CHARACTERIZATION OF LYMPHOCYTE SIGNAL TRANSDUCTION IN RESPONSE TO MERCURY EXPOSU

Univ Of Arkansas For Med Scis, Little Rock AR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Environmental and dietary exposures to small amounts of mercury compounds occur throughout an organism's lifespan. While the negative health effects of large-scale exposures have been well-studied, it has been only recently that researchers have begun to examine the effects of lower, chronic exposures. These exposures induce perturbations of the immune system, resulting in the induction of anti-self autoantibody production by inappropriately activated B lymphocytes. This autoantibody production can progress to an autoimmune syndrome, most notably disorders similar to lupus (with anti-DNA autoantibodies) and scleroderma (with anti-DNA and anti-nucleolar antibodies). While much work has been performed on the altered function of mercury-treated cells, little has been examined in relation to the signal transduction pathways in lymphocytes. The proposed work will characterize changes in signal transduction pathway utilization in mercury-treated B lymphocyte cell culture lines upon activation. This work is novel to this field, as the main focus of mercury-exposure research has centered on either higher doses of mercury, or cells other than lymphocytes. Furthermore, this work will be used to expand the project in subsequent stages into primary B lymphocytes and T lymphocyte cell culture lineages. It is expected that this research project will provide preliminary data necessary to bring similar, but expanded studies to the University of Central Arkansas. A secondary goal is to fine-tune this project to include and train undergraduates/graduates. Therefore, this project is vital to the long term development of my research program at UCA. This summer project will lead to identified additional proposals to seek long term federal-level support. The ultimate goal is to pursue a broad and comprehensive characterization of mercury-activated signal transduction pathway alterations in immune system cells. Additionally, it is expected that the relationship with Dr. Gilbert will develop into a long-term collaboration, bringing the expertise of an established and well-published researcher to assist the career development of a newer investigator.