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Abstract or Project Description

There is still no medical cure for inflammatory bowel diseases (IBD) and the clinical management is challenging. In particular, differentiating between Crohn’s disease (CD) and ulcerative colitis (UC) and predicting the clinical course or the response to therapy is difficult.
In this study, we aim to characterize tissue samples from IBD and control patients with a new diagnostic approach using infrared (IR) light and providing a molecular fingerprint of the disease. It is our goal to identify specific diagnostic fingerprints for CD and UC, for the prediction of the clinical course and the treatment response in patients. Finally, we will use a laser-based technique to obtain areas with specific molecular fingerprints from the tissues. Such material will be analyzed for all expressed genes with so called next-generation sequencing to determine the molecular changes associated with disease-specific fingerprints. Thereby, we hope to identify new diagnostic tools and targets for future therapy.

Abstract or Project Description

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.

Abstract or Project Description

Abstract or Project Description

Lymphatic vessels are specialized vessels that transport immune cells and fat out of the gut to maintain health. Surgeons treating Crohn’s disease decades ago argued that impaired lymphatic flow may be a key problem in the disease. However, only recently have tools emerged to study lymphatic vessels in detail. We have data that lymph transport is impaired even in early Crohn’s disease. However, treatments targeting the cytokine TNF reverse the impaired transport. As investigators specializing in different lymphatic research areas, we will synergistically utilize human subjects’ studies with research in mice and rats to map in detail how terminal ileal inflammation alters lymph flow. We will also address whether a gut hormone called GIP that is overproduced in the setting of TNF neutralizing therapy accounts for how therapy against TNF restores lymph flow. If so, mimetics of the hormone may have utility in subjects unable to use therapeutics against TNF.