Education
- Ph.D. Cornell University, 1986
- M.S. Cornell University, 1983
- B.A. Cornell University, 1977
Research
My research group specializes in the development and application of Fourier transform mass spectrometry for solving difficult problems in bioanalytical chemistry. We are exploring new methods for analyzing the structural features of glycosaminoglycans (GAGs), a class of carbohydrates that play a central role in a number of important biological processes, including cellular communication, cell signaling, and regulation of biochemical pathways. Our approach uses electron-aided methods of ion activation (electron detachment dissociation, electron induced dissociation, and electron transfer dissociation) to dissociate GAG oligosaccharides, and to provide detailed data regarding sites of sulfation, acetylation, and uronic acid stereochemistry. We are exploring the use of chemometric analysis (principal component analysis and partial least squares discriminant analysis) for maximizing the amount of analytical information that can be extracted from the highly complex tandem mass spectra produced by electron detachment dissociation of GAGs. We are developing rapid and sensitive methods for measuring changes in the cellular levels of proteins. Our approach is to harvest complex protein mixtures from a cell, enzymatically digest the proteins into peptides, and to identify the peptides by accurate mass measurement using Fourier transform mass spectrometry. This process is aided by a combination of capillary scale separation methods, chemical derivitization methods using compounds synthesized in our laboratory, and isotope labeling. Other recent research projects include the use of advanced computational methods for carrying out multiparticle simulations of ion motion within the FTICR mass analyzer. These simulations give detailed information about ion-ion interactions, and provide insight into the limits of mass accuracy in FTICR mass spectrometry.
Selected Publications
Sanderson, P.; Stickney, M.; Leach, F. E., III; Xia, J.; Yu, Y.; Zhang, F.; Linhardt, R. J.; Amster, I. J. “Heparin/Heparan Sulfate Analysis by Capillary Zone Electrophoresis-Mass Spectrometry”, J. Chromatogr. A 2018, 1545, 75-83. DOI: 10.1016/j.chroma.2018.02.052.
Aebersold, R.; Agar, J. N.; Amster, I. J.; Baker, M.; Bertozzi, C. R.; Costello, C. E.; Cravatt, B. J.; Fenselau, C.; Garcia, B.; Ge, Y.; Gunawardena, J.; Hendrickson, R. C.; Hergenrother, P. J.; Huber, C.; Ivanov, A. R.; Jensen, O.; Jewett, M. C.; Kelleher, N. L.; Kiessling, L. L.; Krogan, N. J.; Larsen, M. R.; Loo, J. A.; Loo, R. R.; Lundberg, E.; MacCoss, M.; Mallick, P.; Mootha, V. K.; Muir, T. W.; Patrie, S. M.; Pesavento, J. J.; Pitteri, S. J.; Rodriguez; H.; Sandoval, W.; Schluter, H.; Sheeley, D. M.; Slavoff, S. A.; Smith, L. M.; Snyder, M. P.; Thomas, P. M.; Uhlen, M.; van der Donk, W. A.; van Eyk, J. E.; Vidal, M.; Walt, D. R.; White, F. M.; Williams, E. R.; Wohlschlager, T.; Wysocki, V. H.; Yates, N. A.; Young, N. L. “How Many Human Proteoforms are There?”, Nat. Chem. Biol. 2018, 14, 206-214. DOI: 10.1038/nchembio.2576.
Driver, J. A.; Nagornov, K. O.; Kozhinov, A. N.; Tsybin, Y. O.; Kharchenko, A.; Amster, I. J., “Multiparticle Simulations of Quadrupolar Ion Detection in an Ion Cyclotron Resonance Cell with Narrow Aperture Detection Electrodes”, J. Am. Soc. Mass Spectrom. 2018, 29, 51-62. DOI: 10.1007/s13361-017-1817-6.
Agyekum, I.; Pepi, L.; Yu, Y.; Li, J.; Yan, L.; Linhardt, R. J.; Chen, S.; Amster, I. J., “Structural Elucidation of Fucosylated Chondroitin Sulfates from Sea Cucumber Using FTICR-MS/MS”, Eur. J. Mass Spectrom. 2018, 24, 157-167. DOI: 10.1177/1469066717731900.
Yu, Y.; Duan, J.; Leach, F. E., III; Toida, T.; Zhang, H.; Zhang, F.; Amster, I. J.; Linhardt, R. J. “Sequencing the Dermatan Sulfate Chain of Porcine Decorin”, J. Am. Soc. Chem. 2017, 139, 16986-16995. DOI: 10.1021/jacs.7b10164.
Leach, F. E., III; Riley, N. M.; Westphall, M. S.; Coon, J. J.; Amster, I. J., “Negative Electron Transfer Dissociation Sequencing of Increasingly Sulfated Glycosaminoglycan Oligosaccharides on an Orbitrap Mass Spectrometer”, J. Am. Soc. Mass Spectrom. 2017, 28, 1844-1854. DOI: 10.1007/s13361-017-1709-9.
Agyekum, I; Zong, C.; Boons, G.-J.; Amster, I. J., “Single Stage MS/MS Analysis of the C-5 Uronic Acid Stereochemistry in Heparan Sulfate Tetrasaccharides Using Electron Detachment Dissociation”, J. Am. Soc. Mass Spectrom. 2017, 28, 1741-1750. DOI: 10.1007/s13361-017-1643-x.
Chen, Y.; Lin, L.; Agyekum, I.; Zhang, X.; St. Ange, K.; Yu, Y.; Liu, J.; Amster, I. J.; Linhardt, R. J., “Structural Analysis of Heparin-Derived 3-O-Sulfated Tetrasaccharides: Antithrombin Binding Site Variants”, J. Pharm. Sci. 2017, 106, 973-981. DOI: 10.1016/j.xphs.2016.11.023.
Lin, L.; Liu, X.; Zhang, F.; Chi, L.; Amster, I. J.; Leach III, F. E.; Xia, Q.; Linhardt, R. J. “Analysis of Heparin Oligosaccharides by Capillary Electrophoresis-Negative-Ion Electrospray Ionization Mass Spectrometry”, Analyt. Bioanalyt. Chem. 2017, 409, 411-420. DOI: 10.1007/s00216-016-9662-1.
Zhao, Y.; Singh, A.; Xu, Y.; Zong, C.; Zhang, F.; Boons, G.-J.; Liu, J.; Linhardt, R. L; Woods, R. J.; Amster, I. J., “Gas-Phase Analysis of the Complex of Fibroblast Growth Factor 1 with Heparan Sulfate: A Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study”, J. Am. Soc. Mass Spectrom. 2017, 28, 96-109. DOI: 10.1007/s13361-016-1496-8.
