个人简介

Ph.D. (1970) Stanford University Director, Ion Cyclotron Resonance Program, NHMFL

研究领域

Bioanalytical/Chemical Biology/Environment and Energy/Spectroscopy and Dynamics/Structural Biology

FOURIER TRANSFORM ION CYCLOTRON RESONANCE (FT-ICR) MASS SPECTROMETRY My research consists of the continuing development of new theory, techniques, and analytical/biological/environmental applications of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. We were the first to apply Fourier transform techniques to mass spectrometry, and more than 775 FT-ICR mass spectrometry systems based on our patents and papers have been bought or built worldwide. At our National NSF High-Field FT-ICR Mass Spectrometry Facility at the National High Magnetic Field Laboratory, we have built 7, 9.4, 9.4, and 14.5 tesla FT/ICR instruments, and are currently building a 21 T instrument for installation in 2013. Our instruments hold the world records for mass resolution and mass accuracy (e.g., see Figure), and attract hundreds of users and collaborators from all over the world. We continue to push the FT-ICR technique to its ultimate limits for mass resolution, mass range, and sensitivity. Our stored-waveform inverse Fourier transform ("SWIFT") excitation/detection scheme offers ultrahigh-resolution MS/MS with a single spectrometer as well as truly simultaneous multiple-ion monitoring. We use electrospray ionization, field desorption/ionization, and atmospheric pressure photoionization to produce mass spectra of substances with little or no volatility (e.g., biopolymers, drugs). We are developing robotic sample handling for generation and introduction of biologically interesting ions (e.g., oligosaccharides, phospholipids, peptides/proteins, RNA/DNA) into an ICR ion trap for ultrahigh-resolution MS or MS/MS analysis. We optimize MS/MS (electron capture dissociation, infrared multiphoton dissociation) methods to identify the primary amino acid sequence as well as the site(s) and nature (e.g., phosphorylation, glycosylation) of protein posttranslational modifications. Applications include discovery and characterization of disease biomarkers (e.g., Alzheimer's, kidney diseases). FT-ICR MS allows us to identify 100,000 components in a mixture without prior separation (GC, LC , gels), thereby changing the whole approach to mixture analysis. For each component, the elemental composition reveals the heteroatom content (numbers of N, S, O atoms), number of rings plus double bonds, and degree of alkylation, from which we correlate and ultimately predict the origin, properties, and behavior of petroleum crude oil and its distillates, as well as other complex mixtures (e.g., biofuels, wine). We are developing new numerical and graphical methods to recognize patterns in the enormous volume of data made available by FT-ICR MS (up to 8 Mwords per spectrum). We monitor H/D exchange by mass spectrometry to identify surface-exposed residues in proteins and protein complexes. When two proteins stick to each other, we can identify amino acid residues at the contact surface between the two proteins, as prospective drug targets. Applications range from drug screening to the mechanism of protein folding in the "chaperone" complex.

近期论文

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Mao, Y (Mao, Yuan); Tipton, JD (Tipton, Jeremiah D.); Blakney, GT (Blakney, Greg T.); Hendrickson, CL (Hendrickson, Christopher L.);Marshall, AG (Marshall, Alan G.) Valence Parity to Distinguish c ' and z(circle) Ions from Electron Capture Dissociation/Electron Transfer Dissociation of Peptides: Effects of Isomers, Isobars, and Proteolysis Specificity. ANALYTICAL CHEMISTRY 2011, Volume: 83 Issue: 20, 8024-8028 Blakney Greg T.; Hendrickson Christopher L.; Marshall Alan G. Predator data station: A fast data acquisition system for advanced FT-ICR MS experiments. INTERNATIONAL JOURNAL OF MASS SPECTROMETRY 2011, Volume: 306 Issue: 2-3 Special Issue: SI, 246-252 Zhang, Q (Zhang, Qian); Willison, LN (Willison, LeAnna N.); Tripathi, P (Tripathi, Pallavi); Sathe, SK (Sathe, Shridhar K.); Roux, KH(Roux, Kenneth H.); Emmett, MR (Emmett, Mark R.); Blakney, GT (Blakney, Greg T.); Zhang, HM (Zhang, Hui-Min); Marshall, AG (Marshall, AlanG.) Epitope Mapping of a 95 kDa Antigen in Complex with Antibody by Solution-Phase Amide Backbone Hydrogen/Deuterium Exchange Monitored by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. ANALYTICAL CHEMISTRY 2011, Volume: 83 Issue: 18, 7129-7136 Kaiser, NK (Kaiser, Nathan K.); Savory, JJ (Savory, Joshua J.); McKenna, AM (McKenna, Amy M.); Quinn, JP (Quinn, John P.) Hendrickson, CL (Hendrickson, Christopher L.); Marshall, AG (Marshall, Alan G.) Electrically Compensated Fourier Transform Ion Cyclotron Resonance Cell for Complex Mixture Mass Analysis. ANALYTICAL CHEMISTRY 2011, Volume: 83 Issue: 17, 6907-6910 Wang, X (Wang, Xu); Stewart, PA (Stewart, Paul A.); Cao, Q (Cao, Qiang); Sang, QXA (Sang, Qing-Xiang Amy); Chung, LWK (Chung, Leland W. K.); Emmett, MR (Emmett, Mark R.); Marshall, AG (Marshall, Alan G.) Characterization of the Phosphoproteome in Androgen-Repressed Human Prostate Cancer Cells by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry JOURNAL OF PROTEOME RESEARCH 2011, Volume: 10 Issue: 9, 3920-3928