Lipoxygenase Metabolism, study of 5-oxo-ETE its formation and its receptor. Design and synthesis of photo affinity radiolabelled probes for the characterization of the 5-oxo-ETE receptor.
Synthesis of isoprostanes and the development of methods to measure them in vivo as an index of free radical generation in disease states---novel approach to degenerative diseases (e.g., cardiovascular, Alzheimer, etc).
M.S. The Hebrew University
Ph.D. Weizmann Institute of Science
Dr. Rokach has received worldwide recognition for the first syntheses of major inflammatory mediators such as leukotrienes and lipoxins that are responsible for diseases such as allergies of the lung and nose (asthma, rhinitis) and play a major role in diseases such as inflammatory bowel diseases. The availability of these synthetic mediators has opened the field to medical research in the areas of allergy and inflammation. Dr. Rokach and his team have designed selective drugs in this area that are now on the market as prescription drug for asthma (Singulair). In recognition of his scientific achievements, Dr. Rokach has been awarded several prizes and honors, including the Government of Canada Silver Award (1986); Prix Urgel Archambault (1986); Canadian Society for Chemistry, John Labatt Ltd. Award (1988); Xerox Lecturer (1988); Chinese Academy of Science (Taiwan) Award (1988); and the Paul Ehrlich Prize (Paris, France) (1990).
In addition to his research activities, Dr. Rokach serves on various international advisory committees and on the editorial boards of several scientific journals. He is the author of 243 refereed publications, 40 reviews, 57 patents, and the author and editor of the book Leukotrienes and Lipoxygenases.
"Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid." W. S. Powell and J. Rokach. Biochimica et Biophysica Acta (BBA), 1851, 340-355 (2015).
"Biosynthesis and actions of 5-oxoeicosatetraenoic acid (5-oxo-ETE) on feline granulocytes." C.Cossette, S. Gravel, C. N. Reddy, V. Gore, S. Chourey, Q. Ye, N. W. Snyder, C. A. Mesaros, I. A. Blair, J-P. Lavoie, C. R. Reinero, J. Rokach, and W. S. Powell. Biochemical Pharmacology, 96, 247-255 (2015).
"Two Potent OXE-R Antagonists: Assignment of Stereochemistry." P. Patel, C. N. Reddy,
V. Gore, S. Chourey, Q. Ye, Y. P. Ouedraogo, S. Gravel, W. S. Powell, and J. Rokach. ACS Medicinal Chemistry Letters, 5, 815-819 (2014).
"Base-dependent formation of cis and trans olefins and their application in the synthesis of 5-oxo-ETE receptor antagonists." V. Gore, S. Chourey, Q. Ye, P. Patel, Y. Quedraogo, S. Gravel, W. S. Powell, J. Rokach. Bioorganic & Medicinal Chemistry Letters, 24, 3385-3388 (2014).
"The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor." W. S. Powell, J. Rokach. Prog. Lipid Res., 52, 651-665 (2013).
"5-Oxo-ETE Receptor Antagonists." V. Gore, P. Patel, C. T. Chang, S. Sivendran, N. Kang, Y. P. Quedraogo, S. Gravel, W. S. Powell, J. Rokach. Journal of Medicinal Chemistry, 56, 3725- 3732 (2013).
"C20-trifluoro-5-oxo-ETE: A Metabolically Stable 5-oxo-ETE Derivative." P. Patel, V. Gore, W. S. Powell, and J. Rokach. Bioorganic & Medicinal Chemistry Letters, 21, 1987-1990 (2011).
"Enantio- and stereospecific syntheses of 15(R)-Me-PGD2, A potent and selective DP2-receptor agonist." P. Patel P, G. J. Lee, S. Kim, G. E. Grant, W. S. Powell, and J. Rokach. Journal of Organic Chemistry, 73, 7213-7218 (2008).
"Human neutrophils convert the sebum-derived polyunsaturated fatty acid sebaleic acid to a potent granulocyte chemoattractant." C. Cossette, P. Patel, J. R. Anumolu, S. Sivendran, G. J. Lee, S. Gravel, F. D. Graham, A. Lesimple, O. A. Mamer, J. Rokach, and W. S. Powell. Journal of Biological Chemistry, 283, 11234-11243 (2008).
"Neurofurans: Novel indices of oxidant stress derived from Docosahexaenoic Acid." W. L. Song , J. A. Lawson, D. Reilly, J. Rokach, C. T. Chang, B. Giasson, and G. A. FitzGerald. Journal of Biological Chemistry, 283, 6-16 (2008).
"Reductive deprotection of Silyl Groups with Wilkinson's catalyst/catechol borane." P. Patel, C. T. Chang, N. Kang, G. J. Lee, W. S. Powell, and J. Rokach. Tetrahedron Letters, 48, 5289-5292 (2007).
"Airway epithelial cells synthesize the lipid mediator 5-oxo-ETE in response to oxidative stress." K. R. Erlemann, C. Cossette, S. Gravel, A. Lesimple, G. J. Lee, G. Saha, J. Rokach, and W. S. Powell. Free Radical Biology & Medicine, 42, 654-664 (2007).
"Total synthesis of 8,12-iso-iPF3-VI, an EPA-derived isoprostane: Stereoselective introduction of the fifth asymmetric center." Jacobo SH, Chang CT, Lee GJ, Lawson JA, Powell WS, Pratico D, FitzGerald GA, Rokach J. Journal of Organic Chemistry, 71, 1370-1379 (2006).
"Biochemistry, biology and chemistry of the 5-lipoxygenase product 5-oxo-ETE." Powell WS, Rokach J. Progress in Lipid Research, 44, 154-183 (2005).
"5-Oxo-6,8,11,14-eicosatetraenoic acid stimulates the release of the eosinophil survival factor granulocyte-macrophage colony stimulating factor from monocytes." Stamatiou PB, Chan CC, Monneret G, Ethier D, Rokach J, Powell WS. Journal of Biological Chemistry, 279, 28159-28164 (2004).
"Total synthesis of isoprostanes: Discovery and quantitation in biological systems." Rokach J, Kim S, Bellone S, Lawson JA, Pratic D, Powell WS, FitzGerald GA. Chemistry and Physics of Lipids, 128, 35-56 (2004).
"Vitamin E reduces progression of atherosclerosis in low-density lipoprotein receptor-deficient mice with established vascular lesions." Cyrus T, Yao Y, Rokach J, Tang LX, Pratico D. Circulation, 107, 521-523 (2003).
"The first total synthesis of iPF4-VI and its deuterated analog." Kim S, Lawson JA, Pratic D, FitzGerald GA, Rokach J. Tetrahedron Letters, 43, 2801-2805 (2002).
"Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor." Monneret G, Gravel S, Diamond M, Rokach J, Powell WS. Blood, 98, 1942-1948 (2001).
"Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein E-deficient mice." Cyrus T, Pratic D, Zhao L, Witztum J, Rader D, Rokach J, FitzGerald GA, Funk C. Circulation, 103, 2277-2282 (2001).
"Specific analysis in plasma and urine of 2,3-dinor-5,6-dihydro-isoprostane F2-III, a metabolite of isoprostane F2-III and an oxidation product of -linolenic acid." Burke A, Lawson JA, Meagher EA, Rokach J, FitzGerald GA. Journal of Biological Chemistry, 275, 2499-2504 (2000).
"Quantitative high performance liquid chromatography/tandem mass spectrometric analysis of the four classes of F2-isoprostanes in human urine." Li H, Lawson JA, Reilly M, Adiyaman M, Hwang SW, Rokach J, FitzGerald GA. Proceedings of the National Academy of Sciences USA, 96, 13381-13386 (1999).
"Isoprostanes: Formation, analysis and use as indices of lipid peroxidation in vivo." Lawson JA, Rokach J, FitzGerald GA. Journal of Biological Chemistry, 274, 24441-24444 (1999).
"Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis in ApoE-deficient mice." Pratic D, Tangirala RK, Rader DJ, Rokach J, FitzGerald GA. Nature Medicine, 4, 1189-1192 (1998).
"Diels-Alder approach to isoprostanes. Total synthesis of iPF2-V." Pudukulathan Z, Manna S, Hwang SW, Khanapure SP, Lawson JA, FitzGerald GA, Rokach J. Journal of the American Chemical Society, 120, 11953-11961 (1998).
"IPF2-I: An index of lipid peroxidation in humans." Pratic D, Barry OP, Lawson JA, Adiyaman M, Hwang SW, Khanapure SP, Iuliano L, Rokach J, FitzGerald GA. Proceedings of the National Academy of Sciences USA, 95, 3449-3454 (1998).