Research Projects

Epithelial linings of organs that interact with the environment use innate immune defenses to protect against xenobiotic exposures and pathogens. Understanding the role of specific immune modulating genes expressed by these barriers can help design targeted therapies to prevent chronic inflammation and tissue damage following infection. The lower urinary tract, consisting of the bladder and urethra, acts as a barrier against urine components and urinary pathogens originating from the gut. Defensive strategies employed by the lower urinary tract epithelial lining include the expression of mucus and antimicrobial peptides, as well as innate immune modulators that inhibit pathogen access to the underlying tissue. Recent advances in single cell transcriptomics have enabled the resolution of cell type-specific gene expression in the urethra and bladder epithelium, revealing a plethora of immune modulating and defense genes expressed by these barriers. One key immune modulating gene that emerged from these studies was Galectin-3 or LGALS3, which is constitutively expressed at several barrier tissue sites primed to act against pathogens. Identifying mechanisms regulating LGALS3 and its functional role in maintaining epithelial homeostasis and barrier defense could enable us to improve therapeutic strategies for urinary tract infections. The central hypothesis for this study is that LGALS3 expression protects against urinary tract infection by maintaining baseline levels of NF-κB activation in the urethral epithelium.