Project Summary Eosinophilic esophagitis (EoE) is a chronic food allergen- and immune-mediated disease that exerts a significant clinical and financial burden worldwide. Interleukin (IL)-13 is an essential mediator of EoE due to its pleotropic effects on esophageal inflammation and tissue remodeling. We have identified IL-13 as a critical mediator of increased mitochondrial mass in esophageal epithelial cells. We further demonstrate that IL-13-mediated alterations in mitochondrial mass are dependent upon JAK/STAT signaling and contribute to EoE-associated epithelial remodeling. These findings support our overarching hypothesis that IL-13 in the EoE inflammatory milieu activates STAT signaling in esophageal epithelium to drive alterations in mitochondrial biology that promote EoE pathogenesis. To test this hypothesis, we will define the direct molecular mechanisms through which IL-13 signaling regulates mitochondrial biology (Aim 1) and the functional significance of these findings with regard to EoE-associated tissue remodeling (Aim 2). The proposed studies will illuminate the IL- 13/STAT/mitochondria axis as a novel player in EoE pathobiology. The research proposal, coupled with the tailored training plan, will provide outstanding career and professional development opportunities for the applicant under the guidance of the co-mentors who have relevant expertise in esophageal biology (Whelan) and mitochondria (Elrod).