研究领域

Analyticaglycobiolog ;Bioanalyticachemistr ;Glycomic ;Glycoproteomics/Proteomic ;Masspectrometry

Our group is interested in the macromolecular physiological changes associated with disease conditions, with an emphasis on different types of cancer. We pay particular attention to those alterations associated with various glycoconjugates [i.e. carbohydrates (commonly referred to as glycans), glycoproteins, and glycopeptides]. To study these biomolecules, we employ highly sensitive bioanalytical techniques, with liquid-chromatographic separations and mass spectrometry (MS) along with its tandem MS modes being the foundation of our methodologies. We are actively pursuing several different research areas, including developing new techniques to improve the overall fragmentation efficiency of glycopeptides by electron-transfer dissociation (ETD). We are also working on highly-sensitive methods to selectively enrich glycosylated molecules featuring specific monosaccharides. We are particularly interested in sialylated structures. We are then applying these methods to investigate in more detail complex biological mixtures. In one current study, we are building upon previous work which demonstrated that a number of fucosylated and/or sialylated glycans attached to serum proteins are significantly elevated in their abundance levels in pathological samples. Presently, the proteins bearing these carbohydrates remain tentatively documented, at best. We are therefore working to a) identify these proteins; b) locate their sites of glycosylation; and c) determine the influence of the disease condition on the site microheterogeneity. Our ultimate goal is perform detailed structural investigations of cancer cell lines and tissues to identify the key cell-surface glycoproteins, quantitate their abundance levels, and compare their glycosylation patterns to control samples, as these molecules may function as more reliable biomarker.

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Mitra, I.; Alley, Jr., W.R.; Goetz, J.A.; Vasseur, J.A.; Novotny, M.V.; Jacobson, S.C. """"Electrophoretic analysis of serum N-glycan samples from ovarian cancer patients using microfluidic devices"""" Journal of Proteome Research 2013, 12, 4490-4496. Alley, Jr., W.R.; Mann, B.F.; Hruska, V.; Novotny, M.V. """"Isolation and purification of glycoconjugates from biological sources by recycling liquid chromatography"""" Analytical Chemistry 2013, 85, 10408–10416. Alley, Jr., W.R.; Mann, B.F.; Novotny, M.V. """"High-sensitivity analytical approaches for the structural characterization of glycoproteins"""" Chemical Reviews 2013, 113, 2668-732. Alley, Jr., W.R.; Novotny, M.V. """"Structural glycomic analyses at high sensitivity: A decade of progress"""" Annual Review of Analytical Chemistry 2013, 6, 237-65. Novotny, M.V.; Alley, Jr., W.R. """"Recent trends in analytical and structural glycobiology"""" Current Opinion in Chemical Biology 2013, 17, 832-840. Novotny, M.V.; Alley, Jr., W.R.; Mann, B.F."""" Analytical glycobiology at high sensitivity: Current approaches and directions"""" Glycoconjugate Journal 2013, 30, 89-117. Vasseur, J.A.; Goetz, J.A.; Alley, Jr., W.R.; Novotny, M.V. """"Smoking and lung cancer-induced changes in N-glycosylation of blood serum proteins"""" Glycobiology 2012, 22, 1684-1708. Alley, Jr., W.R.; Vasseur, J.A.; Goetz, J.A.; et al. """"N-linked glycan structures and their expressions change in the blood sera of ovarian cancer patients"""" Journal of Proteome Research 2012, 11, 2283-2300. Alley, Jr., W.R.; Novotny, M.V. """"Glycomic analysis of sialic acid linkages in glycans derived from blood serum glycoproteins"""" Journal of Proteome Research 2010, 9, 3062-3072. Alley, Jr., W.R.; Madera, M.; Mechref, Y.; Novotny, M.V. """"Chip-based reversed-phase liquid chromatography-mass spectrometry of permethylated N-linked glycans: A potential methodology for cancer-biomarker discovery"""" Analytical Chemistry 2010, 82, 5095-5106. Alley, Jr., W.R.; Mechref, Y.; Novotny, M.V. """"Use of activated graphitized carbon chips for liquid chromatography/mass spectrometric and tandem mass spectrometric analyses of tryptic glycopeptides"""" Rapid Communications in Mass Spectrometry 2009, 23, 495-505. Alley, Jr., W.R.; Mechref, Y.; Novotny, M.V. """"Characterization of glycopeptides by combining collision-induced dissociation and electron-transfer dissociation mass spectrometry data"""" Rapid Communications in Mass Spectrometry 2009, 23, 161-170.