Defining Molecular Pathways in Inflammatory Bowel Disease (B16-147)

Inflammatory bowel disease encompasses multiple disorders with high unmet need. Despite the use of biologics such as TNF blockers and more recently anti-a4b7 antibody (vedolizumab) and ustekinemab, a significant number of patients do not achieve remission or significant improvement in their disease symptoms. At the same time, data is emerging from other inflammatory diseases that suggest that there is the patient heterogeneity observed in response to therapy may be reflective of distinct molecular pathways that drive the disease. In contrast to asthma and RA, where the advance of this understanding of disease mechanisms has been limited because of the limited ability to biopsy the affected tissues, patients with inflammatory bowel diseases undergo biopsy as part of the diagnosis and monitoring of their disease. Abbvie proposes to apply high sensitivity analytics such as RNAseq and proteomics on subsections of biopsies from IBD patients using laser capture microscopy. The goal of this collaboration is to better define the molecular basis of patient subtypes in Crohn’s Disease and Ulcerative Colitis. The goal of this collaborative study between Northwestern University and AbbVie, Inc. is to better define the molecular basis of patient subtypes in Crohn’s Disease and Ulcerative Colitis. The proposal is separated into two Specific Aims: Aim 1: Optimize methods for RNAseq, mass spectometry (MS) based proteomics, and laser capture microscopy (LCM) on gut biopsies. Aim 2: Define the histological and molecular characterization of epithelial cells in the onset of disease in Crohn’s and Ulcerative Colitis patients. Up to 140 subjects will be studied at Northwestern University in this single-site study (Aim 1: 10 control subjects, 10 subjects with UC, and 20 subjects with CD; Aim 2: 20 Normal samples, 20 UC samples, 40 CD samples, 20 resection samples with IBD). ­The duration of an individual participant’s participation in the study will be one day. We expe