ur laboratory explores biochemical mechanisms of lipid second messenger production. We are enthusiastic participants in two NIGMS large scale collaborative projects: (1) The Alliance for Cellular Signaling and (2) LIPID MAPS. We use ESI - Mass Spectrometry to detect and analyze lipid changes and define cell signaling pathways in the macrophage. Our group has developed a technology called Lipid Arrays that permits a lipidomic analysis of changes in membrane phospholipid content during cell signaling events and characterize disease states as well as other cellular processes. The group is highly interdisciplinary and includes researchers with backgrounds in analytical and organic chemistry, mathematics, theoretical physics, biochemistry, cell biology, and pharmacology. We also are focused on understanding membrane responses to intracellular signals (such as hormones and neurotransmitters) that generate bioactive lipid signals. A current focus is on receptor - mediated regulation of monomeric G proteins, such as ADP-ribosylation factor (Arf), Cdc42, and protein kinase C to activate phospholipase D (PLD) in cells. The hydrolysis of phosphatidycholine by PLD alters the biophysical properties of the lipid bilayer and may play key roles in processes that require membrane remodeling (e.g. degranulation, vesicle biogenesis, cytoskeletal organization, and control of cell proliferation). We are especially interested in the role of G protein-regulated phospholipases in cell transformation and metastasis. With our colleagues at the Vanderbilt-Ingram Cancer Center we have begun a long term effort to profile lipid changes in cancer cells for the purpose of understanding the molecular changes that transform normal cells into tumors and whether these changes can be exploited for molecular therapies. Another major interest in the laboratory includes understanding the role lipids play in regulated exocytosis. Mast cells and macrophages are used to study regulated changes in membrane lipid composition and the role of these changes in membrane fusion and vesicular content release.