We investigate the mechanisms that underlie inflammation at mucosal surfaces.
A single layer of intestinal epithelial cells – which may be considered the evolutionary most ancient innate immune cell type – separates the complex and densely populated habitat of the microbiota from the sterile host tissue of the gut, which itself harbours the majority of the host’s bona fide immune cells. A loss of the mutualistic relationship between host and microbiota is thought to be at the basis of the inflammatory bowel diseases Crohn’s disease and ulcerative colitis.
Using a variety of techniques, including complex genetic models, we explore the major biological mechanisms that are affected by risk genes of inflammatory bowel disease. This approach opens up a window to explore the environmental factors that may trigger disease in genetically susceptible individuals, and which are the cause for the steep increase in incidence and prevalence of these diseases around the world. Following this path, we have reported mechanisms of how hypomorphic autophagy and mediators of the unfolded protein response lead to inflammatory bowel disease, defining a key pathway of Crohn’s disease pathogenesis. Further following this paradigm, we have more recently discovered an entirely novel immunometabolic pathway that determines risk for Crohn’s disease, leprosy, and systemic juvenile idiopathic arthritis.
An important part of our agenda is to translate novel insights into therapeutic opportunities for our patients. This ranges from proof-of-concept studies and early phase clinical development programmes of novel mechanisms of action up to late phase pivotal registration trials.
We are generously supported by