Department of Biochemistry

My research deals with the role of fatty acids and their derivatives in biological systems. I am most interested in polyunsaturated fatty acids because they are substrates for the synthesis of bioactive lipid mediators. My laboratory is currently investigating four questions regarding polyunsaturated fatty acids.

The first involves the function of epoxyeicosatrienoic acids (EETs), arachidonic acid epoxide derivatives synthesized by cytochrome P450 epoxygenases. EETs are vasodilators that act on membrane ion channels. These lipid biomediators are incorporated into the phospholipids, including phosphatidylcholine and phosphatidylinositol, in endothelial and smooth muscle cells. My hypothesis is that EETs may affect the function of blood vessels, and possibly protect against vascular diseases, by modulating paracrine or autacrine signal transduction processes in the vascular wall. Endothelial and smooth muscle cells also convert EETs to dihydroxy derivatives called dihydroxyeicosatrienoic acids (DHETs). We are exploring the effects of DHETs to determine whether they also have bioactive properties.

A related question concerns how inhibitors of soluble epoxide hydrolase, the enzyme that converts EETs to DHETs, affects the metabolism and properties of EETs in cells that regulate cardiovascular function. We have detected the formation of several novel EET metabolites in endothelial cells when soluble epoxide hydrolase is inhibited, and the bioactivity of these products is being explored. These effects have been observed so far in cell cultures, and we are in the process of determining whether selective soluble epoxide hydrolase inhibitors produce similar effects in human vascular tissue.