Modulating the intestinal epithelial barrier defence as a therapeutic target in Ulcerative Colitis and Crohn's disease

The intestinal epithelium is one of the busiest arenas for innate and adaptive immunity. A single layer of epithelial cells separates the host from the luminal microflora. Unexpectedly, this abundant microflora does not elicit overt inflammation in the intestinal mucosa in normal physiological conditions.

My research program focuses on an important area: the pathological consequence of an impaired intestinal epithelial barrier defence in determining host immune response and intestinal microflora. These 3 factors are critical in the pathogenesis of Ulcerative Colitis (UC) and Crohn’s Disease (CD), collectively known as Inflammatory Bowel Disease (IBD).

The multidrug resistance gene-1 (MDR1/ABCB1) encoding an apical epithelial efflux transporter, P-gp 170 plays an important role in epithelial barrier defence. Murine models deficient in P-gp 170 develop intestinal inflammation akin to human IBD. Intestinal P-gp 170 is significantly lower and genetic variants within the MDR1 gene are associated with UC. My work explores the mechanism underlying microbial and immune-active adjuvants in mediating intestinal inflammation in this setting; and the functional modulation of this gene as a therapeutic target.

In parallel, I am developing an inducible human intestinal epithelial model with a novel gene transfer system which allows directional modulation of additional epithelial components of the primary gut barrier defence and innate immunity. This takes advantage of the numerous IBD susceptibility genes involved in the maintenance of epithelial integrity as identified in recent genomewide association (GWAS) studies.

Overall, my work addresses fundamental disease-selective mechanisms that could be utilized to derive novel therapeutic strategies to alleviate/prevent inflammation and improve healing in IBD.

Gut Epithelium

	GI Home Projects OASIS ABCB5 gene Bio-Safety Funding Publications Contact	Modulating the intestinal epithelial barrier defence as a therapeutic target in Ulcerative Colitis and Crohn's disease The intestinal epithelium is one of the busiest arenas for innate and adaptive immunity. A single layer of epithelial cells separates the host from the luminal microflora. Unexpectedly, this abundant microflora does not elicit overt inflammation in the intestinal mucosa in normal physiological conditions. My research program focuses on an important area: the pathological consequence of an impaired intestinal epithelial barrier defence in determining host immune response and intestinal microflora. These 3 factors are critical in the pathogenesis of Ulcerative Colitis (UC) and Crohn’s Disease (CD), collectively known as Inflammatory Bowel Disease (IBD). The multidrug resistance gene-1 (MDR1/ABCB1) encoding an apical epithelial efflux transporter, P-gp 170 plays an important role in epithelial barrier defence. Murine models deficient in P-gp 170 develop intestinal inflammation akin to human IBD. Intestinal P-gp 170 is significantly lower and genetic variants within the MDR1 gene are associated with UC. My work explores the mechanism underlying microbial and immune-active adjuvants in mediating intestinal inflammation in this setting; and the functional modulation of this gene as a therapeutic target. In parallel, I am developing an inducible human intestinal epithelial model with a novel gene transfer system which allows directional modulation of additional epithelial components of the primary gut barrier defence and innate immunity. This takes advantage of the numerous IBD susceptibility genes involved in the maintenance of epithelial integrity as identified in recent genomewide association (GWAS) studies. Overall, my work addresses fundamental disease-selective mechanisms that could be utilized to derive novel therapeutic strategies to alleviate/prevent inflammation and improve healing in IBD. Gut Epithelium
	Updated: Wed, 22nd September, 2010