Biosynthesis of Oxygenated Lipid Signaling Molecules

Eicosanoids are potent cellular signaling molecules derived from polyunsaturated fatty acids. They include prostaglandins, leukotrienes, hydroxy fatty acids, and epoxy fatty acids. Eicosanoids have been implicated in a wide variety of patho-physiological processes, including carcinogenesis, hemostasis, inflammation, renal function, reproduction, and sleep/wake cycles. My general goal is to understand at the molecular level how eicosanoid biosynthesis is accomplished and regulated.

A major control point in eicosanoid biosynthesis is the initial formation of a lipid hydroperoxide, catalyzed by one of several fatty acid oxygenases. My lab's current focus is on prostaglandin H synthase, which catalyzes the initial step in the synthesis of all prostaglandins. There are two isoforms of the synthase, with distinct physiological functions and distinct catalytic regulation. We are interested in relating catalytic differences between the isoforms to specific mechanistic and structural differences.