Grant: Project Grant

Serotonin also known as 5-hydroxytryptamine (5-HT) is an important molecule in the human body that controls many normal and disease processes. Serotonin action is changed in experimental colitis and inflammatory bowel disease (IBD). Recently we showed that serotonin has a critical role in activating immune cells and in generating colitis, in our laboratory experiments with cells and mice. Another normal process that may be disrupted in diseases such as IBD is autophagy, which is the body's process to clear out old and damaged cells. A powerful new research method called Genome Wide Association Studies has identified genes that put people at higher risk for IBD. Identifying those genes also links IBD to autophagy. Both autophagy and changes in serotonin action are connected to IBD. However, we still don't know if serotonin signalling affects autophagy action in IBD. Our research will explore if defective autophagy and changes in serotonin action are pivotal players in IBD. We hypothesize that more serotonin action increases the severity of gut inflammation by reducing autophagy in the key cells involved in the generation and/or perpetuation of inflammation. We plan to pin down three key points: 1) How do serotonin and autophagy interact in gut inflammation? 2) How do serotonin and autophagy interact in affecting production of pro- inflammatory cytokines in key cells involved in gut inflammation? 3) How does serotonin change signals inside cells to affect autophagy in our immune system and gut inflammation? This research will help us understand the roles of serotonin and autophagy in gut inflammation, and how they interact. Our results will point to new targets for treating various health disorders, including IBD, that exhibit dysregulated autophagy.