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|Joshua Coon, PhD|
Research SummaryBioanalytical Chemistry, Chemical Biology, Systems Biology, Mass Spectrometry, Proteomics
My research group aims to catalyze evolution in the rapidly developing field of proteomics and to use these technologies to address fundamental problems in developmental biology. With an emphasis on ion chemistry and instrumentation, we develop and apply new, enabling mass spectrometry-based (MS) proteomic technologies. Past successes in instrumentation include: the coupling electron-transfer dissociation to an Orbitrap mass analyzer, the addition of a high resolution mass filter over an ion trap to increase throughput and isolation fidelity, the development of both collision- and photon-activated methods to boost ETD efficiency (ETcaD and AI-ETD, respectively), and the use of ETD reagents for spectral calibration to eliminate mass accuracy drift. Such cutting-edge tools allow us to examine, for example, the molecular events that commit human embryonic stem cells (hES cells) to exit the pluripotent state with unprecedented chemical detail and sensitivity. Here we are focused on intracellular signaling, the epigenetic regulation of pluripotency, and interpreting and monitoring epigenetic codes. Coupled with instrumentation, new methodology is a vital component in accomplishing our overarching goal. In this vein, we have led the way in using intelligent data acquisition logic (Decision Tree) ETD with collision-activated dissociation (CAD), using ETD with isobaric tagging for protein quantification, and using ETD with various proteases other than trypsin to increase proteome coverage. Finally, our informatics team works on unique spectra pre-processing routines, an ETD-specific search algorithm called zCore (now commercially available), and an open platform for ETD spectral processing (COMPASS).
McAlister GC, Phanstiel DH, Wenger CD, Lee MV, Coon JJ. Analysis of tandem mass spectra by FTMS for improved large-scale proteomics with superior protein quantification. Analytical Chemistry, 2010, 82 (1): 316-22.
Ledvina AR, Beauchene NA, McAlister GC, Syka JE, Schwartz JC, Griep-Raming J, Westphall MS, Coon JJ. Activated-ion electron transfer dissociation improves the ability of electron transfer dissociation to identify peptides in a complex mixture. Analytical Chemistry, 2010, 82 (24): 10068-10074.
Swaney DL, Wenger CD, Coon JJ. Value of using multiple proteases for large-scale mass spectrometry-based proteomics. Jouurnal of Proteome Research, 2010, 9 (3): 1323-1329.
Wenger CD, McAlister GC, Xia Q, Coon JJ. Sub-part-per-million precursor and product mass accuracy for high-throughput proteomics on an electron transfer dissociation-enabled orbitrap mass spectrometer. Molecular & Cell Proteomics, 2010, 9 (5): 754-763.
Swaney DL, Wenger CD, Thomson JA, Coon JJ. Human embryonic stem cell phosphoproteome revealed by electron transfer dissociation tandem mass spectrometry. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 (4): 995-1000.
Sadygov RG, Good DM, Swaney DL, Coon JJ. A New Probabilistic Database Search Algorithm for ETD Spectra. Journal of Proteome Research, 2009, 8 (6): 3198-205.
Ledvina AR, McAlister GC, Gardener MW, Smith SI, Madsen JA, Schwartz JC, Stafford GC Jr, Syka JEP, Brodbelt JS, and Coon JJ. Infrared Photo-Activation Reduces Peptide Folding and Hydrogen Atom Migration Following ETD Tandem Mass Spectrometry. Angewandte Chemie, 2009, 48 (45): 8526-8528.
Phanstiel D, Brumbaugh J, Berggren WT, Feng X, Levenstein ME, Thomson JA, Coon JJ. “Mass Spectrometry Identifies and Quantifies 74 Unique Histone H4 Isoforms in Differentiating Human Embryonic Stem Cells”. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105, 11, 4093-4098.
McAlister GC, Berggren WT, Griep-Raming J, Horning S, Makarov A, Phanstiel D, Stafford GC, Swaney DL, Syka JEP, Coon JJ. “A Proteomics Grade ETD-enabled Linear Ion Trap-Orbitrap Hybrid Mass Spectrometer.” Journal of Proteome Research, 2008, 7 (8), 6388-6394.
Swaney DL, McAlister GC, Coon JJ. “Decision Tree Driven Tandem Mass Spectrometry for Shotgun Proteomics.” Nature Methods, 2008, 5, 11, 959-964.
McAlister GC, Phanstiel D, Good DM, Berggren WT, Coon JJ. “Implementation of Electron Transfer Dissociation on a Hybrid Linear Ion Trap-Orbitrap Mass Spectrometer.” Analytical Chemistry, 2007, 79, 10, 3525-3534.
Good DM, McAlister GC, Phanstiel D, Coon JJ. “Performance Evaluation of Electron Transfer Dissociation.” Molecular and Cellular Proteomics, 2007, 6, 11, 1942-51.
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File last updated: September 19, 2011