Numerous signal transduction processes involve lipids as signaling molecules. Many of these molecules are generated by phospholipases such as phospholipase A2, which releases fatty acids like arachidonic acid, and lysophospholipids. Each of these products is implicated in signal transduction processes, but also serves as a precursor for platelet activating factor or the eicosanoids. The eicosanoids are a large family of bioactive mediators that derive from the enzymatic oxygenation of arachidonic acid. Prostaglandins, leukotrienes, thromboxane, lipoxins, are all members of the eicosanoid family. The eicosanoids are biomedically important because they mediate all four signs of inflammation, namely heat, redness, swelling and pain. Controlling the formation of eicosanoids has been found to be of great benefit for the treatment of acute and chronic inflammatory diseases. 

Lipid signaling is also key to the development of diabetes and the myriad of metabolic diseases associated to it (e.g. obesity, metabolic syndrome, cardiovascular disease, etc). Of note, many of the enzymes involved in glycerolipid biosynthetic pathways may act to initiate intracellular signaling.

While our long-term goals include all kinds of enzymes potentially involved in lipid signaling, our current research focuses primarily on phospholipase A2 and phosphatidate phosphohydrolase (phosphatidic acid-specific phospholipase C; lipin). General events that we are interested in include (i) the spatiotemporal regulation of these phospholipases in a cellular context, which we study utilizing advanced microscopy techniques, (ii) pharmacological manipulation of enzymatic activity both in intact cells and in vitro, (iii) analysis of lipid metabolite production by state-of-the-art mass spectrometry (lipidomics & metabolipidomics), and (iv) the physiological functioning of phospholipases in animal models.

Ongoing studies are focusing on the localization and stimulus-driven translocation of  different members of the phospholipase A2 and lipin families. Phospholipase A2s cleave the fatty acid at the sn-2 position of phospholipids and thus constitute the earliest regulatory point of the eicosanoid biosynthetic cascade. Lipins dephosphorylate phosphatidic acid to form diacylglycerol, which is used for the biosynthesis of glycerophospholipids and triacylglycerol. Current studies are being carried out by transfecting chimeric constructs of green fluorescent protein (GFP) (or any of its colored varieties) with the appropriate phospholipase. GFP is placed at either the N- or C-termini. of the enzymes. These constructs provide a very useful tool to visualize the intracellular movements of the enzymes in response to the different stimuli. Mutagenesis studies are also being conducted to pinpoint the specific amino acids of the phospholipase A2s and lipins that are implicated in the movement among intracellular compartments.