Research interests Enzymology of prostaglandin synthesis; membrane protein structure and function; mechanisms of non-steroidal anti-inflammatory agents.
My lab's overall objective is to characterize the mechanisms, regulation, and pharmacology of eicosanoid biosynthetic enzymes. The current focus is on prostaglandin H synthase-2, an enzyme with important roles in inflammation, carcinogenesis, wound healing, and reproductive function. This enzyme is regulated by reactive oxygen species, and it is the target of an exciting new class of non-steroidal anti-inflammatory (and potentially anti-carcinogenic) drugs. Our general approach is to use biochemical and biophysical characterization of native enzyme and specific mutants to study the relationships among enzyme structure, catalytic function, and inhibitor action. A tutorial rotation in the lab offers the opportunity to use a variety of molecular, biochemical, spectroscopic, and kinetic techniques to better understand the ways this enzyme's structure influences its participation in health and disease processes.
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Liu W, Rogge CE, Kamensky Y, Tsai AL, Kulmacz RJ (2007) Protein Expr Purif, in press. Development of a bacterial system for high yield expression of fully functional adrenal cytochrome b(561).
Poole EM, Bigler J, Whitton J, Sibert JG, Kulmacz RJ, Potter JD, Ulrich CM (2007) Carcinogenesis 28, 1259-1263. Genetic variability in prostaglandin synthesis, fish intake, and risk of colorectal polyps.
Wu G, Rogge CE, Wang JS, Kulmacz RJ, Palmer G, Tsai AL (2007) Biochemistry 46, 534-542. Oxyferryl heme and not tyrosyl radical is the likely culprit in prostaglandin H synthase-1 peroxidase inactivation.
Liu W, Wang LH, Fabian P, Hayashi Y, McGinley CM, van der Donk WA, Kulmacz RJ (2006) Plant Physiol Biochem 44, 284-293. Arabidopsis thaliana fatty acid alpha-dioxygenase-1: evaluation of substrates, inhibitors and amino-terminal function.
Liu W, Cao D, Oh SF, Serhan CN, Kulmacz RJ (2006) FASEB J 20, 1097-1108. Divergent cyclooxygenase responses to fatty acid structure and peroxide levels in fish and mammalian prostaglandin H synthases.
Rogge CE, Ho B, Liu W, Kulmacz RJ, Tsai A-L (2006) Biochemistry 45, 523-532. Role of Tyr348 in Tyr385 radical dynamics and cyclooxygenase inhibitor interactions in prostaglandin H synthase-2.
Liu W, Rogge CE, Bambai B, Palmer G, Tsai AL, Kulmacz RJ (2004) J Biol Chem 279, 29805-29815. Characterization of the heme environment in Arabidopsis thaliana fatty acid alpha-dioxygenase-1
Rogge CE, Liu W, Wu G, Kulmacz RJ, Tsai A-L (2004) Biochemistry 43, 1560-1568. Identification of Tyr504 as an alternative tyrosyl radical site in human prostaglandin H synthase-2. Bambai B, Rogge CE, Stec B., Kulmacz RJ (2004) J Biol Chem 279, 4084-4092. Role of Asn382 and Thr383 in activation and inactivation of human prostaglandin H synthase cyclooxygenase catalysis.
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Department of Internal Medicine, Hematology