CD74 and Wound Healing

Project Summary The mucosal epithelial barrier becomes disrupted in many conditions such as surgical procedures, trauma, inflammatory bowel diseases, ischemia, infections, radiation, and chemotherapy. Epithelial cell regeneration is essential for mucosal wound closure and healing. Our overall goal is to understand the mechanisms that lead to effective mucosal wound closure. This proposal builds on our recent discovery of an intestinal mucosal wound repair mechanism involving CD74 signaling. CD74 is the receptor for the MIF cytokine. The proposal aims to address significant questions that remain unanswered in the CD74 signaling pathway and wound repair, and are worth exploring. Our research is motivated by three key questions based on our published and preliminary data: What is the mechanism that drives epithelial CD74 receptor expression (Aim 1)? Can we safely and effectively stimulate CD74 (Aim 2)? What are the functional consequences of human genetic variation on CD74 activity (Aim 3)? Knowledge gained from these studies will significantly advance our mechanistic understanding of CD74 biology and mucosal wound repair, and may lead to new therapeutic strategies for promoting mucosal wound healing.