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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002868-05
Application #
6984062
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
2002-03-01
Project End
2008-12-31
Budget Start
2006-01-01
Budget End
2008-12-31
Support Year
5
Fiscal Year
2006
Total Cost
$126,630
Indirect Cost
Name
North Carolina State University Raleigh
Department
Anatomy/Cell Biology
Type
Schools of Veterinary Medicine
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Nordone, Shila K; Gookin, Jody L (2010) Lymphocytes and not IFN-gamma mediate expression of iNOS by intestinal epithelium in murine cryptosporidiosis. Parasitol Res 106:1507-11
Gookin, Jody L; Foster, Derek M; Coccaro, Maria R et al. (2008) Oral delivery of L-arginine stimulates prostaglandin-dependent secretory diarrhea in Cryptosporidium parvum-infected neonatal piglets. J Pediatr Gastroenterol Nutr 46:139-46
Gookin, Jody L; Stauffer, Stephen H; Stone, Maria R (2008) Induction of arginase II by intestinal epithelium promotes the uptake of L-arginine from the lumen of Cryptosporidium parvum-infected porcine ileum. J Pediatr Gastroenterol Nutr 47:417-27
Zadrozny, Leah M; Stauffer, Stephen H; Armstrong, Martha U et al. (2006) Neutrophils do not mediate the pathophysiological sequelae of Cryptosporidium parvum infection in neonatal piglets. Infect Immun 74:5497-505
Gookin, Jody L; Chiang, Sophia; Allen, Jessica et al. (2006) NF-kappaB-mediated expression of iNOS promotes epithelial defense against infection by Cryptosporidium parvum in neonatal piglets. Am J Physiol Gastrointest Liver Physiol 290:G164-74
Gookin, Jody L; Allen, Jessica; Chiang, Sophia et al. (2005) Local peroxynitrite formation contributes to early control of Cryptosporidium parvum infection. Infect Immun 73:3929-36
Gookin, Jody L; Birkenheuer, Adam J; St John, Victoria et al. (2005) Molecular characterization of trichomonads from feces of dogs with diarrhea. J Parasitol 91:939-43
Yaeger, M J; Gookin, J L (2005) Histologic features associated with tritrichomonas foetus-induced colitis in domestic cats. Vet Pathol 42:797-804
Gookin, Jody L; Duckett, Laurel L; Armstrong, Martha U et al. (2004) Nitric oxide synthase stimulates prostaglandin synthesis and barrier function in C. parvum-infected porcine ileum. Am J Physiol Gastrointest Liver Physiol 287:G571-81
Gookin, Jody L; Stebbins, Martha E; Hunt, Emily et al. (2004) Prevalence of and risk factors for feline Tritrichomonas foetus and giardia infection. J Clin Microbiol 42:2707-10

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