Objective Endoplasmic reticulum (ER) stress allows cells to cope with misfolded proteins through the Unfolded Protein Response (UPR). We have recently reported that unabated ER stress, a consequence of genetic deletion of X-box binding protein-1 (XBP1), in intestinal epithelial cells (IECs) leads to intestinal inflammation reminiscent of inflammatory bowel disease (IBD), and polymorphisms in XBP1 were associated with Crohn s disease and ulcerative colitis.The current proposal is based on this central discovery, and rests on three major pillars. 1. Elucidation of the molecular pathways that connect unabated ER stress with inflammation, with the potential to identify novel therapeutics. 2. Testing the hypothesis that XBP1 deficiency may regulate colorectal cancer development, both sporadic and inflammation-associated. 3. Addressing the hypothesis that XBP1 and ER stress may contribute to the molecular pathology of primary sclerosing cholangitis (PSC) via affecting cholangiocyte biology. Insight from these studies may have implications well beyond mucosal inflammation as ER stress mechanisms have been suggested to play a role in a wide variety of diseases. Fields of science medical and health sciencesclinical medicinegastroenterologyinflammatory bowel diseasenatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologycolorectal cancermedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2010-StG_20091118 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution € 1 500 000,00 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Principal investigator Arthur Kaser (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE United Kingdom EU contribution € 1 500 000,00 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Principal investigator Arthur Kaser (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
