Autophagy and resolution of endoplasmic (ER) stress are key cellular processes in the regulation of homeostasis of the intestinal epithelium. Unresolved ER stress is a consequence of accumulating misfolded proteins and leads to an excessive activation of inflammatory signals, altogether called the unfolded protein response (UPR). Autophagy is a cannibalistic process, in which organelles and other cellular structures, but also invading pathogens are degraded. This intrinsic recycling machinery also acts as a compensatory mechanism for ER stress. Disruption of the molecular ER stress-autophagy axis, caused by mutations within IBD risk genes like AGR2, ATG16L1 and XBP1, skews the epithelium towards inflammation and cellular death. Our group therefore set out to understand the role of autophagy defects and unresolved UPR in the pathogenesis of IBD. Previously, we studied the link between (bulk) autophagy and IBD-relevant inflammatory cascades like type-I-interferon signalling. To investigate the underlying molecular mechanisms more in detail, we specifically study the role of selective autophagy processes, e.g. specific autophagy of mitochondria (mitophagy) or endoplasmic reticulum (ER-phagy).  

Beside in vivo and organoid models we employ CRISPR/Cas9-guided deletion of autophagy and ER stress-relevant genes to characterise their role in epithelial homeostasis. Advanced imaging methods like confocal laser microscopy are available prerequisites for proper studies on autophagy flux and ER morphology.