Epithelial linings of organs that interface with the environment employ innate immune defenses to protect against environmental exposures and pathogens. Understanding the role of specific immune modulating genes expressed by epithelial barriers will improve our ability to design targeted therapies to prevent chronic inflammation and tissue damage following infection. The lower urinary tract, comprised of the bladder and urethra, acts as a barrier against urine components as well as urinary pathogens originating from the gut. Recent advances in single cell transcriptomics have enabled us to resolve cell type-specific gene expression in the urethra and bladder epithelium, revealing the plethora of immune modulating and defense genes expressed by these epithelial barriers. Although most research has focused on the bladder, a key gap in knowledge is the role of the urethra during urinary tract infections. Urinary pathogens, usually originating in the gut, have to ascend the length of the urethra to infect bladder cells. My previous work showed that urethral cells are not passive onlookers and express antimicrobial peptides, microbial recognition receptors and chemokines. Understanding how immune defenses in the urethra are regulated can potentially allow us to limit infections before they spread to the bladder. The long-term goal of my lab is to understand the regulation of immune modulators and defense genes in the lower urinary tract and harness this knowledge to develop novel therapeutic strategies to treat urinary tract infections that do not rely on antibiotics.