eicosanoids • leukotrienes • prostaglandins • inflammation • asthma
My research focuses on the roles of eicosanoids in inflammation, especially related to asthma. We discovered the 5-lipoxygenase product, 5-oxo-ETE that can by synthesized by both inflammatory and structural cells and is the strongest known chemoattractant for human eosinophils among lipid mediators. We are currently studying the regulation of its biosynthesis and its biological activities and are collaborating with a chemist (Joshua Rokach at the Florida Institute of Technology) to develop 5-oxo-ETE receptor antagonists that could potentially be used for the treatment of asthma and other eosinophilic disorders. We are screening various synthetic compounds and have identified several with nanomolar potencies. We are currently investigating the pharmacokinetics and efficacy of some of these compounds in primate models. Another project we are involved in is the regulation of NADPH oxidase in inflammatory cells. In this case we are investigating the regulation of pyridine nucleotide levels (principally NADPH) in neutrophils.
Powell WS, Rokach J. The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor. Prog Lipid Res. 2013 Sep 19;52(4):651-665. doi: 10.1016/j.plipres.2013.09.001
Gore V, Patel P, Chang CT, Sivendran S, Kang N, Ouedraogo YP, Gravel S, Powell WS, Rokach J. 5-Oxo-ETE receptor antagonists. J Med Chem. 2013 May 9;56(9):3725-32. doi: 10.1021/jm400480j.
Grant GE, Rubino S, Gravel S, Wang X, Patel P, Rokach J, Powell WS. Enhanced formation of 5-oxo-6,8,11,14-eicosatetraenoic acid by cancer cells in response to oxidative stress, docosahexaenoic acid and neutrophil-derived 5-hydroxy-6,8,11,14-eicosatetraenoic acid. Carcinogenesis. 2011 Jun;32(6):822-8. doi: 10.1093/carcin/bgr044.
Grant GE, Gravel S, Guay J, Patel P, Mazer BD, Rokach J, Powell WS. 5-oxo-ETE is a major oxidative stress-induced arachidonate metabolite in B lymphocytes. Free Radic Biol Med. 2011 May 15;50(10):1297-304. doi: 10.1016/j.freeradbiomed.2011.02.010.
Graham FD, Erlemann KR, Gravel S, Rokach J, Powell WS. Oxidative stress-induced changes in pyridine nucleotides and chemoattractant 5-lipoxygenase products in aging neutrophils. Free Radic Biol Med. 2009 Jul 1;47(1):62-71. doi: 10.1016/j.freeradbiomed.2009.04.016.