Our laboratory's research examines the role of lipid mediators (eicosanoids) in human health and disease. The work is translational in nature and utilizes state-of-the-art analytical methodologies to study mechanisms of oxidative and inflammatory injury. This research contributes to our understanding of how oxidant stress and inflammation impact human physiological and pathophysiological processes. The major effort of our research concerns the biochemistry and pharmacology of a novel group of oxidized arachidonic acid species termed isoprostanes. The importance of this work is that the isoprostanes exert potent biological activity and thus likely mediate some of the adverse effects associated with oxidant stress and inflammation. Further, the isoprostanes represent the most accurate method to assess oxidative stress status in vivo in humans and have revolutionalized our ability to examine the role of oxidant injury in disease processes. Studies regarding these compounds evolved from a discovery that the laboratory made in the early 1990's in which it reported that bioactive prostaglandin F2-like compounds, now termed F2-isoprostanes, are produced in large amounts in vivo in humans from the free radical-initiated peroxidation of arachidonic acid independent of the cyclooxygenase enzyme (see figure). Subsequent experiments advanced our understanding of mechanisms involved in the formation and metabolism of these novel compounds, in particular that unlike cyclooxygenase-derived prostaglandins in which arachidonic acid must be hydrolyzed from a phospholipid storage site prior to oxygenation, the isoprostanes are formed in situ esterified in lipids and are subsequently released by the action of phospholipase A2. Thus, unlike prostaglandins, the isoprostanes can exist in a preformed, sequestered state. Additional studies carried out in our laboratory identified other products of the isoprostane pathway including compounds containing D/E-type, A/J-type, and thromboxane-like ring structures and determined that various conditions modulate the distribution of isoprostane products formed in vivo in humans. There are a number of varied basic and translational research projects ongoing in the laboratory to examine the formation, metabolism, and biological actions of the isoprostanes and related compounds.