Sarah Speck
Program: Molecular Cell Biology
Current advisor: Clay F. Semenkovich, MD
Undergraduate university: Washington University
Research summary
The mechanism of how fatty acids regulate diabetes and insulin resistance is not yet clear. Fatty acids can covalently modify proteins, regulating protein stability, function, and localization through a reversible process known as palmitoylation. However, the role of depalmitoylation in glucose metabolism is uncertain. Given the importance of the liver in systemic glucose metabolism and storage, I chose to study two depalmitoylases in the liver: acyl-protein thioesterase 1 (APT1) and acyl-protein thioesterase 2 (APT2). I hypothesized that depalmitoylation by both hepatic APT1 and APT2 is important for regulating hepatic glucose metabolism. To determine if APT1 and APT2 have functional redundancy, I first aim to identify the interacting proteins of both enzymes in vitro. For my second aim, I am investigating the combined effect of APT1 and APT2 deficiency on murine hepatic glucose metabolism. These studies have the potential to implicate reversible lipid modifications in the progression of metabolic disease.
Graduate publications
Dong G, Adak S, Spyropoulos G, Zhang Q, Feng C, Yin L, Speck SL, Shyr Z, Morikawa S, Kitamura RA, Kathayat RS, Dickinson BC, Ng XW, Piston DW, Urano F, Remedi MS, Wei X, Semenkovich CF. 2023 Palmitoylation couples insulin hypersecretion with β cell failure in diabetes. Cell Metab, 35(2):332-344.e7.
Wei X, Adak S, Zayed M, Yin L, Feng C, Speck SL, Kathayat RS, Zhang Q, Dickinson BC, Semenkovich C. 2020 Endothelial Palmitoylation Cycling Coordinates Vessel Remodeling in Peripheral Artery Disease. Circ Res, 127(2):249-65.