Hypoxia-induced signaling and its therapeutic implications for inflammatory bowel disease and colorectal cancer

Intestinal hypoxia occurs when local oxygen demand exceeds oxygen supply and is therefore an important hallmark of chronic inflammation such as inflammatory bowel disease (IBD), but also colorectal tumors (CRC). To counter the hypoxic challenge and ensure their survival, mucosal cells induce evolutionary conserved adaptive responses mediated by hypoxia-inducible factors (HIFs) under the control of oxygen-sensitive prolyl hydroxylases (PHD1, 2 and 3). However, how the oxygen sensing machinery contributes to the pathogenesis of IBD and CRC is still not fully understood. During my PhD and first postdoctoral fellowship, key players have emerged from my research and for which i aim to further assess their contribution to the pathology of both diseases. This aim will be addressed in the following objectives: 1. Study the role of erythropoietin in IBD 2. Study the role of PHD2 in CRC development 3. Assess the impact of Phd1-deletion on inflammation dependent and independent CRC 4. Study the effect of fibroblast-specific PHD1 targeting on intestinal inflammation and fibrosis The ultimate goal is to identify novel therapeutic targets or treatment strategies that could benefit IBD and/or CRC patients which is the core business of our research group.