Environmental influences on intestinal homeostasis and inflammation
In this Wellcome-funded project, we are extending our investigations on the physiological functions of AhR in the immune system by identifying the role of AhR in intestinal epithelial cells in homeostasis as well as in inflammatory disorders.
We consider the AhR a molecular entry point for the impact of environmental signals via metabolites derived from diet, microbiota or environmental pollutants. Thus, studying the molecular mechanisms of AhR functions will hopefully shed light on how environmental triggers influence inflammatory responses in the gut.
Our main questions are:
- How do environmental signals transmitted via AhR impact intestinal epithelial cells (IEC) during homeostasis as well as in inflammation
- What is the role of negative feedback via metabolising enzymes (Cyp1a1) and how does its perturbation in intestinal epithelial cells affect homeostasis and inflammation
- What effect does dysregulation of AhR signalling have on intestinal stem cells and colon cancerogenesis
We aim to pursue these questions using mouse models of inflammation and infection. In addition we plan to conduct studies on intestinal organoids from mice as well as human subjects to investigate consequences of dysregulated AhR activity on potential therapeutic intervention with dietary AhR ligands.