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H. Alex Brown, Ph.D.,
Our 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 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 or other cellular processes. The group is highly interdisciplinary and includes researchers with backgrounds in analytical and organic chemistry, mathematics, and pharmacology. We also are focused on understanding membrane responses to intracellular signals (such as hormones and neurotransmitters) that generate bioactive lipid signals. One important example is the enzyme phospholipase D (PLD), which catalyzes the production of phosphatidic acid and subsequently other biologically active lipids. The current focus is on receptor-mediated regulation of monomeric G proteins, such as ADP-ribosylation factor (Arf) and Cdc42, and protein kinase C to activate PLD in cells. Several techniques and approaches (e.g., protein purification and reconstitution, lipid analysis by LC-MS, Electron spin resonance analysis of lipid bilayers, and determination of protein structures) are utilized to pursue questions on phospholipase regulation and function. The hydrolysis of phosphatidylcholine 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 as well as diseases that involve immune and allergic processes. Counting fats: new consortium to map cellular lipids - VMC Reporter article September 26, 2003 |
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