Darryl C. Zeldin, MD, National Institute of Environmental Health Sciences/NIH

The research focus in the Zeldin group is P450- and cyclooxygenase-derived eicosanoids, with an emphasis on how they function in the respiratory and cardiovascular systems. Their group has identified a number of P450s that are active in the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs) in the respiratory and cardiovascular systems. They have also shown that soluble epoxide hydrolase (sEH) is the main enzyme involved in EET removal. EETs possess a myriad of biological effects and are involved in the regulation of vascular and airway tone, inflammation, and response to environmental stressors such as ischemia. Opportunities for translational research in this area include development of novel therapeutics for management of hypertension, atherosclerosis, ischemic heart disease and inflammatory diseases of the lung. The cyclooxygenase work focuses on the role of prostaglandins in regulating lung function under both normal and pathological conditions. Work in this area is based on the hypothesis that cyclooxygenase-derived eicosanoids are important modulators of the lung immune response to environmental agents such as allergens, respiratory viruses and bacterial lipopolysaccharide. The group has utilized cyclooxygenase knockout mice and developed cyclooxygenase transgenic animals to study the effects of altered prostaglandin biosynthesis in the lung. The studies in this area will lead to additional opportunities for both mechanistic and translational research in environmental lung diseases.