Leveraging Organoid Models to Study Candida-Host Interactions and Candidalysin-Dependent Damage in Vulvovaginal and Systemic Candidiasis.dissertationsKhalil, Aseel Khalil HusseincreatorBennett, RichardAdvisorJamieson, AmandaReaderVaishnava, ShipraReaderBrown University. Biology and Medicine: Biotechnologysponsor2025, 45 p.born digitalThesis (Sc. M.)--Brown University, 2025thesesGiven the widespread nature of vulvovaginal candidiasis, understanding the molecular mechanisms underlying its pathogenesis and systemic spread could inform therapeutic development. This study uses vaginal and colon epithelial organoid models to assess transcriptional and inflammatory responses of mammalian hosts to Candida albicans and its secreted toxin, candidalysin. Due to the limitations of three-dimensional organoids in examining infectious disease, we optimize their use for the study of Candida-host interactions by generating vaginal epithelial organoid-derived monolayers. RNA-seq analysis reveals an upregulation in hypoxic-stress that was corroborated by a perturbation of oxygen consumption rates following infection with C. albicans within the vaginal epithelia. Through a variety of in vitro cell viability assays, we show that candidalysin facilities adhesion, cell death, and can compromise barrier integrity. This data highlights the potential translational role of Candidalysin as a therapeutic target in the treatment of candidiasis and the appeal of organoid models in identifying novel respiration-related phenotypes.Biologyinfectious diseaseEnglishRPB20250707