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.
Rogge CE, Liu W, Kulmacz RJ, Tsai AL. Peroxide-induced radical formation at TYR385 and TYR504 in human PGHS-1. J Inorg Biochem. 103:912-922, 2009.
Liu W, Rogge CE, da Silva GF, Shinkarev VP, Tsai AL, Kamensky Y, Palmer G, Kulmacz RJ. His92 and His110 selectively affect different heme centers of adrenal cytochrome b(561). Biochim Biophys Acta. 1777:1218-1228, 2008.
Rand Doyen J, Yucer N, Lichtenberger LM, Kulmacz RJ. Phospholipid actions on PGHS-1 and -2 cyclooxygenase kinetics. Prostaglandins Other Lipid Mediat. 85:134-143, 2008.
Kamensky Y, Liu W, Tsai AL, Kulmacz RJ, Palmer G. Axial ligation and stoichiometry of heme centers in adrenal cytochrome b561. Biochemistry. 46:8647-8658, 2007.
Liu W, Rogge CE, Kamensky Y, Tsai AL, Kulmacz RJ. Development of a bacterial system for high yield expression of fully functional adrenal cytochrome b(561). Protein Expr Purif, 56:145-152, 2007.
Poole EM, Bigler J, Whitton J, Sibert JG, Kulmacz RJ, Potter JD, Ulrich CM Genetic variability in prostaglandin synthesis, fish intake, and risk of colorectal polyps Carcinogenesis 28, 1259-1263, 2007.
Wu G, Rogge CE, Wang JS, Kulmacz RJ, Palmer G, Tsai AL Oxyferryl heme and not tyrosyl radical is the likely culprit in prostaglandin H synthase-1 peroxidase inactivation. Biochemistry 46, 534-542., 2007.
Liu W, Wang LH, Fabian P, Hayashi Y, McGinley CM, van der Donk WA, Kulmacz RJ Arabidopsis thaliana fatty acid alpha-dioxygenase-1: evaluation of substrates, inhibitors and amino-terminal function. Plant Physiol Biochem 44, 284-293, 2006.
Liu W, Cao D, Oh SF, Serhan CN, Kulmacz RJ Divergent cyclooxygenase responses to fatty acid structure and peroxide levels in fish and mammalian prostaglandin H synthases. FASEB J 20, 1097-1108, 2006.
Rogge CE, Ho B, Liu W, Kulmacz RJ, Tsai A-L Role of Tyr348 in Tyr385 radical dynamics and cyclooxygenase inhibitor interactions in prostaglandin H synthase-2. Biochemistry 45, 523-532, 2006.
Search PubMed for a complete list of Dr. Kulmacz's publications.