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Edward Dennis, Ph.D.
Dr. Dennis’s work has focused on understanding the regulation of lipid mediators and particularly the role of cytosolic, secreted, and membrane-bound phospholipase A2s (PLA2) in macrophages. His ongoing aim is to characterize the regulatory mechanisms of these phospholipase A2s both in vitro and in the intact cell. His work has led to development of in vitro systems for studying their detailed mechanism of action. PLA2s have multiple phospholipid binding motifs (activator sites, interfacial sites, and catalytic sites) and it important to define the amino acid residues involved in these actions. The Dennis group is carrying out site-directed mutagenesis on various PLA2s derived from human genes and mass spectrometric analysis of surface interactions. In addition to their work on lipase structure and function, they have also been involved in the design and synthesis of phospholipase A2 inhibitors. Trainees could participate in any of these activities.
Selected Publications
Buczynski MW, Stephens DL, Bowers-Gentry RC, Grkovich A, Deems RA, Dennis EA. TLR-4 and sustained calcium agonists synergistically produce eicosanoids independent of protein synthesis in RAW264.7 cells. J Biol Chem 282:22834-22837, 2007.
Harkewicz R, Fahy E, Andreyev A, Dennis EA. Arachidonate-derived dihomoprostaglandin production observed in endotoxin-stimulated macrophage-like cells. J Biol Chem 282:2899-2910, 2007.
Grkovich A, Johnson CA, Buczynski MW, Dennis EA. Lipopolysaccharide-induced cyclooxygenase-2 expression in human U937 macrophages is phosphatidic acid phosphohydrolase-1-dependent. J Biol Chem 281:32978-32987, 2006
Winstead MV, Lucas KK, Dennis EA. Group IV cytosolic phospholipase A2 mediates arachidonic acid release in H9c2 rat cardiomyocyte cells in response to hydrogen peroxide. Prostaglandins Other Lipid Mediat 78:55-66, 2005.