Leading the way to a cure


Molecular Profiling of Key Steps in Lupus Pathogenesis

Mohan, Chandra, MD

University of Texas Southwestern Medical Center at Dallas

Over the first two years of their ALR grant, Dr. Mohan and his colleagues have used a powerful approach known as proteomic analysis to conduct molecular studies in mice that develop lupus-like disease. Proteomics is the systematic analysis of the different types and amounts of proteins in the body. They have identified the molecular steps that occur during such pivotal stages of lupus development as the activation of self-reactive B cells and the development of kidney disease. In particular, the use of proteomics has uncovered several signaling pathways that become progressively activated within the B cells as autoimmunity evolves; it has also highlighted several molecules that may play a prominent role in kidney disease. Further, this research has identified a number of proteins that may be potential therapeutic or diagnostic targets, and these leads will be followed over the next two years. First, the team will test the potential utility of therapeutic agents against specific signaling pathways that are activated in mice with lupus-like disease and ascertain if these pathways are also up-regulated in human lupus. Then, they will assess the disease-predictive value of monitoring eight different molecules that they have confirmed are elevated in the urine of people with active lupus nephritis. To do so, they will monitor a group of people with lupus, who are already in a longitudinal cohort, for two to five years.  

What this study means for people with lupus: These researchers have already uncovered several potential therapeutic and diagnostic targets based on studies of mice with lupus-like disease. Their current research aims to assess the potential benefits of a number experimental agents, as well as some drugs already approved for use in other diseases, by giving them to these mice. If successful, this research will lay the groundwork for clinical studies in humans. The goal is to develop therapies that would be more specific to the underlying cause of lupus and that would have less toxic side effects. Further, the second tier of the study may lead to the development of new tests to diagnose and monitor progression of lupus kidney disease through urine testing rather than kidney biopsy, with its attendant costs and risks.  

1.5 million

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