Shu-Man Fu, MD, PhD

Shu-Man Fu, MD, PhD

Shu-Man  Fu
Degree(s): MD/PhD
Graduate School: Stanford University
Primary Appointment: Margaret M. Trolinger Professor of Rheumatology, Medicine, Clinical Rheumatology
Research Interests:
Human Lymphocyte Biology and Autoimmunity
Email Address: sf2e@virginia.edu

Research Description

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.


Selected Publications

Bagavant H. Deshmukh US. Wang H. Ly T. Fu SM. Role for nephritogenic T cells in lupus glomerulonephritis: Progression to renal failure is accompanied by T cell activation and expansion in regional lymph nodes. [Journal Article. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't] J Immunol. 177(11):8258-8265, 2006 Dec 1.

Fu SM, Deshmukh US, Gaskin F. Pathogenesis of Systemic Lupus Erythematosus Revisited 2011: End Organ Resistance to Damage, Autoantibody Initiation and Diversification, and HLA-DR. J Autoimmun 2011 Sept. 37(2):104-112. [Epub ahead of print Jun 1, 2011] PMCID: PMC3173577. (available 9/1/2012)

Deshmukh US, Sim DL, Dai C, Kannapell CJ, Gaskin F, Rajagopalan G, David CS, Fu SM. HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD. J Autoimmun 2011 Nov 37(3): 254-262. [Epub ahead of print Aug 23, 2011] "[PMC Journal - In Process (Elsevier)]

Waters ST, McDuffie M, Bagavant H, Deshmukh US, Gaskin F, Jiang C, Tung KS, Fu SM. Breaking tolerance to double stranded DNA, nucleosome, and other nuclear antigens is not required for the pathogenesis of lupus glomerulonephritis. [Journal Article. Research Support, N.I.H., Extramural] J Exp Med. 199(2):255-264, 2004 Jan 19. PMCID: PMC2211766.

PubMed Listings for this Faculty Member


Contact Information

Office Address: PO BOX 800133,

Office Phone: 434-924-9627, +1 434-243-0223

Fax Phone: 434-924-9578