This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.
Date of Award
Doctor of Philosophy (PhD)
Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. Our work may in part explain the clinical observation that a history of prior UTI is a risk factor for recurrent UTI and may lead to novel therapeutic strategies.
Chair and Committee
Scott J. Hultgren
Thomas J. Hannan, David Sibley, Christina Stallings, Ting Wang,
Russell, Seongmi Kim, "Investigating the Role of Bladder Epithelial Stem Cells in Bladder Mucosal Remodeling and Defense Against Infection" (2021). Arts & Sciences Electronic Theses and Dissertations. 2528.
Available for download on Friday, August 19, 2022