Intestinal Bowel Diseases (IBD) affect millions of lives worldwide. However, therapeutic options for IBD treatment are limited. In this proposal, building upon our previous findings, we propose to examine an important protein called ARTS, which has never-before been studied in connection to IBD. We have found that ARTS is able to coordinate the cellular suicide of intestinal stem cells; cells that are critical for maintaining and replenishing the intestinal barrier. Strikingly, in mice lacking ARTS, the induction of ulcerative colitis was blocked and mice were able to exhibit enhanced stem cell-dependent repair. In light of these exciting findings, we have established a unique synergistic team that will identify and develop novel compound inhibitors of ARTS, to promote appropriate cellular and molecular signaling and prevent excessive stem cell death. It is our hope that the results obtained from this study will be translatable for the treatment of IBD in the clinic.