung, K.S.K., McEwen, S.B., and McDuffie, M.
Unique aspects of NZM2328 mice. New insights and implications in the
genetics of systemic lupus erythematosus. J. Immunol. 100:372-383,
2. Kim, YB., Sung, S-S.J., Kuziel, W.A., Feldman, S., Fu, S.M., and Rose, Jr., C.E. Enhanced airway Th2 response after allergen challenge in mice deficient in CC chemokine receptor-2 (CCR2). J. Immunol. 166:5183-5192, 2001.
3. Sung, S-S.J., Rose, Jr., C.E., and Fu, S.M. Intratracheal priming with ovalbumin- and ovalbumin 323-339 peptide-pulsed dendritic cells induces airway hyperresponsiveness, lung eosinophilia, goblet cell hyperplasia, and inflammation. J. Immunol. 166:1261-1271, 2001.
4. Deshmukh, U.S., Lewis, J.E., Gaskin, F., Dhakephalkar, P.K., Kannapell, C.C., Waters, S.T., and Fu, S.M. Ro60 peptides induce antibodies to similar epitopes shared among lupus-related autoantigens. J. Immunol. 164:6655-6661, 2000.
5. Kamochi, M., Kamochi, F., Kim, Y.B., Sawh, S., Sanders, J.M., Sarembock, I., Green, S., Young, J.S., Ley, K., Fu, S.M., Rose, Jr., C.E. P-selectin and ICAM-1 mediate endotoxin-induced neutrophil recruitment and injury to the lung and liver. Am. J. Physiol. 277:L310-319, 1999.
8. Deshmukh, U.S., Lewis, J.L., Gaskin, F., Kannapell, C.C., Waters, S.T., Lou, Y-H., Tung, K.S.K., and Fu, S.M. Immune responses to Ro60 and its peptides in mice I: The nature of the immunogen and endogenous autoantigen determine the specificities of the induced autoantibodies. J. Exp. Med. 189:531-540, 1999.
9. Sung, S.-S.J., Taketomi, E.A., Smith, A.M., Platts-Mills, T.A.E., and Fu, S.M. Efficient presentation of house dust mite allergen Der p 2 by monocyte-derived dendritic cells and the role of b2 integrins. Scand. J. Immunol. 49:96-105, 1999.
10. Smith, A.M., Yamaguchi, H., Platts-Mills, T.A.E., and Fu, S.M. Prevalence of IgG anti-Der p 2 antibodies in children from high and low antigen exposure groups: Relationship of IgG and subclass antibody responses to exposure and allergic symptoms. Clin. Immunol. Immunopathol. 86:102-109, 1998.
11. Kornfeld, S.J., Haire, R.N., Strong, S.J., Brigino, E.N., Tang, H., Sung, S.-S.J., Fu, S.M., and Litman, G.W. Extreme variation in X-linked agammaglobulinemia phenotype in a three generation family. J. Allergy Clin. Immunol. 100:702-706, 1997.