Introduction: The most commonly diagnosed and lethal subtype of ovarian cancer is tubo-ovarian, high-grade serous carcinoma (HGSC). While the majority of patients respond well to initial treatment with surgery and chemotherapy, many develop a chemotherapy-resistant recurrence of the disease. Therefore, finding new drugs that can kill HGSC using unique mechanisms is crucial in order to improve patient lives and outcomes. My research project focuses on a class of molecules called glycosylated antitumor ether lipids (GAELs). GAELs are a new class of drugs that we proved are able to kill chemotherapy-resistant HGSC cells. In order to progress to clinical trials, we must show the mechanism as to how GAELs kill cells. The overall goal of my project is to figure out how a specific GAEL called L-Rham kills HGSC cells. Our preliminary data indicates a loss of mitochondrial function induced by reactive oxygen species (ROS) potentially leading to mitophagy. Methods: ROS production and mitochondrial depolarization were measured in L-Rham-treated CaOV3 HGSC cells. Alterations in cellular oxygen consumption were determined using a Seahorse XF Analyzer. Mitophagy was inferred by analysis of proteomic data and visualized using electron microscopy. Results: We determined that L-Rham induces ROS, mitochondrial depolarization and decreased mitochondrial respiration in HGSC cells. I hypothesized that L-Rham initiates ROS-induced loss of mitochondrial function via mitophagy, and preliminary data using electron microscopy appear to confirm this. Ongoing experiments are examining L-Rham effects on glycolysis and TCA cycle, necroptosis as an alternative cell death pathway, and evaluating altered protein expression/localization associated with mitophagy. Conclusion: Collectively, my project will result in a new understanding for how L-Rham (and other GAELs) are effective in killing chemotherapy-resistant HGSC cells. Eventually, this research will allow L-Rham to progress to clinical trials.