Date on Master's Thesis/Doctoral Dissertation

12-2015

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, PhD

Committee Chair

Matoba, Nobuyuki

Committee Member

Arteel, Gavin

Committee Member

Bodduluri, Haribabu

Committee Member

Galandiuk, Susan

Committee Member

Jala, Venkatakrishna

Committee Member

Palmer, Kenneth

Author's Keywords

ulcerative colitis; cholera toxin B subunit; inflammatory bowel disease; inflammation

Abstract

This dissertation describes the previously unidentified effects of a plant-produced recombinant cholera toxin B subunit (CTBp) on the gastrointestinal (GI) tract and its ability to protect against inflammation in a mouse model of colonic injury and ulcerative colitis (UC). To comprehensively analyze CTBp’s impacts on the GI tract, we employed global analysis methodologies based on multi-color flow cytometry to analyze immune cell populations in GI and systemic lymphatic compartments, gene expression microarray to decipher transcript-level changes in the colon and small intestine, and 16S rRNA sequencing to characterize fecal microbiota. Based on a drastic shift observed in the immune cell profile and gene expression pattern in the distal colon, we built a new working hypothesis that CTBp may enhance mucosal protection in the colon. To address this hypothesis, we used the Caco-2 human colonic cell line and the mouse dextran sulfate sodium (DSS) colitis model. After demonstrating the potential of CTBp as a mucosal healing and anti-colitic agent, the dissertation will be summarized and future directions discussed.

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Pharmacology Commons

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