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 Co-Chair (if applicable)

Arteel, Gavin

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.

Included in

Pharmacology Commons

Share

COinS