van den Brink G.R.: Intestinal mucosal homeostasis and it's deregulation in inflammatory bowel disease and during oncogenesis

Project Details

Description

The first line of research explores pathways that maintain epithelial homeostasis in the gastrointestinal tract and the way these pathways are deregulated during the earliest stages of intestinal carcinogenesis. This research has been funded in the past 5 years by grants from the ERC, NWO (VIDI grant and VICI grant) and KWF. Since the pathways responsible for stem cell specification and maintenance are relatively well characterized, one of our aims has been to identify pathways that restrict stem cell proliferation and mediate stem cell differentiation. examples: our research has identified Indian Hedgehog as a key epithelial-mesenchymal negative feedback regulator produced by the differentiated epithelial cells that restricts stem cell proliferation and expansion. More recently we have found that ER stress is responsible for the initial differentiation of intestinal epithelial stem cells to a transit amplifying cell fate.



The second line of research researches the mechanism of action of drugs used in IBD. The first goal of this research line is to better understand the mechanism of action of existing therapies for IBD in order to increase efficacy, reduce side effects and find novel targets for therapy. This research is currently mainly funded by and in collaboration with the R&D departments of AbbVie (Worcester, Massachusetts) and Crucell (Leiden, the Netherlands). Much of this work aims to exploit our finding that anti-TNFs may primarily work by inducing wound healing macrophages in IBD. One of the aims of this research is to engineer novel anti-TNFs and design new combination therapies that enhance the generation of wound healing macrophages in patients with IBD by screening FDA approved drug libraries (ongoing in collaboration with Daniel Ebner at the Target Discovery Institute at Oxford University).

See also Tackling chronic inflammatory bowel disease : Towards a better treatment (video) and The female touch : The role of sex hormones in colon cancer development (video)
StatusActive
Effective start/end date1/10/2010 → …