Characterization of the modulation of intestinal stem cell behavior in homeostasis and regeneration by the neuronal peptide hormone VIP

• Applicant: Dr. Moritz Middelhoff
• Subject Area: Gastroenterology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 424415217

The intestinal epithelium demonstrates a rapid turnover and self-renews every 3-5 days. This turnover is fueled by the activity of tissue-resident intestinal stem cells (ISC) such as cycling Lgr5-positive crypt base columnar cells located at the bottom of intestinal crypts. The activity and differentiation of ISC is closely regulated by the surrounding cellular and humoral niche. Neuronal cells and neuronal signaling are considered an essential component of the niche, and neuronal transmitters such as acetylcholine prominently modulate ISC activity and differentiation. Interestingly, our preliminary work identified the vasoactive intestinal peptide (VIP) as yet another putative modulator of ISC activity and differentiation. VIP appears as an important mediator of intestinal inflammatory diseases, and additional insights into ISC modulation by VIP could reveal promising insights into the putative therapeutic potential of VIP. Therefore, we here aim to gain a detailed understanding of the modulation of ISC and intracellular pathway signaling by VIP. Furthermore, our preliminary work points at regional differences of intracellular pathway modulation by VIP, such that we subsequently aim to functionally address these regional differences. Finally, we will aim to validate our results in human tissues to evaluate the translational potential.

• DFG Programme: Research Grants