Chandra Mohan, MD, PhD

Professor
Endowed Title: Walter M. and Helen D. Bader Professorship in Arthritis and Autoimmune Disease Research
Internal Medicine, Immunology
Graduate Program: Immunology

Contact Information

UT Southwestern Medical Center
5323 Harry Hines Boulevard
Dallas, Texas 75390

chandra.mohan@utsouthwestern.edu

Biography

Dr. Mohan’s laboratory has focused its efforts on genetic dissection of SLE pathogenesis. SLE (systemic lupus erythematosus) is a systemic autoimmune disease with a wide spectrum of phenotypes and pathological changes. Equally varied and intriguing are the diverse immunological mechanisms that underlie this disease.

Much of what they have learned about this disease has come from studying mouse models of this disease. Importantly, several genetic loci that confer lupus susceptibility in mice have recently been identified. Sle1, Sle2 and Sle3 are three such important loci. They also know that these three loci impact the immune system in very different ways. Sle1 triggers the formation of high titers of anti-nuclear autoantibodies, which do not appear to be intrinsically pathogenic. Sle2 triggers generalized (i.e., not antigen-specific) B-cell hyperactivity, but this is not sufficient to cause any disease. Sle3, in contrast, leads to T-cell activation, increased CD4:CD8 ratios, reduced activation-induced T-cell death, and low titers of antinuclear autoantibodies. As one would predict, when these individual susceptibility loci are bred together, full-blown lupus ensues.

Ongoing projects in the laboratory are aimed at elucidating the immunopathological mechanisms through which these loci lead to autoimmunity. Specifically, they are dissecting out the respective contributions of these loci to (a) breaching B-cell and/or T-cell tolerance (using antigen receptor transgenic models), (b) shaping the B-cell and T-cell repertoire at different stages of lymphocyte development and differentiation, and (c) effecting glomerular pathology, via autoantibody-dependent and independent pathways.

Additional studies in Dr. Mohan’s laboratory are aimed at defining the molecular pathways that are triggered at each of the above steps leading to disease. Collectively, these studies will help chart out the molecular blueprints for lupus development.

Education

Graduate SchoolNorthwestern University, Computer Sciences (1995)
Graduate SchoolTufts University (1995)
UndergraduateUniversity of Singapore (1984)

Research Interests

B-cell tolerance
Genetics of lupus nephritis
Pathogenic mechanisms in glomerulonephritis
Pathogenic steps leading to autoimmunity and lupus
Predictive biomarkers in lupus and systematic autoimmunity

Publications

Featured
Regulation of B cell tolerance by the lupus susceptibility gene ly108

Kumar KR, Li L, Yan M, Bhaskarabhatla M, Mobley AB, Nguyen C, Mooney JM, Schatzle JD, Wakeland EK, Mohan C , Science , June 2006; (312(5780)):166

Featured
Glomerular proteome arrays - a novel approach to study glomerular-reactive autoantibodies in lupus

Q Li Zhen, C Xie, T Wu, M Mackay, C Aranow, C Putterman, C Mohan. , J Clin Invest , 2005; (115):3428-3439

Featured
Genetic dissection of lupus: T-cell hyperactivity as a consequence of hyperstimulatory antigen presenting cells.

Zhu J, Liu X, Xie C, Yan M, Yu Y, Sobel ES, Wakeland EK, and Mohan C. , J Clin Invest , 2005; (115):1869-1878.

Featured
Pathogenic profiles and molecular signatures of ANAs derived from NZM2410 lupus mice

Liang Z, Xie C, Chen C, Kreska D, Hsu K, Li L, Zhou X-J, and Mohan C , Journal of Experimental Medicine , 2003; (199):381-398

Featured
Genetic Dissection of SLE: Sle1 and Fas impact distinct pathways leading to lymphoproliferative autoimmunity

Shi X, Xie C, Kreska D, Richardson J, Mohan C , Journal of Experimental Medicine , 2002; (196):281-292

CXCR4/CXCL12 hyperexpression plays a pivotal role in lupus pathogenesis.

Andrew Wang, Anna-Marie Fairhurst, Katalin Tus, Srividya Subramanian, Yang Liu, Fangming Lin, Peter Igarashi1, Xin J. Zhou, Frederic Batteux, Donald Wong, Edward K.Wakeland, and Chandra Mohan , J Immunology , 2009; (182):4448-4458

Type I interferons produced by resident renal cells may promote end-organ disease in autoantibody-mediated glomerulonephritis.

Anna-Marie Fairhurst, Chun Xie, Yuyang Fu, Andrew Wang Christopher Boudreaux, Xin J Zhou, Ricardo Cibotti, Anthony Coyle, John E Connolly, Edward K. Wakeland, Chandra Mohan , J Immunol , 2009; (183(10)):6831-6838

Identification of IRAK1 as a disease gene in systemic lupus erythematosus through combined forward genetic and reverse genetic approaches.

Chaim O Jacob, Jiankun Zhu, et al., and Mohan C , Proc Natl Acad Sci USA , 2009; (106(15)):6256-6261

Kallikreins as disease genes in lupus and anti-glomerular antibody-induced nephritis.

Kui Liu, Quan-Zhen Li, Anna-Karin Abelson, Elena Sanchez, Jennifer A. Kelly, et al, and Mohan C. , J Clin Invest , 2009; (119(4)):911-923

Shared signaling networks that fire up in lupus B cells from genetically distinct mouse models - implications for disease pathogenesis and therapy.

Wu, X Qin, Liu K, Z Kurepa, M Bhaskarabhatla, XJ Zhou, Satterthwaite AB, LS Davis and C Mohan , J Clin Invest , 2007; (117):2186-2196

Honors/Awards

Henry Kunkel Young Investigator Award

American College of Rheumatology (2005)

Elected member

American Society of Clinical Investigation (2004)

Pfizer-Scholl Young Investigator Award

American Association of Immunologists, USA (2000)