Biomedical Research Education & Training
Faculty Member

Schneider, Claus, Ph.D.
Associate Professor of Pharmacology

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Phone Number: 615-343-9539

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Schneider, Claus's picture
Academic history
B.A., Univ of Wurzburg, Germany
MS, Univ of Wurzburg, Germany
Ph.D., Univ of Wurzburg, Germany

Office Address   Mailing Address

514 RRB

514 RRB 6602

Research Keywords
lipid signaling, lipid hormones, cyclooxygenase, lipoxygenase, mechanism, chemoprevention, structure-function, prostaglandin, leukotriene, curcumin, stereochemistry, lipid peroxidation, subcellular localization, structural biology, biochemistry, enzyme action, mass spectrometry, mutation, NMR, protein structure, spectroscopy, structural biology

Research Specialty
Discovery and characterization of novel lipid mediators. Mechanisms of oxygenation of fatty acids. Chemopreventive activity of curcumin.

Research Description
We are studying the biochemistry of lipid signaling. We are interested in how lipid signaling hormones are formed and what their roles are in human health and disease.

1. Discovery and characterization of novel lipid mediators
The cyclooxygenase and lipoxygenase enzymes catalyze the first step in the formation of a diverse array of lipid mediators (?eicosanoids?) from arachidonic acid. We are interested in exploring novel pathways of how these mediators are formed, and to establish their role in the progression of inflammatory diseases like atherosclerosis or cancer.

2. Mechanisms of oxygenation of fatty acids
Lipid peroxidation and oxidative stress are elementary pathophysiological processes involved in the progression of many diseases, e.g., atherosclerosis, Alzheimer's, and cardiovascular diseases. The lipid aldehyde, 4-hydroxynonenal (HNE), has been recognized as one of the most cytotoxic products formed during lipid peroxidation almost three decades ago. Yet despite the wealth of information on its pathological properties, only little is known about its mechanism(s) of formation. We are using model autoxidation reactions with common and unusual fatty acid hydroperoxide precursors to identify mechanistically significant intermediates that shed a light on the pathways of formation of HNE. The products are analyzed using LC-MS, NMR, GC-MS, UV, and CD spectroscopy. Part of this research is carried out in collaboration with Ned Porters group in the Department of Chemistry.

3. Curcumin as a chemopreventive agent
Curcumin is the spice that gives curry its yellow color. It has also been used in traditional Asian medicine as an anti-inflammatory and wound-healing agent. In the past few years, curcumin has received increasing attention for use as a dietary cancer chemopreventive agent. We are studying the oxidative metabolism of curcumin, and we are testing the hypothesis that oxidative metabolites of curcumin are contributing to its chemopreventive activity.

Orlando, BJ, McDougle, DR, Lucido, MJ, Eng, ET, Graham, LA, Schneider, C, Stokes, DL, Das, A, Malkowski, MG. Cyclooxygenase-2 catalysis and inhibition in lipid bilayer nanodiscs. Arch Biochem Biophys, 2014

Brash, AR, Boeglin, WE, Stec, DF, Voehler, M, Schneider, C, Cha, JK. Isolation and characterization of two geometric allene oxide isomers synthesized from 9S-hydroperoxylinoleic acid by cytochrome P450 CYP74C3: stereochemical assignment of natural fatty acid allene oxides. J Biol Chem, 288(29), 20797-806, 2013

Gordon, ON, Graham, LA, Schneider, C. Facile synthesis of deuterated and [(14) C]labeled analogs of vanillin and curcumin for use as mechanistic and analytical tools. J Labelled Comp Radiopharm, 56(14), 696-9, 2013

Ketron, AC, Gordon, ON, Schneider, C, Osheroff, N. Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases. Biochemistry, 52(1), 221-7, 2013

Brash, AR, Schneider, C, Hamberg, M. Applications of Stereospecifically-Labeled Fatty Acids in Oxygenase and Desaturase Biochemistry. Lipids, 47, 101-116, 2012 PMCID:3243484

Gordon, ON, Schneider, C. Vanillin and ferulic acid: not the major degradation products of curcumin. Trends Molec. Med., 18, 361-363, 2012

McElroy, SJ, Hobbs, S, Kallen, M, Tejera, N, Rosen, MJ, Grishin, A, Matta, P, Schneider, C, Upperman, J, Ford, H, Polk, DB, Weitkamp, JH. Transactivation of EGFR by LPS induces COX-2 expression in enterocytes. PLoS One, 7(5), e38373, 2012

Tejera, N, Boeglin, WE, Suzuki, T, Schneider, C. COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes. J Lipid Res, 53(1), 87-94, 2012 PMCID:3243484

Griesser, M, Pistis, V, Suzuki, T, Tejera, N, Pratt, DA, Schneider, C. Autoxidative and cyclooxygenase-2 catalyzed transformation of the dietary chemopreventive agent curcumin. J Biol Chem, 286(2), 1114-24, 2011

Griesser, M, Suzuki, T, Tejera, N, Mont, S, Boeglin, WE, Pozzi, A, Schneider, C. Biosynthesis of hemiketal eicosanoids by cross-over of the 5-lipoxygenase and cyclooxygenase-2 pathways. Proc Natl Acad Sci U S A, 108(17), 6945-50, 2011

Lee, SH, Schneider, C, Higdon, AN, Darley-Usmar, VM, Chung, CY. Role of iPLA(2) in the Regulation of Src Trafficking and Microglia Chemotaxis. Traffic, 2011

Liu, W, Porter, NA, Schneider, C, Brash, AR, Yin, H. Formation of 4-hydroxynonenal from cardiolipin oxidation: Intramolecular peroxyl radical addition and decomposition. Free Radic Biol Med, 50(1), 166-78, 2011

Schneider, C, Pozzi, A. Cyclooxygenases and lipoxygenases in cancer. Cancer Metastasis Rev, 30(3-4), 277-94, 2011 PMCID:3243484

Mulugeta, S, Suzuki, T, Tejera Hernandez, N, Griesser, M, Boeglin, WE, Schneider, C. Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2. J Lipid Res, 51(3), 575-585, 2010

Gao, B, Boeglin, WE, Zheng, Y, Schneider, C, Brash, AR. Evidence for an ionic intermediate in the transformation of fatty acid hydroperoxide by a catalase-related allene oxide synthase from the Cyanobacterium Acaryochloris marina. J Biol Chem, 284(33), 22087-98, 2009

Griesser, M, Boeglin, WE, Suzuki, T, Schneider, C. Convergence of the 5-LOX and COX-2 pathways: heme-catalyzed cleavage of the 5S-HETE-derived di-endoperoxide into aldehyde fragments. J Lipid Res, 50(12), 2455-62, 2009

Niisuke, K, Boeglin, WE, Murray, JJ, Schneider, C, Brash, AR. Biosynthesis of a linoleic acid allylic epoxide: mechanistic comparison with its chemical synthesis and leukotriene A biosynthesis. J Lipid Res, 50(7), 1448-55, 2009 PMCID:2694342

Schneider, C. An update on products and mechanisms of lipid peroxidation. Mol Nutr Food Res, 53(3), 315-21, 2009

Schneider, C. Books: Nutrition and Arthritis. Edited by Margaret Rayman and Alison Callaghan. Mol Nutr Food Res, 52(4), 502, 2008

Schneider, C, Boeglin, WE, Yin, H, Porter, NA, Brash, AR. Intermolecular Peroxyl Radical Reactions during Autoxidation of Hydroxy and Hydroperoxy Arachidonic Acids Generate a Novel Series of Epoxidized Products. Chem Res Toxicol, 21(4), 895-903, 2008

Schneider, C, Porter, NA, Brash, AR. Routes to 4-hydroxynonenal: Fundamental issues in the mechanisms of lipid peroxidation. J Biol Chem, 283(23), 15539-15543, 2008 PMCID:2414272

Zheng, Y, Boeglin, WE, Schneider, C, Brash, AR. A 49-kDa mini-lipoxygenase from Anabaena sp. PCC 7120 retains catalytically complete functionality. J Biol Chem, 283(8), 5138-47, 2008

Brash, AR, Yu, Z, Boeglin, WE, Schneider, C. The hepoxilin connection in the epidermis. FEBS J, 274(14), 3494-502, 2007

Schneider, C. Book news: stress, obesity, and metabolic syndrome. Edited by George P. Chrousos and Constantine Tsigos. Mol Nutr Food Res, 51(12), 1554, 2007

Schneider, C, Niisuke, K, Boeglin, WE, Voehler, M, Stec, DF, Porter, NA, Brash, AR. Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120. Proc Natl Acad Sci U S A, 104(48), 18941-5, 2007 PMCID:2141887

Schneider, C, Pratt, DA, Porter, NA, Brash, AR. Control of oxygenation in lipoxygenase and cyclooxygenase catalysis. Chem Biol, 14(5), 473-88, 2007 PMCID:2692746

Schneider, C, Yu, Z, Boeglin, WE, Zheng, Y, Brash, AR. Enantiomeric separation of hydroxy and hydroperoxy eicosanoids by chiral column chromatography. Methods Enzymol, 433, 145-57, 2007

Yu, Z, Schneider, C, Boeglin, WE, Brash, AR. Epidermal Lipoxygenase Products of the Hepoxilin Pathway Selectively Activate the Nuclear Receptor PPARalpha. Lipids, 42(6), 491-7, 2007

Furse, KE, Pratt, DA, Schneider, C, Brash, AR, Porter, NA, Lybrand, TP. Molecular Dynamics Simulations of Arachidonic Acid-Derived Pentadienyl Radical Intermediate Complexes with COX-1 and COX-2: Insights into Oxygenation Regio- and Stereoselectivity. Biochemistry, 45(10), 3206-18, 2006 PMCID:2504531

Schneider, C, Boeglin, WE, Yin, H, Stec, DF, Voehler, M. Convergent oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2. J Am Chem Soc, 128(3), 720-1, 2006 PMCID:2532595

Yu, Z, Schneider, C, Boeglin, WE, Brash, AR. Human and mouse eLOX3 have distinct substrate specificities: implications for their linkage with lipoxygenases in skin. Arch Biochem Biophys, 455(2), 188-96, 2006 PMCID:2636205

Chang, MS, Schneider, C, Roberts, RL, Shappell, SB, Haselton, FR, Boeglin, WE, Brash, AR. Detection and subcellular localization of two 15S-lipoxygenases in human cornea. Invest Ophthalmol Vis Sci, 46(3), 849-56, 2005

Coffa, G, Imber, AN, Maguire, BC, Laxmikanthan, G, Schneider, C, Gaffney, BJ, Brash, AR. On the Relationships of Substrate Orientation, Hydrogen Abstraction, and Product Stereochemistry in Single and Double Dioxygenations by Soybean Lipoxygenase-1 and Its Ala542Gly Mutant. J Biol Chem, 280(46), 38756-38766, 2005 PMCID:1351262

Coffa, G, Schneider, C, Brash, AR. A comprehensive model of positional and stereo control in lipoxygenases. Biochem Biophys Res Commun, 338(1), 87-92, 2005

Schneider, C, Boeglin, WE, Yin, H, Ste, DF, Hachey, DL, Porter, NA, Brash, AR. Synthesis of dihydroperoxides of linoleic and linolenic acids and studies on their transformation to 4-hydroperoxynonenal. Lipids, 40(11), 1155-62, 2005

Schneider, Claus. Chemistry and biology of vitamin E. Mol Nutr Food Res, 49(1), 7-30, 2005

Schneider, Claus, Boeglin, William E, Brash, Alan R. Human cyclo-oxygenase-1 and an alternative splice variant: contrasts in expression of mRNA, protein and catalytic activities. Biochem J, 385(Pt 1), 57-64, 2005 PMCID:1134673

Yu, Zheyong, Schneider, Claus, Boeglin, William E, Brash, Alan R. Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3. Biochim Biophys Acta, 1686 3, 238-47, 2005

Schneider, Claus, Boeglin, William E, Brash, Alan R. Identification of two cyclooxygenase active site residues, Leucine 384 and Glycine 526, that control carbon ring cyclization in prostaglandin biosynthesis. J Biol Chem, 279(6), 4404-14, 2004

Schneider, Claus, Porter, Ned A, Brash, Alan R. Autoxidative transformation of chiral omega6 hydroxy linoleic and arachidonic acids to chiral 4-hydroxy-2E-nonenal. Chem Res Toxicol, 17(7), 937-41, 2004

Schneider, Claus, Strayhorn, W David, Brantley, Dana M, Nanney, Lillian B, Yull, Fiona E, Brash, Alan R. Upregulation of 8-lipoxygenase in the dermatitis of IkappaB-alpha-deficient mice. J Invest Dermatol, 122(3), 691-8, 2004

Valmsen, Karin, Boeglin, William E, Jarving, Ivar, Schneider, Claus, Varvas, Kulliki, Brash, Alan R, Samel, Nigulas. Structural and functional comparison of 15S- and 15R-specific cyclooxygenases from the coral Plexaura homomalla. Eur J Biochem, 271(17), 3533-8, 2004

West, James D, Ji, Chuan, Duncan, Stephen T, Amarnath, Venkataraman, Schneider, Claus, Rizzo, Carmelo J, Brash, Alan R, Marnett, Lawrence J. Induction of Apoptosis in Colorectal Carcinoma Cells Treated with 4-Hydroxy-2-nonenal and Structurally Related Aldehydic Products of Lipid Peroxidation. Chem Res Toxicol, 17(4), 453-62, 2004

Brash, Alan R., Jisaka, Mitsuo, Boeglin, William E., Schneider, Claus. On the basis for the positional specificity and stereo specificity of lipoxygenases. Int. Congress Series, 1233, 297-305, 2003

Yu, Zheyong, Schneider, Claus, Boeglin, William E, Marnett, Lawrence J, Brash, Alan R. The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase. Proc Natl Acad Sci U S A, 100(16), 9162-7, 2003 PMCID:170889

Schneider, C., Boeglin, W.E., Brash, A.R. Analysis of cyclooxygenase-substrate interactions using stereospecifically-labeled arachidonic acids. Adv Exp Med Biol, 507, 49-53, 2002

Schneider, Claus, Boeglin, William E, Prusakiewicz, Jeffery J, Rowlinson, Scott W, Marnett, Lawrence J, Samel, Nigulas, Brash, Alan R. Control of prostaglandin stereochemistry at the 15-carbon by cyclooxygenases-1 and -2. A critical role for serine 530 and valine 349. J Biol Chem, 277(1), 478-85, 2002

Schneider, Claus, Brash, Alan R. Lipoxygenase-catalyzed formation of R-configuration hydroperoxides. Prostaglandins Other Lipid Mediat, 68-69, 291-301, 2002

Schneider, Claus, Manier, M Lisa, Hachey, David L, Brash, Alan R. Detection of the 15-acetate of prostaglandin E2 methyl ester as a prominent component of the prostaglandins in the gorgonian coral Plexaura homomalla. Lipids, 37(2), 217-21, 2002

Kozak, K R, Prusakiewicz, J J, Rowlinson, S W, Schneider, C, Marnett, L J. Amino acid determinants in cyclooxygenase-2 oxygenation of the endocannabinoid 2-arachidonylglycerol. J Biol Chem, 276(32), 30072-7, 2001

Schneider, C, Keeney, D S, Boeglin, W E, Brash, A R. Detection and cellular localization of 12R-lipoxygenase in human tonsils. Arch Biochem Biophys, 386(2), 268-74, 2001

Schneider, C, Tallman, K A, Porter, N A, Brash, A R. Two distinct pathways of formation of 4-hydroxynonenal. Mechanisms of nonenzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals. J Biol Chem, 276(24), 20831-8, 2001

Shappell, S B, Gupta, R A, Manning, S, Whitehead, R, Boeglin, W E, Schneider, C, Case, T, Price, J, Jack, G S, Wheeler, T M, Matusik, R J, Brash, A R, Dubois, R N. 15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells. Cancer Res, 61(2), 497-503, 2001

Tijet, N, Schneider, C, Muller, B L, Brash, A R. Biogenesis of volatile aldehydes from fatty acid hydroperoxides: molecular cloning of a hydroperoxide lyase (CYP74C) with specificity for both the 9- and 13-hydroperoxides of linoleic and linolenic acids. Arch Biochem Biophys, 386(2), 281-9, 2001

Rowlinson, S W, Crews, B C, Goodwin, D C, Schneider, C, Gierse, J K, Marnett, L J. Spatial requirements for 15-(R)-hydroxy-5Z,8Z,11Z, 13E-eicosatetraenoic acid synthesis within the cyclooxygenase active site of murine COX-2. Why acetylated COX-1 does not synthesize 15-(R)-hete. J Biol Chem, 275(9), 6586-91, 2000

Schneider, C, Boeglin, W E, Brash, A R. Enantiomeric separation of hydroxy eicosanoids by chiral column chromatography: effect of the alcohol modifier. Anal Biochem, 287(1), 186-9, 2000

Schneider, C, Boeglin, W E, Lai, S, Cha, J K, Brash, A R. Synthesis and applications of stereospecifically (3)H-labeled arachidonic acids as mechanistic probes for lipoxygenase and cyclooxygenase catalysis. Anal Biochem, 284(1), 125-35, 2000

Schneider, C, Brash, A R. Stereospecificity of hydrogen abstraction in the conversion of arachidonic acid to 15R-HETE by aspirin-treated cyclooxygenase-2. Implications for the alignment of substrate in the active site. J Biol Chem, 275(7), 4743-6, 2000

Schneider, C. and Schreier, P. Catalytic properties of allene oxide synthase from flaxseed (Linum usitatissimum L.). Lipids, 33, 191-196, 1998

Schneider, C., Amberg, A., Feurle, J., Ross, A., Roth, M., Toth, G., and Schreier, P. 2-[4'-Hydroxy-3'-methoxy)-phenoxy]-4-(4"-hydroxy-3"-methoxy-phenyl)-8-hydroxy-6-oxo-3-oxabicyclo[3.3.0]-7-octene: Unusual product of the soybean lipoxygenase-catalyzed oxygenation of curcumin. J. Mol. Catal. B: Enzymatic, 4, 219-227, 1998

Herderich, M., Richling, E., Roscher, R., Schneider, C., Schwab, W., Humpf, H.-U., and Schreier, P. Application of atmospheric pressure ionization HPLC-MS-MS for the analysis of natural products. Chromatographia, 45, 127-132, 1997

Schneider, C., Schreier, P., and Herderich, M. Analysis of lipoxygenase-derived fatty acid hydroperoxides by electrospray ionization tandem mass spectrometry. Lipids, 32, 331-336, 1997

Schneider, C., Schreier, P., and Humpf, H.-U. Exciton-coupled circular dichroism (ECCD) in acyclic hydroxylated dienes: A sensitive method for the direct stereochemical assignment of lipoxygenase products. Chirality, 9, 563-567, 1997

Schneider, C., Wein, M., Harmsen, D., and Schreier, P. A fatty acid alpha-ketol, a product of the plant lipoxygenase pathway, is oxidized to 3(Z)-dodecendioic acid by a bacterial monooxygenase. Biochem. Biophys. Res. Commun., 232, 364-366, 1997

Postdoctoral Position Available

Postdoctoral Position Details
NIH-funded positions available for a start date of October 1, 2013. Candidates should have experience in structural analysis of small molecules using HPLC, NMR, LC-MS. A background in lipid or natural product biochemistry would be a big plus. We also welcome candidates that, in addition, are proficient in cell culture and molecular biology.
Our laboratory encourages international students to apply for post-graduate research. In particular, we are interested in recruiting Brazilian Science without Borders fellows. For information please contact the PI.

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