Oxidative Cell Death
Oxidation of the lipids that comprise our cell membranes, as well as the membranes of the various organelles and components of our cells, has long been implicated in the pathogenesis of a wide variety of degenerative diseases, as well as cancer and aging. To better understand the part lipid oxidation products play in these processes, we study the mechanisms by which lipids oxidize, as well as the mechanisms by which the oxidation products interact with other cellular constituents. Moreover, we synthesize what we believe to be particularly relevant oxidation products, and/or specifically-derivatized versions thereof, in order to probe their roles in cell and animal models of disease. Lipid classes currently under active investigation in the laboratory include plasmalogens, sterols and polyunsaturated fatty acids. Researchers pursuing projects in this area train in organic synthesis and kinetic and mechanistic studies, and may gain additional experience in the analysis of cell and tissue extracts with state-of-the-art UPLC with tandem mass spectrometry, molecular and cell biology, and cell imaging.
For more info, please check out some of our recent work in this area:
The Chemical Basis of Ferroptosis
Marcus Conrad* & Derek A. Pratt* Nature Chemical Biology 2019, 15, 1137-1147.
FSP1 is a Glutathione-Independent Ferroptosis Suppressor
Doll et al. Nature 2019, 575, 693-698.
Beyond DPPH: Use of Fluorescence-ENabled Inhibited AutoXidation (FENIX)
Predicts Oxidative Cell Death Rescue
Ron Shah, Luke A. Farmer, Omkar Zilka, Antonius T. M. Van Kessel & Derek A. Pratt*
Cell Chemical Biology 2019, 26, 1594-1607.
Resolving the Role of Lipoxygenases in the Initiation and Execution of Ferroptosis
Ron Shah, Mikhail S. Shchepinov & Derek A. Pratt*
ACS Central Science 2018, 4, 387-396.
On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death
Omkar Zilka, Ron Shah, Bo Li, José Pedro Friedmann Angeli, Markus Griesser, Marcus Conrad & Derek A. Pratt*
ACS Central Science 2017, 3, 232-243.