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GI Toxicity

The relationship between epithelial cell fate, microbiota composition and inflammation in the intestine

How perturbation of the homeostatic mechanisms governing epithelial cell fate in the intestine influence the gut microbiota and the susceptibility to colitis. The influence of structural proteins on key signalling pathways and their downstream transcriptional machinery are discussed.

CCDC88B and its Importance in Inflammatory Bowel Disease

Epistem have extensive experience of running in vivo colitis models including off-the-shelf models of adoptive T cell transfer-mediated and DSS-induced acute colitis; in addition, we are happy to develop and run bespoke models in collaboration with Sponsors.

Adoptive T Cell Transfer Models of Colitis

This model offers the ability to study test items using a range of dosing regimens, from dosing in a prophylactic manner through to examining efficacy in ameliorating early stage or established disease.

CCL20 as a biomarker of drug efficacy in IBD

The chemokine CCL20 (Mip-3α) plays an important role in recruiting Th17 cells (which express the corresponding receptor, CCR6) to sites of inflammation, thus playing a role in the pathogenesis of chronic inflammatory conditions such as Crohn's disease. In a recent paper in the Journal of Crohn's and Colitis, Giovanni Monteleone and colleagues presented data from clinical and laboratory studies on Mongersen, a Smad7 antisense oligonucleotide.

A new paper demonstrates that BMP limits Lgr5+ stem cell number in intestinal epithelial cells

The paper demonstrates that BMP acts via Smad to transcriptionally repress a range of stem cell associated genes, including Lgr5, and that this is independent of the Wnt//β‑catenin signalling pathway.

Accessing Disease End-Points in IBD Models

High quality histopathology analysis is standard for all our IBD service models. In addition, Epistem offer a wide range of analytical services that allow Sponsors to acquire quantitative experimental data for a variety of disease-relevant end-points.

New paper demonstrating the microbiota impact on cell proliferation via microRNA expression changes in intestinal epithelial stem cells

Intestinal flora are known to impact the immune system and metabolism, with chronic exposures to certain flora linked to conditions such as inflammatory bowel disease and fibrosis. Breeches of the epithelial barrier and systemic infection can lead to more acute problems such as sepsis.

Citrulline as a Biomarker of GI Toxicity

Citrulline is produced by small bowel enterocytes, with circulating citrulline levels correlating with enterocyte mass. Changes in enterocyte number (or in some cases function) are therefore reflected in plasma levels. As a result, citrulline levels may be a biomarker for various GI syndromes