The Research Proposal: The long-term goal of these laboratories are to better understand the cellular mechanisms of diarrhea and tissue injury, define the integrated mechanisms of mucosal defense and repair in infectious enteritis, and identify rational approaches to nutritional and pharmacologic enhancement of epithelial repair. Our preliminary studies showed that inducible nitric oxide synthase is expressed intensely by damaged enterocytes after acute mucosal bile salt injury. Exogenous L-arginine promotes epithelial repair after the injury; an effect that depends upon NO synthesis. The present studies hypothesize that iNOS is a key mediator of epithelial defense and repair in Cryptosporidium infection by hastening elimination of infected enterocytes and restitution. We will use a well-characterized experimental model of neonatal porcine cryptosporidiosis and migration studies of porcine jejunal enterocytes to examine the role of NOS in epithelial injury and restitution at both the cellular and whole tissue level and in the presence and absence of inflammatory mediators. The Candidate is a veterinarian who has completed a residency in Internal Medicine and is a board certified Diplomate of the American College of Veterinary Internal Medicine. The candidate has also completed a Ph.D. in Physiology with a minor in Biotechnology. The dissertation examined the role of L-arginine and prostaglandins in restoration of mucosal barrier function after acute mucosal bile salt injury. As a veterinary internist and gastrointestinal physiologist, the candidate is committed to a career in academia pursuing basic research, with a lesser commitment to clinical service and teaching. The Environment: The sponsor and co-sponsors of this proposal each can provide unique contributions to the proposed research and professional development of the candidate. The laboratories in which the candidate is engaged are capable of providing the room, equipment, animal handling facilities, and support staff necessary for completion of this proposal. The laboratories are contained within the College of Veterinary Medicine (NCSU) and School of Medicine (UNC) which provides intensive interdisciplinary training and support through the Core Center for Gastrointestinal Biology and Disease, Biotechnology Program, seminars, and journal clubs.
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