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James Graham Brown Endowed Chair of Structural Biology; Professor of Medicine; Leader, Structural Biology Program
Research ProgramStructural Biology
Research InterestsMy research interests are in the analysis of macromolecular interactions involved in cellular regulation, using methods of solution state NMR and other biophysical approaches. We are especially concerned with protein-DNA and protein-protein interactions, and the determination of the mechanism of specific recognition via a detailed understanding of the effect of interactions on conformation, dynamics and energetics. This requires both experimental and theoretical approaches. In collaboration with Dr. Fan, we are developing methods for studying metabolism in cancer and normal cells using NMR isotopomer analyses of pathway fluxes.
EducationB.Sc., University College London, England, Biochemistry, 1972-1975
Ph.D., University College London, England, Biochemistry, 1975-1979
Research and Professional Experience
1979-1983
Post doctoral Fellow, Biophysical Chemistry, Biozentrum, Basel, Switzerland
1983-1986
Post doctoral Fellow, Stanford Magnetic Resonance Laboratory, Stanford University
1986-1994
Staff Scientist, National Institute for Medical Research, London, UK
1994-2001
Senior Staff Scientist, National Institute for Medical Research, London
2001-present
Professor of Medicine, University of Louisville
Director, James Graham Brown Cancer Center NMR Facility
2002-present
Professor of Chemistry (joint), University of Louisville
Editorial Board Nucleic Acids Research
Editorial Board Journal of Structural and Functional Genomics
1997-2000
Committee British Biophysical Society
Selected Awards and Professional Honors
Honorary Research Fellow, Department of Biochemistry and Molecular Biology, University College London
1983-1985
EMBO Fellow, Stanford University
James Graham Brown Endowed Chair of Structural Biology, University of Louisville
PublicationsTaylor IA, McIntosh PB, Pala P, Treiber MK, Howell S, Lane AN, Smerdon, SJ. Characterization of the DNA-Binding Domains from the Yeast Cell-Cycle Transcription Factors Mbp1 and Swi4. Biochemistry 39:3943-54, 2000
McIntosh PB, Taylor IA, Frenkiel TA, Smerdon SJ, Lane AN. The influence of DNA-binding on the backbone dynamics of the yeast cell-cycle protein Mbp1. J Biomolec NMR 16:183-96, 2000
Lane AN, Jenkins TC. Thermodynamics of nucleic acids and their interactions with ligands. Q Rev Biophys 33, 255-306, 2000
Lane AN, Hays LM, Tsvetkova N, Feeney RE, Crowe LM, Crowe JH. Comparison of the solution confor-mation and dynamics of antifreeze glycoproteins from Antarctic fish. Biophys J 78:3195-3207, 2000.
Gopal B, Papavinasasundaram KG, Dodson GG, Colston MJ, Major SA, Lane AN. Spectroscopic and thermodynamic characterisation of the transcription antitermination factor NusE and its interaction with NusB from Mycobacterium tuberculosis. Biochemistry 40:920-8, 2001
Alexandrovich A, Czisch M, Frenkiel TA, Moolenaar GF, Goosen N, Sanderson MR, Lane AN. Quaternary structure, thermodynamics and dynamics ofthe C-terminal domain of UvrB. J Biol Ster Dyn 19:219-36, 2001
Lane AN, Kelly G, Ramos A, Frenkiel TA. Determining binding sites in protein-nucleic acid complexes by cross-saturation. J Biomolec NMR 21:127-39, 2001
Nair M, McIntosh PB, Frenkiel TA, Kelly G, Taylor IA, Smerdon SJ, Lane AN. NMR structure of the DNA-binding domain of the cell cycle protein, Mbp1 from Saccharomyces cerevisiae. Biochemistry 42:1266-73, 2003
Gyi JI, Gao D, Conn GL, Trent JO, Brown T, Lane AN. The solution structure of a DNA*RNA duplex containing 5-propynyl U and C; comparison with 5-Me modifications. Nucleic Acids Res 31:2683-93, 2004
Fan TW, Lane AN, Chekmenev E, Wittebort RJ, Higashi RM. Synthesis and physico-chemical properties of peptides in soil humic substances. J Peptide Res 63(3):253-64, 2004.
Ramos A, Lane AN, Hollingworth D, Fan TW. Secondary structure and stability of the selenocysteine insertion sequences (SECIS) for human thioredoxin reductase and glutathione peroxidase. Nucleic Acids Res 32(5):1746-55, 2004
Fan TW, Lane AN, Higashi RM. An electrophoretic profiling method for thiol-rich phytochelations and metallothioneins. Phytochem Anal 15(3):175-83, 2004
Fan T W-M, Higashi RM, Lane AN. The promise of metabolomics in cancer molecular therapeutics. Current Opin. Molec. Ther 6(6):584-92, 2004 Review
Arumugam S, Gray RD, Lane AN. 1H, 15N and 13C assignments of the alkaline proteinase inhibitor APRin from Pseudomonas aeruginosa. J Biomol NMR 31(3):265-6, 2005
Lane AN, Arumugam S. Improving NMR sensitivity in room temperature and cooled probes with dipolar ions. J Magn Reson 173(2):339-43, 2005
Booth J, Brown T, Vadhia SJ, Lack O, Cummins WJ, Trent JO, Lane AN. Determining the origin of the stabilization of DNA by 5-aminopropynylation of pyrimidines. Biochemistry 44(12):4710-9, 2005
Fan TW, Higashi RM, Lane AN. Integrating metabolomics and transcriptomics for probing SE anticancer mechanisms. Drug Metab Rev 38(4):707-32, 2006 Review
Telang S, Yalcin A, Clem AL, Bucala R, Lane AN, Eaton JW, Chesney J. Ras transformation requires metabolic control by 6-phosphofructo-2-kinase. Oncogene 25(55):7225-34, 2006
Telang S, Lane AN, Nelson KK, Arumugam S, Chesney J. The oncoprotein H-RasV12 increases mitochondrial metabolism. Mol Cancer 6:77, 2007
Kurtoglu M, Gao N, Shang J, Maher JC, Lehrman MA, Wangpaichitr M, Savaraj N, Lane AN, Lampidis TJ. Under normoxia, 2-deoxy-D-glucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation. Mol Cancer Ther 6(11):3049-58, 2007
Lane AN, Chaires JB, Gray RD, Trent JO. Stability and kinetics of G-quadruplex structures. Nucleic Acids Res 36(17):5482-515, 2008
Deleeuw L, Tchernatynskaia AV, Lane AN. Thermodynamics and specificity of the Mbp1-DNA interaction. Biochemistry 47(24):6378-85, 2008
Lane AN, Fan TW, Higashi RM. Stable isotope-assisted metabolomics in cancer research. IUBMB Life 60(2):124-9, 2008 Review
Arumugam S, Gray RD, Lane AN. NMR structure note: alkaline proteinase inhibitor APRin from Pseudomonas aeruginosa. J Biomol NMR 40(3):213-7, 2008
Lane AN, Fan TW, Higashi RM. Isotopomer-based metabolomic analysis by NMR and mass spectrometry. Methods Cell Biol 84:541-88, 2008
Lane AN, Fan TW, Higashi RM. Stable isotope-assisted metabolomics in cancer research. IUBMB Life 60(2):124-9, 2008. Review
DeLeeuw L, Tchernatynskaia AV, Lane AN. Thermodynamics and specificity of the Mbp1-DNA interaction. Biochemistry 47(24):6378-85, 2008
Lane AN, Chaires JB, Gray RD, Trent JO. Stability and kinetics of G-quadruplex structures. Nucleic Acids Res 36(17):5482-515, 2008; PMC2553573. Review
Thornburg JM, Nelson KK, Clem BF, Lane AN, Arumugam S, Simmons A, Eaton JW, Telang S, Chesney J. Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res 10(5):R84, 2008; PMC2614520
Fan TW, Kucia M, Jankowski K, Higashi RM, Ratajczak J, Ratajczak MZ, Lane AN. Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes. Mol Cancer 7:79, 2008; PMC2577687
Fan TW, Lane AN, Higashi RM, Bousamra M 2nd, Kloecker G, Miller DM. Metabolic profiling identifies lung tumor responsiveness to erlotinib. Exp Mol Pathol 87(1):83-6, 2009; PMC2729693
Lane AN, Fan TW, Higashi RM, Tan J, Bousamra M, Miller DM. Prospects for clinical cancer metabolomics using stable isotope tracers. Exp Mol Pathol 86(3):165-73, 2009; PMC2685876
Fan TW, Lane AN, Higashi RM, Farag MA, Gao H, Bousamra M, Miller DM. Altered regulation of metabolic pathways in human lung cancer discerned by (13)C stable isotope-resolved metabolomics (SIRM). Mol Cancer 8:41, 2009; PMC2717907
Lane AN, Fan TW, Xie Z, Moseley HN, Higashi RM. Isotopomer analysis of lipid biosynthesis by high resolution mass spectrometry and NMR. Anal Chim Acta 651(2):201-8, 2009; PMC2757635
Chernatynskaya AV, Deleeuw L, Trent JO, Brown T, Lane AN. Structural analysis of the DNA target site and its interaction with Mbp1. Org Biomol Chem 7(23):4981-91, 2009
Yalcin A, Clem B, Makoni S, Clem A, Nelson K, Thornburg J, Siow D, Lane AN, Brock SE, Goswami U, Eaton JW, Telang S, Chesney J. Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling. Oncogene 29(1):139-49, 2010
Contact InfoCTR Building
505 South Hancock Street
Louisville, KY 40202
Phone: (502) 852-3067
Fax: (502) 852-5679
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