Evaluation of the stromal compartment activation in therapy-refractory inflammatory bowel disease patients that require surgical intervention

Inflammatory bowel disease (IBD), in its manifestations Crohn’s disease and ulcerative colitis, is a chronic inflammatory disease that can affect all parts of the digestive tract. Environmental factors, genetic predisposition and an abnormal function of the immune system are thought to cause IBD.
Standard therapies aim at controlling intestinal inflammation and prolonging the time between disease flare-ups. Although significant progress has been made over the last decades, a high proportion of patients still do not respond to these anti- inflammatory therapies, or become resistant during the course of treatment. Failure to therapeutically control chronic inflammation can lead to severe complications in IBD patients, such as fibrosis, which requires surgical intervention. Fibrotic changes in the intestine are driven by an activation of a particular cell type, the fibroblast.

The aim of this project is to find out whether IBD patients that go on to require surgery display an activation of fibroblasts, and which changes in the tissue are associated with this activation. For this, differences in the way the surgically removed fibrotic tissue is programmed will be compared to the programming of non-inflamed ‘normal’ tissue. We believe that certain alterations in this programming, which is controlled by a network of signals, can lead to changes that are specifically associated with inflammation and the requirement for surgery. Differences in the networks of signals which make up this program of inflamed and non-inflamed tissue will help us identify novel, fibroblast-targeting, therapies which will disrupt the inflammation program and hopefully reduce the requirement for surgery.