Shu Man Fu
- Email: sf2e@virginia.edu
- Phone: 434-924-9627
- Fax: 434-924-9578
Primary Appointment
Professor, Medicine- Rheumatology and Immunology
Education
- MD, Stanford Medical School
- PhD, Immunology, Rockefeller University, New York, NY
- Residency, Internal Medicine, Stanford University
Research Interests
Human lymphocyte biology and autoimmunity
Research Description
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.
Personal Statement
Training
- Interdisciplinary Training Program in Immunology
Selected Publications
2022
Zhao, Z., Xu, B., Wang, S., Zhou, M., Huang, Y., Guo, C., . . . Fu, S. M. (2022). Tfh cells with NLRP3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity. ANNALS OF THE RHEUMATIC DISEASES, 81(7), 1006-1012. doi:10.1136/annrheumdis-2021-221985
2021
Zhao, Z., Qiao, H., Ge, Y., Kannapel, C. C., Sung, S. -S. J., Gaskin, F., . . . Fu, S. M. (2021). Autoimmune experimental orchitis and chronic glomerulonephritis with end stage renal disease are controlled by Cgnz1 for susceptibility to end organ damage. CLINICAL IMMUNOLOGY, 224. doi:10.1016/j.clim.2021.108675
2020
Sung, S. -S. J., & Fu, S. M. (2020). A novel immunofluorescence detection method for renal cell-type specific in situ cytokine production by confocal microscopy. METHODSX, 7. doi:10.1016/j.mex.2020.100935
2019
Sung, S. -S. J., & Fu, S. M. (2020). Interactions among glomerulus infiltrating macrophages and intrinsic cells via cytokines in chronic lupus glomerulonephritis. JOURNAL OF AUTOIMMUNITY, 106. doi:10.1016/j.jaut.2019.102331
Guo, C., Fu, R., Zhou, M., Wang, S., Huang, Y., Hu, H., . . . Fu, S. M. (2019). Pathogenesis of lupus nephritis: RIP3 dependent necroptosis and NLRP3 inflammasome activation. JOURNAL OF AUTOIMMUNITY, 103. doi:10.1016/j.jaut.2019.05.014
Stremska, M. E., Dai, C., Venkatadri, R., Wang, H., Sabapathy, V., Kumar, G., . . . Sharma, R. (2019). IL233, an IL-2-IL-33 hybrid cytokine induces prolonged remission of mouse lupus nephritis by targeting Treg cells as a single therapeutic agent. JOURNAL OF AUTOIMMUNITY, 102, 133-141. doi:10.1016/j.jaut.2019.05.005
Guo, C., Zhou, M., Zhao, S., Huang, Y., Wang, S., Fu, R., . . . Fu, S. M. (2019). Innate lymphoid cell disturbance with increase in ILC1 in systemic lupus erythematosus. CLINICAL IMMUNOLOGY, 202, 49-58. doi:10.1016/j.clim.2019.03.008
2018
Zhao, Z., Ren, J., Dai, C., Kannapell, C. C., Wang, H., Gaskin, F., & Fu, S. M. (2019). Nature of T cell epitopes in lupus antigens and HLA-DR determines autoantibody initiation and diversification. ANNALS OF THE RHEUMATIC DISEASES, 78(3), 380-390. doi:10.1136/annrheumdis-2018-214125
2017
Xu, B., Wang, S., Zhou, M., Huang, Y., Fu, R., Guo, C., . . . Yang, N. (2017). The ratio of circulating follicular T helper cell to follicular T regulatory cell is correlated with disease activity in systemic lupus erythematosus. CLINICAL IMMUNOLOGY, 183, 46-53. doi:10.1016/j.clim.2017.07.004
Sung, S. -S. J., Ge, Y., Dai, C., Wang, H., Fu, S. M., Sharma, R., . . . Lawler, J. R. (2017). Dependence of Glomerulonephritis Induction on Novel Intraglomerular Alternatively Activated Bone Marrow-Derived Macrophages and Mac-1 and PD-L1 in Lupus-Prone NZM2328 Mice. JOURNAL OF IMMUNOLOGY, 198(7), 2589-2601. doi:10.4049/jimmunol.1601565
Fu, R., Guo, C., Wang, S., Huang, Y., Jin, O., Hu, H., . . . Fu, S. M. (2017). Podocyte Activation of NLRP3 Inflammasomes Contributes to the Development of Proteinuria in Lupus Nephritis. ARTHRITIS & RHEUMATOLOGY, 69(8), 1636-1646. doi:10.1002/art.40155
2016
Fu, S. M., Wang, H., Dai, C., Sung, S. -S. J., & Gaskin, F. (2017). Pathogenesis of proliferative lupus nephritis from a historical and personal perspective. CLINICAL IMMUNOLOGY, 185, 51-58. doi:10.1016/j.clim.2016.07.024
Fu, S. M., & Winchester, R. (2016). A special issue to commemorate the 100th birthday of Henry G. Kunkel, father of clinical immunology: A continuing appreciation of the man, his scientific contributions and his insights to clinical investigation and mentoring. CLINICAL IMMUNOLOGY, 172, 2-20. doi:10.1016/j.clim.2016.07.016
Fu, S. M. (2016). Reflections on my association with Henry G. Kunkel. CLINICAL IMMUNOLOGY, 172, 23-26. doi:10.1016/j.clim.2016.08.005
Chan, A. Y., Punwani, D., Kadlecek, T. A., Cowan, M. J., Olson, J. L., Mathes, E. F., . . . Puck, J. M. (2016). A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70. JOURNAL OF EXPERIMENTAL MEDICINE, 213(2), 155-165. doi:10.1084/jem.20150888
2015
Zhang, H., Huang, Y., Wang, S., Fu, R., Guo, C., Wang, H., . . . Fu, S. M. (2015). Myeloid-derived suppressor cells contribute to bone erosion in collagen-induced arthritis by differentiating to osteoclasts. JOURNAL OF AUTOIMMUNITY, 65, 82-89. doi:10.1016/j.jaut.2015.08.010
Zhao, J., Wang, H., Huang, Y., Zhang, H., Wang, S., Gaskin, F., . . . Fu, S. M. (2015). Glycogen Synthase Kinase 3β Promotion of Renal Damage Through Activation of the NLRP3 Inflammasome in Lupus-Prone Mice. ARTHRITIS & RHEUMATOLOGY, 67(4), 1036-1044. doi:10.1002/art.38993
Zhang, H., Wang, S., Huang, Y., Wang, H., Zhao, J., Gaskin, F., . . . Fu, S. M. (2015). Myeloid-derived suppressor cells are proinflammatory and regulate collagen-induced arthritis through manipulating Th17 cell differentiation. CLINICAL IMMUNOLOGY, 157(2), 175-186. doi:10.1016/j.clim.2015.02.001
Fu, S. M., Dai, C., Zhao, Z., & Gaskin, F. (2015). Anti-dsDNA Antibodies are one of the many autoantibodies in systemic lupus erythematosus.. F1000Research, 4(F1000 Faculty Rev), 939. doi:10.12688/f1000research.6875.1
Chowdhary, V. R., Dai, C., Tilahun, A. Y., Hanson, J. A., Smart, M. K., Grande, J. P., . . . David, C. S. (2015). A Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus. JOURNAL OF IMMUNOLOGY, 195(10), 4660-4667. doi:10.4049/jimmunol.1501073
2014
Dai, C., Wang, H., Sung, S. -S. J., Sharma, R., Kannapell, C., Han, W., . . . Fu, S. M. (2014). Interferon alpha on NZM2328.Lc1R27: Enhancing autoimmunity and immune complex-mediated glomerulonephritis without end stage renal failure. CLINICAL IMMUNOLOGY, 154(1), 66-71. doi:10.1016/j.clim.2014.06.008
Dai, C., Deng, Y., Quinlan, A., Gaskin, F., Tsao, B. P., & Fu, S. M. (2014). Genetics of systemic lupus erythematosus: immune responses and end organ resistance to damage. CURRENT OPINION IN IMMUNOLOGY, 31, 87-96. doi:10.1016/j.coi.2014.10.004
Fu, S. M., Cunningham-Rundles, C., Diamond, B., Rotrosen, D., Stohl, W., & Terhorst, C. (2014). Lloyd Mayer, MD, 1952-2013, In Memoriam. CLINICAL IMMUNOLOGY, 150(2), A1-A2. doi:10.1016/j.clim.2014.01.001
Szymula, A., Rosenthal, J., Szczerba, B. M., Bagavant, H., Fu, S. M., & Deshmuk, U. S. (2014). T cell epitope mimicry between Sjogren's syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria. CLINICAL IMMUNOLOGY, 152(1-2), 1-9. doi:10.1016/j.clim.2014.02.004
2013
Zhao, J., Wang, H., Dai, C., Wang, H., Zhang, H., Huang, Y., . . . Fu, S. M. (2013). P2X7 Blockade Attenuates Murine Lupus Nephritis by Inhibiting Activation of the NLRP3/ASC/Caspase 1 Pathway. ARTHRITIS AND RHEUMATISM, 65(12), 3176-3185. doi:10.1002/art.38174
Lewis, J. E., Fu, S. M., & Gaskin, F. (2013). Autoimmunity, End Organ Damage, and the Origin of Autoantibodies and Autoreactive T Cells in Systemic Lupus Erythematosus. DISCOVERY MEDICINE, 15(81), 85-92.
Ge, Y., Jiang, C., Sung, S. -S. J., Bagavant, H., Dai, C., Wang, H., . . . Fu, S. M. (2013). Cgnz1 allele confers kidney resistance to damage preventing progression of immune complex-mediated acute lupus glomerulonephritis. JOURNAL OF EXPERIMENTAL MEDICINE, 210(11), 2387-2401. doi:10.1084/jem.20130731
2012
Ju, S. -T., Sharma, R., Gaskin, F., & Fu, S. M. (2012). IL-2 controls trafficking receptor gene expression and Th2 response for skin and lung inflammation. CLINICAL IMMUNOLOGY, 145(1), 82-88. doi:10.1016/j.clim.2012.07.015
Ju, S. -T., Sharma, R., Gaskin, F., Kung, J. T., & Fu, S. M. (2012). The Biology of Autoimmune Response in the Scurfy Mice that Lack the CD4+Foxp3+ Regulatory T-Cells.. Biology, 1(1), 18-42. doi:10.3390/biology1010018
Sharma, R., Sung, S. -S. J., Gaskin, F., Fu, S. M., & Ju, S. -T. (2012). A novel function of IL-2: Chemokine/chemoattractant/retention receptor genes induction in Th subsets for skin and lung inflammation. JOURNAL OF AUTOIMMUNITY, 38(4), 322-331. doi:10.1016/j.jaut.2012.02.001
Szymula, A., Szczerba, B., Bagavant, H., Fu, S. M., & Deshmukh, U. (2012). A case for microbial involvement in the activation of lupus-antigen reactive T cells. JOURNAL OF IMMUNOLOGY, 188.
Szymula, A., Szczerba, B., Bagavant, H., Fu, S. -M., & Deshmukh, U. (2012). Oral and Gut Microbiota Influence Immune Responses to Sjogren's Syndrome Associated Antigen Ro60.. ARTHRITIS AND RHEUMATISM, 64(10), S1135.
Chowdhary, V. R., Dai, C., Fu, S. M., & David, C. S. (2012). HLA-DR3 Controls Autoantibody Response to Sm in NZM2328. DR3+.AE0 Transgenic Mice.. ARTHRITIS AND RHEUMATISM, 64(10), S620-S621.
Ge, Y., Brown, M. G., Wang, H., & Fu, S. M. (2012). Genetic approach to study lupus glomerulonephritis.. Methods in molecular biology (Clifton, N.J.), 900, 271-290. doi:10.1007/978-1-60761-720-4_13
2011
Deshmukh, U. S., Sim, D. L., Dai, C., Kannapell, C. J., Gaskin, F., Rajagopalan, G., . . . Fu, S. M. (2011). HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD. JOURNAL OF AUTOIMMUNITY, 37(3), 254-262. doi:10.1016/j.jaut.2011.07.002
Fu, S. M., Deshmukh, U. S., & Gaskin, F. (2011). Pathogenesis of systemic lupus erythematosus revisited 2011: End organ resistance to damage, autoantibody initiation and diversification, and HLA-DR. JOURNAL OF AUTOIMMUNITY, 37(2), 104-112. doi:10.1016/j.jaut.2011.05.004
Sharma, R., Sung, S. -S. J., Ju, C. -Y. A., Deshmukh, U. S., Fu, S. M., & Ju, S. -T. (2011). Regulatory T-Cell (Treg) hybridoma as a novel tool to study Foxp3 regulation and Treg fate. JOURNAL OF AUTOIMMUNITY, 37(2), 113-121. doi:10.1016/j.jaut.2011.05.008
Sharma, R., Fu, S. M., & Ju, S. -T. (2011). IL-2: A two-faced master regulator of autoimmunity. JOURNAL OF AUTOIMMUNITY, 36(2), 91-97. doi:10.1016/j.jaut.2011.01.001
Sharma, R., Sharma, P. R., Kim, Y. -C., Leitinger, N., Lee, J. K., Fu, S. M., & Ju, S. -T. (2011). 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 (vol 186, pg 1268, 2011). JOURNAL OF IMMUNOLOGY, 186(8), 5012-5013. doi:10.4049/jimmunol.1190010
Sharma, R., Sharma, P. R., Kim, Y. -C., Leitinger, N., Lee, J. K., Fu, S. M., & Ju, S. -T. (2011). 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. JOURNAL OF IMMUNOLOGY, 186(2), 1268-1278. doi:10.4049/jimmunol.1002677
2010
Rose, C. E. J., Lannigan, J. A., Kim, P., Lee, J. J., Fu, S. M., & Sung, S. -S. J. (2010). Murine lung eosinophil activation and chemokine production in allergic airway inflammation. CELLULAR & MOLECULAR IMMUNOLOGY, 7(5), 361-374. doi:10.1038/cmi.2010.31
Jiang, C., Deshmukh, U. S., Gaskin, F., Bagavant, H., Hanson, J., David, C. S., & Fu, S. M. (2010). Differential Responses to Smith D Autoantigen by Mice with HLA-DR and HLA-DQ Transgenes: Dominant Responses by HLA-DR3 Transgenic Mice with Diversification of Autoantibodies to Small Nuclear Ribonucleoprotein, Double-Stranded DNA, and Nuclear Antigens. JOURNAL OF IMMUNOLOGY, 184(2), 1085-1091. doi:10.4049/jimmunol.0902670