Vanderbilt University School of Medicine

Schey, Kevin L , PhD
Professor of Biochemistry
Professor of Ophthalmology and Visual Sciences

Lab Url:

Phone Number: 936-6861


Schey, Kevin's picture

Office Address   Mailing Address

Suite 9160, MRB III

Mass Spectrometry Research Center Suite 9160, MRB III 37232

Research Specialty
Proteomics analysis in development and disease; mass spectrometry technology development.

Research Description
The Schey lab is interested in both method/instrument development in proteomics analysis as well as in applications of state-of-the-art proteomics technologies in the study of development and disease. Method development/technology projects include methods for integral membrane protein analysis, tandem mass spectrometry of intact proteins (top-down proteomics), spatially-resolved proteomics analysis, and quantitative proteomics. The major area of application is human lens protein modifications and protein-protein interactions. Other areas of interest are: proteomics analysis of heart valve development, and invertebrate (shrimp and oyster) innate immunity.

Integral membrane proteins play key roles in signaling, transport, and adhesion, yet they remain difficult to analyze using conventional proteomics methods. Our lab has developed methods to analyze integral membrane proteins and membrane associated proteins including their modifications. In addition, we have developed methods for membrane proteome analysis. Currently we are developing methods for spatially-resolved studies (see below), for tissue imaging of membrane proteins, and for examining the membrane protein phosphoproteome.
Standard proteomics analyses typically require tryptic digestion of the protein sample followed by LC/MS/MS analysis of the peptides in order to identify and quantitate the proteins present in the sample. This bottom-up approach relies on inferring protein level information from peptide level measurements. Top-down analysis involves analysis of the intact proteins for identification but requires sophisticated technologies and software. We have developed a method for top-down proteomics analysis in a MALDI TOF-TOF platform and generated a new software application for the interpretation of resulting data.
Spatially-resolved proteomics represents a critically important area of development that takes advantage of recent advances in instrumental sensitivity. The ability to examine region-specific changes in a proteome has wide applicability in both development and disease processes. Two approaches are being developed in our lab to address this issue: 1) laser capture microsdissection (LCM) coupled with shotgun proteomics analysis and 2) MALDI tissue imaging. We have combined our membrane protein analysis protocols with LCM capture to examine region-specific changes in the ocular lens membrane proteome. Also, we have developed new sample preparation methods to allow MALDI imaging of membrane proteins. The MALDI imaging method is being applied to lens aging, chick and mouse heart development, shrimp viral infection, brain changes in addiction, and lung infection.
Our long-standing project on ocular lens membrane proteins is focused on how these proteins change as lens cells differentiate and as they age. Since the proteins in the lens core are as old as the individual, the lens serves as a model tissue to study protein aging. Age- and cataract-specific modifications have been identified and regional changes in the membrane proteome are being examined. Functional consequences of lens protein modification are also being examined with confocal microscopic, molecular biology, and spectroscopic methods.

Grant, JE, Bradshaw AD, Schwacke JH, Baicu CF, Zile MR, Schey KL. Quantification of Protein Expression Changes in the Aging Left Ventricle of Rattus norvegicus. J. Proteom. Res, in press, , .

Grey AC and Schey KL. Age-related Changes in the Spatial Distribution of Human Lens Alpha-Crystallin Products by MALDI Imaging Mass Spectrometry. Invest. Ophthalmol. Vis. Sci., in press, , .

Lim J, Walker K, Sherwin T, Schey KL, Donaldson P. Confocal Microscopy Reveals a Zone of Membrane Remodelling in the Outer Cortex of the Human Lens. Invest. Ophthalmol. Vis. Sci, in press, , .

Wang Z and Schey KL. Phosphorylation and Truncation Sites of Bovine Lens Connexin 46 and Connexin 50. Exp. Eye Res, in press, , .

Grant, JE, Bradshaw, AD, Schwacke, JH, Baicu, CF, Zile, MR, Schey, KL. Quantification of Protein Expression Changes in the Aging Left Ventricle of Rattus norvegicus. J Proteome Res, , , 2009. PMCID:2752960

Grey, AC, Chaurand, P, Caprioli, RM, Schey, KL. MALDI Imaging Mass Spectrometry of Integral Membrane Proteins from Ocular Lens and Retinal Tissue (dagger). J Proteome Res, 8(7), 3278-83, 2009. PMCID:2715141

Grey, AC, Li, L, Jacobs, MD, Schey, KL, Donaldson, PJ. Differentiation-dependent modification and subcellular distribution of aquaporin-0 suggests multiple functional roles in the rat lens. Differentiation, 77(1), 70-83, 2009. PMCID:2696237

Grey, AC, Schey, KL. Age-related Changes in the Spatial Distribution of Human Lens {alpha}-Crystallin Products by MALDI Imaging Mass Spectrometry. Invest Ophthalmol Vis Sci, , , 2009.

Korlimbinis, A, Berry, Y, Thibault, D, Schey, KL, Truscott, RJ. Protein aging: truncation of aquaporin 0 in human lens regions is a continuous age-dependent process. Exp Eye Res, 88(5), 966-73, 2009. PMCID:2713177

Lim, JC, Walker, KL, Sherwin, T, Schey, KL, Donaldson, PJ. Confocal microscopy reveals zones of membrane remodelling in the outer cortex of the human lens. Invest Ophthalmol Vis Sci, , , 2009.

Robalino, J, Carnegie, RB, O''Leary, N, Ouvry-Patat, SA, de la Vega, E, Prior, S, Gross, PS, Browdy, CL, Chapman, RW, Schey, KL, Warr, G. Contributions of functional genomics and proteomics to the study of immune responses in the Pacific white leg shrimp Litopenaeus vannamei. Vet Immunol Immunopathol, 128(1-3), 110-8, 2009.

Xue, Q, Itoh, N, Schey, KL, Cooper, RK, La Peyre, JF. Evidence indicating the existence of a novel family of serine protease inhibitors that may be involved in marine invertebrate immunity. Fish Shellfish Immunol, 27(2), 250-9, 2009.

Grey, AC, Schey, KL. Distribution of bovine and rabbit lens alpha-crystallin products by MALDI imaging mass spectrometry. Mol Vis, 14, 171-9, 2008. PMCID:2254960

Hill, EG, Schwacke, JH, Comte-Walters, S, Slate, EH, Oberg, AL, Eckel-Passow, JE, Therneau, TM, Schey, KL. A statistical model for iTRAQ data analysis. J Proteome Res, 7(8), 3091-101, 2008. PMCID:2722948

Liu, Z, Schey, KL. Fragmentation of multiply-charged intact protein ions using MALDI TOF-TOF mass spectrometry. J Am Soc Mass Spectrom, 19(2), 231-8, 2008. PMCID:2288703

Rose, KM, Wang, Z, Magrath, GN, Hazard, ES, Hildebrandt, JD, Schey, KL. Aquaporin 0-calmodulin interaction and the effect of aquaporin 0 phosphorylation. Biochemistry, 47(1), 339-47, 2008.

Thibault, DB, Gillam, CJ, Grey, AC, Han, J, Schey, KL. MALDI tissue profiling of integral membrane proteins from ocular tissues. J Am Soc Mass Spectrom, 19(6), 814-22, 2008. PMCID:2430993

Wang, Z, Han, J, Schey, KL. Spatial differences in an integral membrane proteome detected in laser capture microdissected samples. J Proteome Res, 7(7), 2696-702, 2008. PMCID:2740381

Ouvry-Patat, SA, Schey, KL. Characterization of antimicrobial histone sequences and posttranslational modifications by mass spectrometry. J Mass Spectrom, 42(5), 664-74, 2007.

Xue, QG, Itoh, N, Schey, KL, Li, YL, Cooper, RK, La Peyre, JF. A new lysozyme from the eastern oyster (Crassostrea virginica) indicates adaptive evolution of i-type lysozymes. Cell Mol Life Sci, 64(1), 82-95, 2007.

Cook, LA, Schey, KL, Wilcox, MD, Dingus, J, Ettling, R, Nelson, T, Knapp, DR, Hildebrandt, JD. Proteomic analysis of bovine brain G protein gamma subunit processing heterogeneity. Mol Cell Proteomics, 5(4), 671-85, 2006.

DiNovo, AA, Schey, KL, Vachon, WS, McGuffie, EM, Olson, JC, Vincent, TS. ADP-ribosylation of cyclophilin A by Pseudomonas aeruginosa exoenzyme S. Biochemistry, 45(14), 4664-73, 2006.

Han, J, Schey, KL. MALDI tissue imaging of ocular lens alpha-crystallin. Invest Ophthalmol Vis Sci, 47(7), 2990-6, 2006.

Karnaukhova, E, Schey, KL, Crouch, RK. Circular dichroism and cross-linking studies of bacteriorhodopsin mutants. Amino Acids, 30(1), 17-23, 2006.

Lindsey Rose, KM, Gourdie, RG, Prescott, AR, Quinlan, RA, Crouch, RK, Schey, KL. The C terminus of lens aquaporin 0 interacts with the cytoskeletal proteins filensin and CP49. Invest Ophthalmol Vis Sci, 47(4), 1562-70, 2006.

Xue, QG, Waldrop, GL, Schey, KL, Itoh, N, Ogawa, M, Cooper, RK, Losso, JN, La Peyre, JF. A novel slow-tight binding serine protease inhibitor from eastern oyster (Crassostrea virginica) plasma inhibits perkinsin, the major extracellular protease of the oyster protozoan parasite Perkinsus marinus. Comp Biochem Physiol B Biochem Mol Biol, 145(1), 16-26, 2006.

Ervin, LA, Ball, LE, Crouch, RK, Schey, KL. Phosphorylation and glycosylation of bovine lens MP20. Invest Ophthalmol Vis Sci, 46(2), 627-35, 2005.

Liu, Z, Schey, KL. Optimization of a MALDI TOF-TOF mass spectrometer for intact protein analysis. J Am Soc Mass Spectrom, 16(4), 482-90, 2005.

Ball, LE, Garland, DL, Crouch, RK, Schey, KL. Post-translational modifications of aquaporin 0 (AQP0) in the normal human lens: spatial and temporal occurrence. Biochemistry, 43(30), 9856-65, 2004.

Han, J, Little, M, David, LL, Giblin, FJ, Schey, KL. Sequence and peptide map of guinea pig aquaporin 0. Mol Vis, 10, 215-22, 2004.

Han, J, Schey, KL. Proteolysis and mass spectrometric analysis of an integral membrane: aquaporin 0. J Proteome Res, 3(4), 807-12, 2004.

Patat, SA, Carnegie, RB, Kingsbury, C, Gross, PS, Chapman, R, Schey, KL. Antimicrobial activity of histones from hemocytes of the Pacific white shrimp. Eur J Biochem, 271(23-24), 4825-33, 2004.

Xue, QG, Schey, KL, Volety, AK, Chu, FL, La Peyre, JF. Purification and characterization of lysozyme from plasma of the eastern oyster (Crassostrea virginica). Comp Biochem Physiol B Biochem Mol Biol, 139(1), 11-25, 2004.

Ball, LE, Little, M, Nowak, MW, Garland, DL, Crouch, RK, Schey, KL. Water permeability of C-terminally truncated aquaporin 0 (AQP0 1-243) observed in the aging human lens. Invest Ophthalmol Vis Sci, 44(11), 4820-8, 2003.

Hamilton, MH, Cook, LA, McRackan, TR, Schey, KL, Hildebrandt, JD. Gamma 2 subunit of G protein heterotrimer is an N-end rule ubiquitylation substrate. Proc Natl Acad Sci U S A, 100(9), 5081-6, 2003. PMCID:154301

Walgren, JL, Vincent, TS, Schey, KL, Buse, MG. High glucose and insulin promote O-GlcNAc modification of proteins, including alpha-tubulin. Am J Physiol Endocrinol Metab, 284(2), E424-34, 2003.

Cook, LA, Wilcox, MD, Dingus, J, Schey, KL, Hildebrandt, JD. Separation and analysis of G protein gamma subunits. Methods Enzymol, 344, 209-33, 2002.

McIntire, WE, Schey, KL, Knapp, DR, Dingus, J, Hildebrandt, JD. Characterization of deamidated G protein subunits. Methods Enzymol, 344, 481-505, 2002.

Muradov, KG, Granovsky, AE, Schey, KL, Artemyev, NO. Direct interaction of the inhibitory gamma-subunit of Rod cGMP phosphodiesterase (PDE6) with the PDE6 GAFa domains. Biochemistry, 41(12), 3884-90, 2002.

Nishida, M, Schey, KL, Takagahara, S, Kontani, K, Katada, T, Urano, Y, Nagano, T, Nagao, T, Kurose, H. Activation mechanism of Gi and Go by reactive oxygen species. J Biol Chem, 277(11), 9036-42, 2002.

Schey, KL, Busman, M, Cook, LA, Hamm, HE, Hildebrandt, JD. Structural characterization of intact G protein gamma subunits by mass spectrometry. Methods Enzymol, 344, 586-97, 2002.

Cook, LA, Schey, KL, Cleator, JH, Wilcox, MD, Dingus, J, Hildebrandt, JD. Identification of a region in G protein gamma subunits conserved across species but hypervariable among subunit isoforms. Protein Sci, 10(12), 2548-55, 2001. PMCID:2374038

Morinelli, TA, Meier, GP, Schey, KL, Margolius, HS. Radioiodination of the stable metabolic fragment of bradykinin, RPPGF. Peptides, 22(12), 2169-74, 2001.

Roberts, JE, Finley, EL, Patat, SA, Schey, KL. Photooxidation of lens proteins with xanthurenic acid: a putative chromophore for cataractogenesis. Photochem Photobiol, 74(5), 740-4, 2001.

Schey, KL, Finley, EL. Identification of peptide oxidation by tandem mass spectrometry. Acc Chem Res, 33(5), 299-306, 2000.

Schey, KL, Little, M, Fowler, JG, Crouch, RK. Characterization of human lens major intrinsic protein structure. Invest Ophthalmol Vis Sci, 41(1), 175-82, 2000.

Schey, KL, Patat, S, Chignell, CF, Datillo, M, Wang, RH, Roberts, JE. Photooxidation of lens alpha-crystallin by hypericin (active ingredient in St. John''s Wort). Photochem Photobiol, 72(2), 200-3, 2000.

Schey, KL, Fowler, JG, Shearer, TR, David, L. Modifications to rat lens major intrinsic protein in selenite-induced cataract. Invest Ophthalmol Vis Sci, 40(3), 657-67, 1999.

Cook, LA, Schey, KL, Wilcox, MD, Dingus, J, Hildebrandt, JD. Heterogeneous processing of a G protein gamma subunit at a site critical for protein and membrane interactions. Biochemistry, 37(35), 12280-6, 1998.

Finley, EL, Dillon, J, Crouch, RK, Schey, KL. Identification of tryptophan oxidation products in bovine alpha-crystallin. Protein Sci, 7(11), 2391-7, 1998. PMCID:2143850

Finley, EL, Dillon, J, Crouch, RK, Schey, KL. Radiolysis-induced oxidation of bovine alpha-crystallin. Photochem Photobiol, 68(1), 9-15, 1998.

McIntire, WE, Dingus, J, Schey, KL, Hildebrandt, JD. Characterization of the major bovine brain Go alpha isoforms. Mapping the structural differences between the alpha subunit isoforms identifies a variable region of the protein involved in receptor interactions. J Biol Chem, 273(50), 33135-41, 1998.

McIntire, WE, Schey, KL, Knapp, DR, Hildebrandt, JD. A major G protein alpha O isoform in bovine brain is deamidated at Asn346 and Asn347, residues involved in receptor coupling. Biochemistry, 37(42), 14651-8, 1998.

Pawate, S, Schey, KL, Meier, GP, Ullian, ME, Mais, DE, Halushka, PV. Expression, characterization, and purification of C-terminally hexahistidine-tagged thromboxane A2 receptors. J Biol Chem, 273(35), 22753-60, 1998.

Finley, EL, Busman, M, Dillon, J, Crouch, RK, Schey, KL. Identification of photooxidation sites in bovine alpha-crystallin. Photochem Photobiol, 66(5), 635-41, 1997.

Schey, KL, Fowler, JG, Schwartz, JC, Busman, M, Dillon, J, Crouch, RK. Complete map and identification of the phosphorylation site of bovine lens major intrinsic protein. Invest Ophthalmol Vis Sci, 38(12), 2508-15, 1997.

Swamy-Mruthinti, S, Schey, KL. Mass spectroscopic identification of in vitro glycated sites of MIP. Curr Eye Res, 16(9), 936-41, 1997.

Artemyev, NO, Natochin, M, Busman, M, Schey, KL, Hamm, HE. Mechanism of photoreceptor cGMP phosphodiesterase inhibition by its gamma-subunits. Proc Natl Acad Sci U S A, 93(11), 5407-12, 1996. PMCID:39259

Schey, KL. Hydrophobic proteins and peptides analyzed by matrix-assisted laser desorption/ionization. Methods Mol Biol, 61, 227-30, 1996.

Wilcox, MD, Dingus, J, Balcueva, EA, McIntire, WE, Mehta, ND, Schey, KL, Robishaw, JD, Hildebrandt, JD. Bovine brain GO isoforms have distinct gamma subunit compositions. J Biol Chem, 270(9), 4189-92, 1995.

Wilcox, MD, Schey, KL, Busman, M, Hildebrandt, JD. Determination of the complete covalent structure of the gamma 2 subunit of bovine brain G proteins by mass spectrometry. Biochem Biophys Res Commun, 212(2), 367-74, 1995.

Busman, M, Knapp, DR, Schey, KL. Observation of large multimers in the electrospray ionization mass spectrometry of peptides. Rapid Commun Mass Spectrom, 8(2), 211-6, 1994.

Wilcox, MD, Schey, KL, Dingus, J, Mehta, ND, Tatum, BS, Halushka, M, Finch, JW, Hildebrandt, JD. Analysis of G protein gamma subunit heterogeneity using mass spectrometry. J Biol Chem, 269(17), 12508-13, 1994.

Artemyev, NO, Mills, JS, Thornburg, KR, Knapp, DR, Schey, KL, Hamm, HE. A site on transducin alpha-subunit of interaction with the polycationic region of cGMP phosphodiesterase inhibitory subunit. J Biol Chem, 268(31), 23611-5, 1993.

Finch, JW, Crouch, RK, Knapp, DR, Schey, KL. Mass spectrometric identification of modifications to human serum albumin treated with hydrogen peroxide. Arch Biochem Biophys, 305(2), 595-9, 1993.

McMillan, DC, Schey, KL, Meier, GP, Jollow, DJ. Chemical analysis and hemolytic activity of the fava bean aglycon divicine. Chem Res Toxicol, 6(4), 439-44, 1993.

Walle, T, Walle, UK, Thornburg, KR, Schey, KL. Stereoselective sulfation of albuterol in humans. Biosynthesis of the sulfate conjugate by HEP G2 cells. Drug Metab Dispos, 21(1), 76-80, 1993.

Schey, KL, Papac, DI, Knapp, DR, Crouch, RK. Matrix-assisted laser desorption mass spectrometry of rhodopsin and bacteriorhodopsin. Biophys J, 63(5), 1240-3, 1992. PMCID:1261426

Papac, DI, Schey, KL, Knapp, DR. Combination electrospray-liquid secondary ion mass spectrometry ion source. Anal Chem, 63(15), 1658-60, 1991.

Postdoctoral Position Available

Postdoctoral Position Details
A post-doctoral training position is available to develop MALDI imaging mass spectrometry methods for ocular lens tissue. A special focus is on lens proteins, lipids, and metabolites and their changing distributions with age. Other tissues of interest are retina, lung and heart.

Updated Date

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