个人简介

AB, Emmanuel College, Boston, MA MS, PhD, Georgetown University, Washington, DC

研究领域

Biopolymer structural studies based on development and application of mass spectral methods

Biopolymer structural studies based on development and application of mass spectral methods The objective of our research is to establish the detailed structures of biopolymers in order to understand their structure-activity relationships as they influence or reflect biological processes related to health, growth and development, and disease. Our particular focus for new method development is on the needs of glycobiology, since carbohydrates and their conjugates (glycoproteins, glycolipids, etc.) are involved in targeting and immune system recognition, nervous system growth and development, infection, parasite response, carcinogenesis, and other critical processes. The techniques for full structural characterization of these complex molecules are much less developed than are methods for linear biopolymers (proteins and oligonucleotides). Recent introduction of new mass spectral ionization methods and rapid progress in means for mass separation and detection now make it possible to perform structural studies on low picomole amounts of samples even when they are complex mixtures. In our research program we are refining and extending the tools of mass spectrometry and are applying them to studies of biopolymers undertaken with collaborators at BUSM and other institutions around and outside the US. Our laboratory is a Resource Center sponsored by the NIH National Center for Research Resources.

近期论文

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Complete Post Translational Modification Mapping of Pathogenic N. meningitidis Pilins Requires Top-Down Mass Spectrometry. Gault, J.; Malosse, C.; Machata, S.; Millien, C.; Podglajen, I.; Ploy, M.-C.; Costello, C. E.; Duménil, G.; Chamot-Rooke, J, Proteomics, 2013, in press. Evidence for a structural role for acid-fast lipids in oocyst walls of Cryptosporidium, Toxoplasma, and Eimeria. Bushkin GG, Motari E, Carpentieri A, Dubey JP, Costello CE, Robbins PW, Samuelson J. MBio. 2013 Sep 3;4(5):e00387-13. doi: 10.1128/mBio.00387-13. Mass Spectrometry of Glycans. Han, L.; Costello, C. E. Biochemistry (Moscow) 2013, 78, 710-720. STRAP PTM: Software Tool for Rapid Annotation and Differential Comparison of Protein Post-Translational Modifications. Spencer, J. L.; Bhatia, V. N.; Whelan, S. A.; Costello, C. E.; McComb, M. E. Curr. Protocols Bioinf., 2013, in press. The binding sites of monoclonal antibodies to the non-reducing end of Francisella tularensis O-antigen accommodate mainly the terminal saccharide.Lu Z, Rynkiewicz MJ, Yang CY, Madico G, Perkins HM, Wang Q, Costello CE, Zaia J, Seaton BA, Sharon J. Immunology. 2013 Nov;140(3):374-89. doi: 10.1111/imm.12150. Ultraviolet laser-induced cross-linking in peptides. Leo G, Altucci C, Bourgoin-Voillard S, Gravagnuolo AM, Esposito R, Marino G, Costello CE, Velotta R, Birolo L. Rapid Commun Mass Spectrom. 2013 Jul 30;27(14):1660-8. doi: 10.1002/rcm.6610. The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation. Smith BW, Rozelle SS, Leung A, Ubellacker J, Parks A, Nah SK, French D, Gadue P, Monti S, Chui DH, Steinberg MH, Frelinger AL, Michelson AD, Theberge R, McComb ME, Costello CE, Kotton DN, Mostoslavsky G, Sherr DH, Murphy GJ. Blood. 2013 Jul 18;122(3):376-85. doi: 10.1182/blood-2012-11-466722. Epub 2013 May 30. Epithelial Wounds Induce Differential Phosphorylation Changes in Response to Purinergic and EGF Receptor Activation. Kehasse A, Rich CB, Lee A, McComb ME, Costello CE, Trinkaus-Randall V. Am J Pathol. 2013 Oct 1. doi:pii: S0002-9440(13)00600-7. 10.1016/j.ajpath.2013.08.015. Detailed Glycan Structural Characterization by Electronic Excitation Dissociation.Yu X, Jiang Y, Chen Y, Huang Y, Costello CE, Lin C. Anal Chem. 2013 Oct 9. [Epub ahead of print] A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease. Drouin EE, Seward RJ, Strle K, McHugh G, Katchar K, Londoño D, Yao C, Costello CE, Steere AC. Arthritis Rheum. 2013 Jan;65(1):186-96. Mass Spectrometry of Glycans. Han, L.; Costello, C. E. Biochemistry (Moscow) 2013, 78, 710-720. β-1,3-glucan, which can be targeted by drugs, forms a trabecular scaffold in the oocyst walls of Toxoplasma and Eimeria. Bushkin GG, Motari E, Magnelli P, Gubbels MJ, Dubey JP, Miska KB, Bullitt E, Costello CE, Robbins PW, Samuelson J. MBio. 2012 Sep 25;3(5). Lipid sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1. Chinnapen DJ, Hsieh WT, te Welscher YM, Saslowsky DE, Kaoutzani L, Brandsma E, D’Auria L, Park H, Wagner JS, Drake KR, Kang M, Benjamin T, Ullman MD, Costello CE, Kenworthy AK, Baumgart T, Massol RH, Lencer WI. Dev Cell. 2012 Sep 11;23(3):573-86. Energy-dependent electron activated dissociation of metal-adducted permethylated oligosaccharides. Yu X, Huang Y, Lin C, Costello CE. Anal Chem. 2012 Sep 4;84(17):7487-94. Top-down study of β2-microglobulin deamidation. Li X, Yu X, Costello CE, Lin C, O’Connor PB. Anal Chem. 2012 Jul 17;84(14):6150-7. Protective B-cell epitopes of Francisella tularensis O-polysaccharide in a mouse model of respiratory tularaemia. Lu Z, Madico G, Roche MI, Wang Q, Hui JH, Perkins HM, Zaia J, Costello CE, Sharon J. Immunology. 2012 Jul;136(3):352-60. A typical preparation of Francisella tularensis O-antigen yields a mixture of three types of saccharides. Wang Q, Shi X, Leymarie N, Madico G, Sharon J, Costello CE, Zaia J. Biochemistry. 2011 Dec 20;50(50):10941-50. Determination of Lipid Composition of the Outer Layer of Bacterial Walls: Mass-spectrometric Approach. Elkin, Y. N.; Budnik, B. A.; Ivleva, V. B.; Nazarenko, E. L.; O’Connor, H. B.; Costello, C. E. Russ. J. Mass Spectrom., 2011, 8, 273-280. Oxidation of HRas cysteine thiols by metabolic stress prevents palmitoylation in vivo and contributes to endothelial cell apoptosis. Burgoyne JR, Haeussler DJ, Kumar V, Ji Y, Pimental DR, Zee RS, Costello CE, Lin C, McComb ME, Cohen RA, Bachschmid MM. FASEB J. 2012 Feb;26(2):832-41. Electron transfer dissociation of milk oligosaccharides. Han L, Costello CE. J Am Soc Mass Spectrom. 2011 Jun;22(6):997-1013. The human proteome project: current state and future direction. Legrain P, Aebersold R, Archakov A, Bairoch A, Bala K, Beretta L, Bergeron J, Borchers CH, Corthals GL, Costello CE, Deutsch EW, Domon B, Hancock W, He F, Hochstrasser D, Marko-Varga G, Salekdeh GH, Sechi S, Snyder M, Srivastava S, Uhlén M, Wu CH, Yamamoto T, Paik YK, Omenn GS. Mol Cell Proteomics. 2011 Jul;10(7):M111. Top-Down Analysis of Small Plasma Proteins Using an LTQ-Orbitrap. Potential for Mass Spectrometry-Based Clinical Assays for Transthyretin and Hemoglobin. Théberge R, Infusini G, Tong W, McComb ME, Costello CE. Int J Mass Spectrom. 2011 Mar 1;300(2-3):130-142. Chymotrypsin C is a co-activator of human pancreatic procarboxypeptidases A1 and A2. Szmola R, Bence M, Carpentieri A, Szabó A, Costello CE, Samuelson J, Sahin-Tóth M. J Biol Chem. 2011 Jan 21;286(3):1819-27. doi: 10.1074/jbc.M110.187369. Epub 2010 Nov 22 Seward, R. J.; Drouin, E. E.; Steere, A. C.; Costello, C. E. Peptides Presented by HLA-DR Molecules in Synovia of Patients with Rheumatoid Arthritis or Antibiotic-Refractory Lyme Arthritis. Mol Cell Proteomics2011, 10, M110 002477. Pubmed Link Zee, R. S.; Yoo, C. B.; Pimentel, D. R.; Perlman, D. H.; Burgoyne, J. R.; Hou, X.; McComb, M. E.; Costello, C. E.; Cohen, R. A.; Bachschmid, M. M. Redox regulation of sirtuin-1 by S-glutathiolation. Antioxidants & redox signaling2010, 13, 1023-32. Pubmed Link The antiretroviral lectin cyanovirin-N targets well-known and novel targets on the surface of Entamoeba histolytica trophozoites. Carpentieri A, Ratner DM, Ghosh SK, Banerjee S, Bushkin GG, Cui J, Lubrano M, Steffen M,Costello CE, O’Keefe B, Robbins PW, Samuelson J. Eukaryot Cell. 2010 Nov;9(11):1661-8. Peptides presented by HLA-DR molecules in synovia of patients with rheumatoid arthritis or antibiotic-refractory Lyme arthritis.Seward RJ, Drouin EE, Steere AC, Costello CE. Mol Cell Proteomics. 2011 Mar;10(3):M110.002477. Determination of Lipid Composition of the Outer Layer of Bacterial Walls: Mass-spectrometric Approach. Elkin, Y. N.; Budnik, B. A.; Ivleva, V. B.; Nazarenko, E. L.; O’Connor, H. B.; Costello, C. E. Russ. J. Mass Spectrom., 2011, 8, 273-280. Wada, Y.; Dell, A.; Haslam, S. M.; Tissot, B.; Canis, K.; Azadi, P.; Backstrom, M.; Costello, C. E.; Hansson, G. C.; Hiki, Y.; Ishihara, M.; Ito, H.; Kakehi, K.; Karlsson, N.; Kato, K.; Kawasaki, N.; Khoo, K. H.; Kobayashi, K.; Kolarich, D.; Kondo, A.; Lebrilla, C.; Nakano, M.; Narimatsu, H.; Novak, J.; Novotny, M. V.; Ohno, E.; Packer, N. H.; Renfrow, M. B.; Tajiri, M.; Thomsson, K. A.; Yagi, H.; Yu, S. Y.; Taniguchi, N. Comparison of Methods for Profiling O-glycosylation: HUPO Human Disease Glycomics/Proteome Initiative Multi-Institutional Study of IgA1. Mol Cell Proteomics2010, 9, 719-727. Pubmed Link Staples, G. O.; Naimy, H.; Yin, H.; Kileen, K.; Kraiczek, K.; Costello, C. E.; Zaia, J. Improved hydrophilic interaction chromatography LC/MS of heparinoids using a chip with postcolumn makeup flow. Anal. Chem.2010, 82, 516-22. Pubmed Link Role of glycosaminoglycan sulfation in the formation of immunoglobulin light chain amyloid oligomers and fibrils.Ren R, Hong Z, Gong H, Laporte K, Skinner M, Seldin DC, Costello CE, Connors LH, Trinkaus-Randall V. J Biol Chem. 2010 Nov 26;285(48):37672-82. doi: 10.1074/jbc.M110.149575. Epub 2010 Sep 24. Palaima, E.; Leymarie, N.; Stroud, D.; Mizanur, R. M.; Hodgkin, J.; Gravato-Nobre, M. J.; Costello, C. E.; Cipollo, J. F. The Caenorhabditis elegans bus-2 mutant reveals a new class of O-glycans affecting bacterial resistance. J Biol Chem2010, 285, 17662-72. Pubmed Link Li, X.; Lin, C.; Han, L.; Costello, C. E.; O’Connor, P. B. Charge remote fragmentation in electron capture and electron transfer dissociation. J Am Soc Mass Spectrom2010, 21, 646-56. Pubmed Link Ebbel, E. N.; Leymarie, N.; Schiavo, S.; Sharma, S.; Gevorkian, S.; Hersch, S.; Matson, W. R.; Costello, C. E. Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry. Anal Biochem2010, 399, 152-61. Pubmed Link Naimy, H.; Staples, G. O.; McComb, M.; Costello, C. E., J. Zaia, J.; Leymarie, N. Patterns of Tissue-Specific Glycosaminoglycan Expression Revealed by Tandem Mass Spectrometry and Statistical Methods. J. Biomol. Tech. 2010, 21(3 Suppl): S24–S25. Chatterjee, A.; Carpentieri, A.; Ratner, D. M.; Bullitt, E.; Costello, C. E.; Robbins, P. W.; Samuelson, J. Giardia cyst wall protein 1 is a lectin that binds to curled fibrils of the GalNAc homopolymer. PLoS Pathog2010, 6, e1001059. Pubmed Link Carpentieri, A.; Ratner, D. M.; Ghosh, S. K.; Banerjee, S.; Bushkin, G. G.; Cui, J.; Lubrano, M.; Steffen, M.; Costello, C. E.; O’Keefe, B.; Robbins, P. W.; Samuelson, J. The anti-retroviral lectin cyanovirin-N targets well-known and novel targets on the surface of Entamoeba histolytica trophozoites. Eukaryot Cell2010, 9, 1661-1668. Pubmed Link Young, D. C.; Kasmar, A.; Moraski, G.; Cheng, T. Y.; Waltz, A. J.; Hu, J.; Xu, X.; Endres, G. W.; Uzieblo, A.; Zajonc, D.; Costello, C. E.; Miller, M. J.; Moody, D. B. Synthesis of dideoxymycobactin antigens presented by CD1A reveals T cell fine specificity for natural lipopeptide structures. J Biol Chem2009, 284, 25087-25096. Pubmed Link Ying, W.; Perlman, D. H.; Li, L.; Theberge, R.; Costello, C. E.; McComb, M. E. Highly efficient and selective enrichment of peptide subsets combining fluorous chemistry with reversed-phase chromatography. Rapid Commun Mass Spectrom2009, 23, 4019-30. Pubmed Link Wang, Y.; Meriin, A. B.; Zaarur, N.; Romanova, N. V.; Chernoff, Y. O.; Costello, C. E.; Sherman, M. Y. Abnormal proteins can form aggresome in yeast: aggresome-targeting signals and components of the machinery. FASEB J2009, 23, 451-63. Pubmed Link Staples, G.; Bowman, M.; Costello, C. E.; Hitchcock, A.; Lau, J.; Leymarie, N.; Miller, C.; Naimy, H.; Shi, X.; Zaia, J. A Chip-based Amide-HILIC LC/MS Platform for Glycosaminoglycan Glycomics. Proteomics2009, 9, 686-695. Pubmed Link Singh, B. N.; Hayes, G. R.; Lucas, J. J.; Sommer, U.; Viseux, N.; Mirgorodskaya, E.; Trifonova, R. T.; Sassi, R. R.; Costello, C. E.; Fichorova, R. N. Structural details and composition of Trichomonas vaginalis lipophosphoglycan in relevance to the epithelial immune function. Glycoconj J2009, 26, 3-17. Pubmed Link Romesser, P. B.; Perlman, D. H.; Faller, D. V.; Costello, C. E.; McComb, M. E.; Denis, G. V. Development of a malignancy-associated proteomic signature for diffuse large B-cell lymphoma. The American journal of pathology2009, 175, 25-35. Pubmed Link Rex, S.; Beaulieu, L. M.; Perlman, D. H.; Vitseva, O.; Blair, P. S.; McComb, M. E.; Costello, C. E.; Freedman, J. E. Immune versus thrombotic stimulation of platelets differentially regulates signalling pathways, intracellular protein-protein interactions, and alpha-granule release. Thromb Haemost2009, 102, 97-110. Pubmed Link Perlman, D. H.; Bauer, S. M.; Ashrafian, H.; Bryan, N. S.; Garcia-Saura, M. F.; Lim, C. C.; Fernandez, B. O.; Infusini, G.; McComb, M. E.; Costello, C. E.; Feelisch, M. Mechanistic insights into nitrite-induced cardioprotection using an integrated metabolomic/proteomic approach. Circ Res2009, 104, 796-804. Pubmed Link Makkinje, A.; Near, R. I.; Infusini, G.; Vanden Borre, P.; Bloom, A.; Cai, D.; Costello, C. E.; Lerner, A. AND-34/BCAR3 regulates adhesion-dependent p130Cas serine phosphorylation and breast cancer cell growth pattern. Cell Signal2009, 21, 1423-35. Pubmed Link