Thomas Jefferson University - S.M. Ziaur Rahman
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S.M. Ziaur Rahman
Microbiology and Immunology
Thomas Jefferson University
Jefferson Medical College
Department of Microbiology and Immunology
Research Assistant Professor
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Mailing Address
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1020 Locust Street, Room 461 JAH
Philadelphia, Pennsylvania 19107
United States
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Qualifications
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M.D, Beijing Medical University, China, 1993
Ph.D, National University of Singapore, 2002
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Expertise and Research Interests
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My lab focuses on (1) studying the basic mechanisms of peripheral tolerance notably germinal center (GC) and antibody-forming cell (AFC) pathways and how altered mechanisms might lead to the production of autoantibodies and the development of lupus nephritis under autoimmune conditions such as SLE and (2) mapping and identifying the gene(s) that might play critical role in immune-mediated end-organ damage such as kidney (nephritis).
(1) SLE (systemic lupus erythematosus) is a complex polygenic disease. Most of our understanding about the autoimmune disease such as SLE to date has come from the studies of animal models. The New Zealand Black (NZB)/NZ White (NZW)-derived NZM2410 strain develops a disease that resembles human SLE. Three major genomic intervals (Sle1, Sle2 and Sle3) were identified by the Wakeland group in the NZM2410 strain. B6 mice congenic for each of these loci exhibit different component phenotypes. For instance, B6.Sle1 mice spontaneously develop high titers of ANAs but these can mediate high penetrance of severe glomerulonephritis only in combination with other SLE susceptibility loci (Sle2, Sle3/Sle5, Yaa and lpr). Two of the most potent loci are Sle1 and Sle3. Sle3 in combination with Sle1 mediates severe lupus nephritis. B6.Sle3 has been shown to be associated with ANAs, T cell hyperactivity, elevated ratios of CD4/CD8 T cells and hyperstimulatory antigen-presenting cells (APCs). However, it is not clear whether this process is due to loss of central or peripheral tolerance. Using B cell antigen receptor transgenic mouse line (B6.HKIR) that produces autoreactive (DNA-reactive) B cells, we are investigating how Sle1 and Sle3 might be altering the peripheral B cell tolerance operative during GC and AFC pathways leading to the development of autoantibodies and autoimmune disease SLE.
(2) The development of immune-mediated kidney disease is a major hallmark of SLE. Recent studies in mice, using rabbit sera reactive to mouse kidney glomeruler basement membrane (GBM) to induce nephritis, have suggested that some laboratory strains (such as NZW, 129/svJ and C58/J) are more prone to immune-mediated kidney damage compared with C57BL/6 and BALB/c control strains. Currently, the studies are conducted in our lab to determine whether the kidney intrinsic events or the difference in infiltrating immune cells are responsible for a renal disease as a consequence of immunological insult. Also, the genetic basis of this immune-mediated kidney disease is poorly understood. Through genetic mapping studies and gene expression profile, our goal is to identify the genetic loci and candidate genes that specifically contribute to immune mediated kidney disease. Once the actual genes playing a pivotal role in immune mediated renal disease are identified in mice, we will continue to study these genes in lupus patients with kidney disease and develop therapeutic approaches by targeting these genes.
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Keywords
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B lymphocyte, peripheral B cell tolerance, autoimmunity, lupus
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Languages
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Bengali, English and Chinese (Mandarin)
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Publications
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- Ziaur S.M. Rahman, Soe-Kyaw Tin, Buenaventura PNL, Ho CH, Yap EP, Yong RY and Koh DR: A novel susceptibility locus on chromosome 2 in the (New Zealand Black x New Zealand White) F1 hybrid mouse model of systemic lupus erythematosus. The Journal of Immunology, 2002, 168: 3042-49.
- Ziaur S.M. Rahman, Sambasiva P. Rao, Sue Kalled and Tim Manser: Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice. The Journal of Experimental Medicine, 2003, 198: 1157-69.
- Ziaur S.M. Rahman and Tim Manser: B cells expressing Bcl-2 and a signaling-impaired BAFF (B Cell Activating Factor Belonging to the TNF Family)-specific receptor fail to mature and are deficient in the formation of lymphoid follicles and germinal centers: The Journal of Immunology, 2004, 173: 6179-88.
- Ziaur S.M. Rahman and Tim Manser: Failed upregulation of the inhibitory IgG Fc receptor FcgammaRIIB on germinal center B cells in autoimmune-prone mice is not associated with deletion polymorphisms in the promoter region of the FcgammaRIIB gene: The Journal of Immunology, 2005, 175: 1440-9.
- Hongxia Z. Imtiyaz, Steven Rosenberg, Yuheng Zhang, Ziaur S.M. Rahman, Ying J. Hou, Tim Manser and Jianke Zhang: The Fas-Associated Death Domain Protein (FADD) is required in B cell development, apoptosis, and TLR-induced proliferative responses: The Journal of Immunology, 2006, 176: 6852-61.
- Ziaur S.M. Rahman, Boris Alabyev and Tim Manser: FcgammaRIIB regulates autoreactive primary antibody-forming cell, but not germinal center B cell, activity: The Journal of Immunology, 2007, 178: 897-907.
- Boris Alabyev, Ziaur S.M. Rahman and Tim Manser: Quantitatively reduced participation of anti-nuclear antigen B cells that down regulate BCR during primary development in the germinal center/memory B cell response to foreign antigen: The Journal of Immunology, 2007, 178: 56235634.
- Ziaur S.M. Rahman, Haitao Niu, Daniel Perry, Edward Wakeland, Tim Manser, and Laurence Morel: Expression of the autoimmune Fcgr2b NZW allele fails to be up-regulated in germinal center B cells and is associated with increased IgG production: Genes and Immunity, 2007, 1-9.
- Chun Xie, Ziaur S.M. Rahman, Shangkui Xie, Jiankun Zhu, Yong Du, Xiangmei Qin, Hui Zhou, Xin J. Zhou, and Chandra Mohan: Strain distribution pattern of immune nephritisa follow-up study: International Immunology, 2008, 20: 719-728.
- Raja Vuyyuru, Chandra Mohan, Tim Manser, and Ziaur S. M. Rahman: The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints. The Journal of Immunology, 2009, 183: 5716-27.
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Individual Expertise profile of
S.M. Ziaur Rahman, Copyright © S.M. Ziaur Rahman.
Last Updated
by S.M. Ziaur Rahman : Monday, November 2, 2009 3:33:55 PM
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