Characterizing the transmural nature of ulcerative colitis and its associated disease-related outcomes using intestinal ultrasound: a paradigm shift in treatment targets - PROJECT SUMMARY/ABSTRACT Ulcerative colitis (UC) is an idiopathic chronic inflammatory condition of the large intestine. Current treatment targets are aimed at healing the inflamed mucosa, however, most patients who achieve mucosal healing do not have sustained remission and continue to have reduced quality of life and a variety of comorbidities. This proposal provides a paradigm shift in the approach to UC as disease that is not mucosal, but transmural in its nature. The broad objective of this research proposal is to test the hypothesis that transmural structural alterations (TMA) to the bowel wall in UC lead to poor clinical outcomes as compared to UC that has a preserved bowel wall structure. I will study this using a novel approach of in vivo assessment of the bowel by intestinal ultrasound (IUS), and determine the predictors for TMA, the associated outcomes with such changes, and whether these changes are reversible. If successful, this proposal will identify new therapeutic targets and endpoints in clinical trials. To accomplish this, I propose the following specific aims: 1) Determine the predictors of TMA to the bowel wall in patients with UC with either active or remitted mucosal inflammation. 2) Determine disease-related outcomes of UC patients who have TMA and transmural healing (TH) of the large intestine. 3)Determine the relationship between TMA of the rectal wall and rectal function. I seek to develop a career as an independent physician-scientist focused on outcomes research and disease modification in IBD. My career goals require me to obtain additional training in patient-reported outcomes, longitudinal data analysis and advanced bowel ultrasound techniques. The 5-year career development program outlined in this application will be based at the University of Chicago, which has attained distinction in the clinical care and research of IBD and is a leading IUS center in the US. Dr. David T. Rubin, Professor of Medicine, is my primary mentor and will provide expertise in endpoint development and application of emerging diagnostic tools for the management of UC. Dr. Eugene Chang, Professor of Medicine, is my co-mentor and an expert on the pathophysiology and immunology of IBD. An interdisciplinary Advisory Committee will provide guidance for me during this development period: Dr. John Hart, expert in IBD pathology, Dr. Mihai Giurcanu, expert in biostatistics, Dr. Maria Abreu, established and NIH funded translational scientist in IBD with IUS experience, Dr. Corey A. Siegel, expert in outcomes research in IBD, and Dr. Shintaro Sagami, expert in the use of US for UC. With the mentorship, training, and resources available to me, I will be uniquely equipped to undertake an independent research career in outcomes research in IBD by the completion of this career development award.
