Marc Monestier, MD, PhD
Professor, Biomedical Education and Data Science
Professor, Microbiology, Immunology and Inflammation
- Contact Information
- About Me
Dr. Monestier's research is focused on the elucidation of the mechanisms responsible for the development of autoimmune diseases. Exposure to various drugs and chemicals can elicit autoimmune disease in both humans and experimental animals. For instance, an environmental pollutant such as mercury induces in susceptible mouse strains autoantibodies to nucleolar antigens similar to those seen in human scleroderma. We are investigating the regulation of disease development in this mouse model. Our efforts are focused on the role of co-stimulatory molecules, regulatory T cells and Toll-like receptors in controlling susceptibility to chemical agents. We are also exploring the direct effect of heavy metals on B cells and on dendritic cell function. Studies into the mechanisms of chemically-induced autoimmunity are particularly meaningful since environmental factors have been implicated in the pathogenesis of systemic autoimmunity.
Autoantibodies to negatively-charged phospholipids are associated with venous and arterial thrombosis and with spontaneous abortions. In addition, recent evidence suggests that antiphospholipid antibodies are present during atherosclerosis and that they may modulate the disease. We have generated and characterized the binding properties of a large panel of anti-phospholipid mouse monoclonal antibodies. We have observed that one of these monoclonal antibodies decreases plaque formation when passively administered into atherosclerosis-prone mice. We are investigating the mechanisms responsible for the protective effects of this antibody as well as the possibility of actively manipulating the immune system to prevent atherosclerosis.
The autoimmune response to chromatin is at the core of systemic autoimmune syndromes such as lupus. We have shown that autoantibodies recognize a variety of three-dimensional determinants that result from the ordered association of chromatin molecules such as histones and DNA. These antibodies to nucleosome epitopes are characterized by the presence of numerous arginines in their variable regions. These cationic residues are important for binding to the acidic DNA component of the nucleosome and are often the result of unusual immunoglobulin heavy chain gene rearrangements.
We have recently shown that these unusual immunoglobulin gene rearrangements occur more frequently in autoimmune than in normal mice and we are exploring the mechanisms responsible for this intrinsic B cell defect in autoimmunity.
- Education, Training & Credentials
- University of Lyon