Chandra Mohan, MD, PhD

University of Texas Southwestern Medical Center, Dallas, TX

2008 Biomarkers
2006 Genetics
2001 Kidney

LRI Class of 2008 Consortium Grant with Chaim Putterman, MD, at the Albert Einstein College of Medicine in the Bronx.

Lupus nephritis is common in people with lupus, and can cause irreversible kidney damage. The need for biomarkers (“early predictors”) to detect problems and monitor treatment effectiveness is urgent.

With LRI funding, and working from their respective laboratories in the Bronx and Dallas, Drs. Putterman and Mohan will evaluate the power of five urine biomarkers that have shown promise in predicting the onset and progression of lupus nephritis in mice by testing them in urine from people.

The consortia, a powerful pooling of talent and technology that the LRI was willing to consider for ‘human lupus biology’ research, will also study the value of these biomarkers in monitoring and measuring response to therapy. By using human tissue—in this case, urine from people with lupus—the investigators are more likely to make discoveries directly relevant to humans.

If successful, the study could represent a major breakthrough with potentially immense impact on better managing lupus nephritis.

In 2006, Dr. Mohan received a Novel Research Grant from the LRI to pursue a novel idea in lupus genetics.

The genes a person inherits may make him or her more susceptible to lupus, and the LRI funds various research endeavors to explore this association, so that measures can be taken to anticipate or modify it.

Dr. Mohan noted that under normal circumstances, genes patrol B-cell tolerance checkpoints to curb autoimmune reactions. But it’s still unclear which genes these are. So Dr. Mohan set out to use a newly established method of screening for these genes that involves activating a substance dubbed “sleeping beauty” that can “cut and paste” a mobile sequence of DNA into random locations within B cells.

Dr. Mohan’s work has the potential to reveal invaluable information on the spectrum of molecules able to alter B-cell tolerance and participate in causing the destruction of lupus, and point to new targets for drug therapies.

A summary of Dr. Mohan’s ongoing lupus research and a more extensive list of recent publications can be found at http://www4.utsouthwestern.edu/mohanlab/ or http://www.utsouthwestern.edu/utsw/cda/dept20539/files/131854.html.

With LRI funding in 2001, Dr. Mohan investigated the hypothesis that lupus-prone mouse stains have a genetically determined sensitivity to kidney damage that is independent of their genetic predisposition to produce autoantibodies.

His tests could help identify lupus patients at risk for kidney damage and also provide clues to treatments to prevent such damage.

It was then that he started to collaborate with Dr, Chain Putterman at Albert Einstein College of Medicine in New York to investigate end-organ damage in humans with lupus.

Select publications:

Urine Proteome Scans Uncover Total Urinary Protease, Prostaglandin D Synthase, Serum Amyloid P, and Superoxide Dismutase as Potential Markers of Lupus Nephritis. J Immunol. 2010 Published online January 11. Wu T, Fu Y, Brekken D, Yan M, Zhou XJ, Vanarsa K, Deljavan N, Ahn C, Putterman C, Mohan C.

Strain distribution pattern of susceptibility to immune-mediated nephritis. J Immunol. 2004 172(8):5047-55. Xie C, Sharma R, Wang H, Zhou XJ, Mohan C.

Enhanced susceptibility to end-organ disease in the lupus-facilitating NZW mouse strain. Arthritis Rheum. 2003 48(4):1080-92. Xie C, Zhou XJ, Liu X, Mohan C.

Ongoing funding:

In 2003, Dr. Mohan won a $940,000 NIH grant to continue working on his LRI-funded work, “Immunogenetics – Target Organ Damage in Immune Nephritis.”

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