Ether lipids are critical regulators of membrane structure, redox balance, and signaling pathways that are frequently dysregulated in cancer. Recent work has identified ACAD10 as a key enzyme in ether lipid biosynthesis and salvage, where it catalyzes essential phosphorylation and dephosphorylation steps required to maintain cellular ether lipid pools. This project aims to investigate the functional consequences of ACAD10 knockdown in cancer cells to determine how loss of ACAD10 alters ether and ester lipid synthesis pathway, cellular adaptation to lipid overload, and cancer cell survival Using genetic knockdown approaches, an ACAD10-deficient cell line will be generated and assessed for changes in ether-lipid-dependent processes, including plasmalogen synthesis, peroxisomal and ER-dependent lipid handling, and metabolic adaptation to lipid challenge. In addition, a cell line deficient in ACAD11, a potential paralog of ACAD10, will be generated as a control. Molecular assays such as cell cloning, DNA and RNA isolation, qPCR, and Western blotting will be used to confirm knockdown efficiency and characterize downstream transcriptional and protein level changes. These analyses will be complemented by studies examining how ACAD10 loss impacts lipid metabolic pathways that may be selectively exploited in cancer cells. By linking ACAD10 mediated ether lipid metabolism to cancer cell function, this work seeks to clarify how metabolic vulnerabilities in ether lipid pathways can be leveraged for targeted cancer therapies.
Northeastern University
