Claus Schneider, Ph.D.
Assistant Professor of Pharmacology
Vanderbilt University Medical Center, Department of Pharmacology
RRB 572, 23rd Ave S at Pierce
Nashville, TN 37232-6602
- M.S., 1992, University of Wrzburg,Germany
- Ph.D., 1997, University of Wrzburg, Germany
Discovery and characterization of novel lipid mediators. Mechanisms of oxygenation of fatty acids. Chemopreventive activity of curcumin.
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.
- 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.
- 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.
- 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, 47101-116, 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.
- 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.
- Gordon, ON, Schneider, C "Vanillin and ferulic acid: not the major degradation products of curcumin." Trends Molec. Med., 18361-363, 2012.
- 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.
- Schneider, C, Pozzi, A Cyclooxygenases and lipoxygenases in cancer. Cancer Metastasis Rev, 30(3-4), 277-94, 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.
- 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.
- 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.
- Schneider, C An update on products and mechanisms of lipid peroxidation. Mol Nutr Food Res, 53(3), 315-21, 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.
- 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.
- 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.
- 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.
- 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.
- 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, Pratt, DA, Porter, NA, Brash, AR Control of oxygenation in lipoxygenase and cyclooxygenase catalysis. Chem Biol, 14(5), 473-88, 2007.
- Schneider, C, Yu, Z, Boeglin, WE, Zheng, Y, Brash, AR Enantiomeric separation of hydroxy and hydroperoxy eicosanoids by chiral column chromatography. Methods Enzymol, 433145-57, 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.
- 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.
- Brash, AR, Yu, Z, Boeglin, WE, Schneider, C The hepoxilin connection in the epidermis. FEBS J, 274(14), 3494-502, 2007.
- 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.
- 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.
- 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.
- 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, Claus Chemistry and biology of vitamin E. Mol Nutr Food Res, 49(1), 7-30, 2005.
- 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.
- 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.
- 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 3238-47, 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.
- 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, 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, 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.
- 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.
- 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.
- 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.
- 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, 1233297-305, 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.
- Schneider, C., Boeglin, W.E., Brash, A.R Analysis of cyclooxygenase-substrate interactions using stereospecifically-labeled arachidonic acids. Adv Exp Med Biol, 50749-53, 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, 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.
- Schneider, Claus, Brash, Alan R Lipoxygenase-catalyzed formation of R-configuration hydroperoxides. Prostaglandins Other Lipid Mediat, 68-69291-301, 2002.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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, 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, 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., 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, 4219-227, 1998.
- Schneider, C. and Schreier, P "Catalytic properties of allene oxide synthase from flaxseed (Linum usitatissimum L.)." Lipids, 33191-196, 1998.
- 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., 232364-366, 1997.
- Schneider, C., Schreier, P., and Herderich, M "Analysis of lipoxygenase-derived fatty acid hydroperoxides by electrospray ionization tandem mass spectrometry." Lipids, 32331-336, 1997.
- 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, 45127-132, 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, 9563-567, 1997.