Murine models to test parasite products as cures for Inflammatory Bowel Disease

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DESCRIPTION (provided by applicant): Investing in enhancement of Dr. Mansfield's mouse model activities will result in progress in understanding and treating inflammatory disease of the bowel resulting from enteric pathogens and in fostering veterinarians to enter the research arena. Dr. Mansfield graduated from a V.M.D., Ph.D. program in Biomedical Graduate Studies at the University of Pennsylvania in 1990 and finished postdoctoral training at the Animal Parasite Institute in 1994. Currently, she is 11 years from her training, thus, qualifying as a Mid-Career investigator. Her training and research career were spent developing animal models of human and animal infectious enteric diseases. From 1990-2003, she focused on finding naturally occurring animal models for Campylobacter jejuni and Cyst forming coccidia (Sarcocystis neurona, etc.) with the long-term goal to convert these to mouse models. In 2002-04, she successfully achieved funding to implement mouse models for these pathogens and, thus, shifted her focus within comparative medicine from large animal models of these human and animal enteric diseases to murine models. Recent funded and pending grants on mouse pathobiology document this career shift. Simultaneously, she requested relief from administrative duties running the Clinical Parasitology Section of the Diagnostic Center for Population and Animal Health. Caseloads had burgeoned under her leadership from 1500 to >10,000/year placing increasing demands on time for research and mentoring. Dr. Mansfield seeks Career Award funds to enhance her program in mouse pathobiology especially to pursue projects in the funded NIH contract "Michigan State University Microbiology Research Unit: Food and Waterborne Integrated Research Network". These Career Award funds would enable new mouse models including, 1)"Murine models of C. jejuni colonization and enteritis" to determine mechanisms by which C. jejuni and other enteric bacteria stimulate chronic inflammation in the gut, and 2)"Worm mediated control of inflammatory Bowel Disease" to determine immunomodulatory properties of defined parasitic products from Trichuris on colonic inflammation (spontaneous and pathogenmediated). These mouse models will serve as the first modality for testing select parasites and their molecules for efficacy in down modulating chronic inflammation. Dr. Mansfield has documented success mentoring graduate students and seeks to expand her mentoring of D.V.M.s in mouse pathobiology.