The overall research interest of the applicant is on the cellular and molecular pathogenesis of infections with enteric pathogens and the mechanisms governing intestinal inflammatory responses. The long-germ objective is to build an externally funded independent research program in mucosal immunology and mouse pathobiology research at a major U.S. academic institution. The use of mouse models of intestinal infection and inflammation is an integral component of this research program. Studies in physiologically complex model systems are necessary to validate or discard hypothesis generated in cell culture studies, and to develop new strategies for treatment and prevention of infections with foodborne pathogens and attenuation of intestinal inflammation in patients with idiopathic inflammatory bowel disease (IBD). The proposal has two major objectives: 1. To teach courses in mouse pathobiology research and mentor new investigators, both pre and postdoctoral, at UCSD in conducting specific projects in mouse pathobiology research. 2. Conduct studies to define the physiological functions of the thromboxane A2 receptor, TP, in regulating intestinal inflammation in murine models. Preliminary results show that TP is an important proinflammatory regulator in experimental colitis models, suggesting that it might be a promising target for anti-inflammatory treatment strategies in IBD. The applicant is Director of a Mouse Model Core within a NIH-funded P01 Program Project Grant in Mucosal Immunology at UCSD, and has established the necessary laboratory infrastructures for conducting mouse pathobiology research and mentoring of new investigators. The award will provide salary and technical support for the applicant to devote a greater amount of time than otherwise possible to the development of the mouse pathobiology research program of the Mouse Model Core and the mentoring of new investigators in conducting high-quality mouse pathobiology research.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Midcareer Investigator Award in Biomedical and Behavioral Research (K26)
Project #
5K26RR017030-05
Application #
7430417
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Watson, William T
Project Start
2004-08-13
Project End
2009-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
5
Fiscal Year
2008
Total Cost
$96,914
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Meehan, T F; Witherden, D A; Kim, C-H et al. (2014) Protection against colitis by CD100-dependent modulation of intraepithelial ?? T lymphocyte function. Mucosal Immunol 7:134-42
Spehlmann, Martina E; Dann, Sara M; Hruz, Petr et al. (2009) CXCR2-dependent mucosal neutrophil influx protects against colitis-associated diarrhea caused by an attaching/effacing lesion-forming bacterial pathogen. J Immunol 183:3332-43
Dann, Sara M; Spehlmann, Martina E; Hammond, Dustin C et al. (2008) IL-6-dependent mucosal protection prevents establishment of a microbial niche for attaching/effacing lesion-forming enteric bacterial pathogens. J Immunol 180:6816-26
Hruz, Petr; Eckmann, Lars (2008) Caspase recruitment domain-containing sensors and adaptors in intestinal innate immunity. Curr Opin Gastroenterol 24:108-14
Eckmann, Lars; Nebelsiek, Tim; Fingerle, Alexander A et al. (2008) Opposing functions of IKKbeta during acute and chronic intestinal inflammation. Proc Natl Acad Sci U S A 105:15058-63
Ringqvist, Emma; Palm, J E Daniel; Skarin, Hanna et al. (2008) Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells. Mol Biochem Parasitol 159:85-91
Dann, Sara M; Eckmann, Lars (2007) Innate immune defenses in the intestinal tract. Curr Opin Gastroenterol 23:115-20
Davids, Barbara J; Palm, J E Daniel; Housley, Michael P et al. (2006) Polymeric immunoglobulin receptor in intestinal immune defense against the lumen-dwelling protozoan parasite Giardia. J Immunol 177:6281-90
Andersen, Yolanda S; Gillin, Frances D; Eckmann, Lars (2006) Adaptive immunity-dependent intestinal hypermotility contributes to host defense against Giardia spp. Infect Immun 74:2473-6
Eckmann, Lars (2006) Sensor molecules in intestinal innate immunity against bacterial infections. Curr Opin Gastroenterol 22:95-101

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