Dysregulated Signaling in Crohns Disease
Technical Report,15 May 2016,14 May 2019
Beth Israel Deaconess Medical Center Boston United States
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Crohns disease CD is a chronic and debilitating inflammatory disorder of the small and large intestine. The lack of concrete molecular mechanistic insight into disease pathogenesis severely hampers the search for new and effective targeted therapies. In particular, the role that protein signal transduction cascades play in CD is not well understood. We are utilizing an approach that integrates mouse modeling, proteomics, and computational analysis to identify signaling pathways that drive the onset and progression of intestinal inflammation in mouse models. We previously identified MIP-1a and MIP-1b as potential therapeutic targets and we have begun the dose-finding studies for neutralizing antibodies that are required for the preclinical evaluation of efficacy in the T cell transfer model of colitis. We have also begun to establish experimental cohorts for the IL-2Ra and IL-10Tlr4 mouse models of colitis so that we can perform signaling analysis. Significant progress has been made on the characterization of colitis in TNFdeltaARE animals. Here, we have completed mass spectrometry analysis of signaling, creating a novel dataset. We are performing bioinformatic analysis and we anticipate progressing to functional studies over the coming year.
- Medicine and Medical Research