Associate Professor, Medicinal Chemistry
Telephone: (206) 543-1707
- BS in Chemistry, 2003, University of California, Irvine
- PhD in Chemistry/Biochemistry, 2009, University of California, San Diego
- Postdoctoral Studies in viral surface glycoproteins and immune complexes, University of Washington
- Understanding the structural and biophysical aspects of antigen recognition by the humoral immune system.
- Development of structural mass spectrometry techniques for structural glycobiology.
Taking Students: Yes
Miklos “Mike” Guttman received his B.S. in Chemistry from the University of California, Irvine with a focus in organic chemistry. He transitioned into biochemistry and earned his Ph.D. from the University of California, San Diego with Elizabeth Komives examining the interactions that regulate cholesterol uptake. He received a NIH Ruth L. Krischstein F32 award to work with Kelly Lee’s group as a postdoc to apply structural mass spectrometry to understand how antibodies recognize the viral surface glycoprotein of HIV. More recently Mike has worked with the Global Health Vaccine Accelerator Platform (GH-VAP) through the Bill and Melinda Gates Foundation to characterize emerging biotherapeutics.
Antibody-antigen recognition is a critically important biological process, underlying the immune response and the mechanism of action of biotherapeutics and vaccines. Due to the size and complexity of intact antibody-antigen complexes, our understanding of what constitutes an effective antibody interaction is often limited to static structures of isolated subunits. Using emerging biophysical and structural tools such as structural mass spectrometry, our lab seeks to characterize the interactions of intact antibody-antigen complexes in their native solution state and use this information to advance the development of biotherapeutic approaches against infectious diseases and cancer. We are currently investigating such interactions for understanding antibody-mediated neutralization of staphylococcal enterotoxins and cancer recognition by immunoglobulin μ (IgM).
Glycosylation plays a role in nearly all aspects of biology, it is estimated that over 50% of the human proteome is decorated with glycosylation. Yet despite its importance, our knowledge of glycobiology has been hindered by the analytical challenges posed by the structural complexity of carbohydrates. Mass spectrometry provides a sensitive and rapid tool for analyzing protein glycosylation, but it provides little regarding stereochemistry or linkage information. Another focus of our lab is developing and implementing novel mass spectrometry-based methods for obtaining a higher level of structural information for biologically relevant glycans and oligosaccharides.
Combinatorial immune refocusing within the influenza hemagglutinin head elicits cross-neutralizing antibody responses. bioRxiv. 2023 May 24:2023.05.23.541996. doi: 10.1101/2023.05.23.541996. Preprint.
Structural dynamics reveal subtype-specific activation and inhibition of influenza virus hemagglutinin. J Biol Chem. 2023 Jun;299(6):104765. doi: 10.1016/j.jbc.2023.104765. Epub 2023 Apr 28.
Disordered region encodes α-crystallin chaperone activity toward lens client γD-crystallin. Proc Natl Acad Sci U S A. 2023 Feb 7;120(6):e2213765120. doi: 10.1073/pnas.2213765120. Epub 2023 Jan 31. PMID: 36719917
IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2. J Exp Med. 2022 Sep 5;219(9):e20220849. doi: 10.1084/jem.20220849. Epub 2022 Aug 8.
Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain. Structure. 2022 Sep 1;30(9):1269-1284.e6. doi: 10.1016/j.str.2022.05.017. Epub 2022 Jun 17. PMID: 35716664
Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems. Chem Rev. 2022 Apr 27;122(8):7562-7623. doi: 10.1021/acs.chemrev.1c00279. Epub 2021 Sep 7.
Rapid Assessment of Pepsin Column Activity for Reliable HDX-MS Studies. Vorauer C, Wrigley MS, Rincon Pabon JP, Watson MJ, Mundorff CC, Weis DD, Guttman M. J Am Soc Mass Spectrom. 2021 May 13. doi: 10.1021/jasms.1c00080. Online ahead of print.
Quadrivalent influenza nanoparticle vaccines induce broad protection. Boyoglu-Barnum S, Ellis D, Gillespie RA, Hutchinson GB, Park YJ, Moin SM, Acton OJ, Ravichandran R, Murphy M, Pettie D, Matheson N, Carter L, Creanga A, Watson MJ, Kephart S, Ataca S, Vaile JR, Ueda G, Crank MC, Stewart L, Lee KK, Guttman M, Baker D, Mascola JR, Veesler D, Graham BS, King NP, Kanekiyo M. Nature. 2021 Apr;592(7855):623-628. doi: 10.1038/s41586-021-03365-x. Epub 2021 Mar 24.
Linkage Memory in Underivatized Protonated Carbohydrates. Mookherjee A, Uppal SS, Murphree TA, Guttman M. J Am Soc Mass Spectrom. 2021 Feb 3;32(2):581-589. doi: 10.1021/jasms.0c00440. Epub 2020 Dec 22.
Simple Platform for Automating Decoupled LC-MS Analysis of Hydrogen/Deuterium Exchange Samples. Watson MJ, Harkewicz R, Hodge EA, Vorauer C, Palmer J, Lee KK, Guttman M. J Am Soc Mass Spectrom. 2021 Feb 3;32(2):597-600. doi: 10.1021/jasms.0c00341. Epub 2020 Dec 7.
Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2. Walls AC, Fiala B, Schäfer A, Wrenn S, Pham MN, Murphy M, Tse LV, Shehata L, O’Connor MA, Chen C, Navarro MJ, Miranda MC, Pettie D, Ravichandran R, Kraft JC, Ogohara C, Palser A, Chalk S, Lee EC, Guerriero K, Kepl E, Chow CM, Sydeman C, Hodge EA, Brown B, Fuller JT, Dinnon KH 3rd, Gralinski LE, Leist SR, Gully KL, Lewis TB, Guttman M, Chu HY, Lee KK, Fuller DH, Baric RS, Kellam P, Carter L, Pepper M, Sheahan TP, Veesler D, King NP. Cell. 2020 Nov 25;183(5):1367-1382.e17. doi: 10.1016/j.cell.2020.10.043. Epub 2020 Oct 31.
Rapid Differentiation of Chondroitin Sulfate Isomers by Gas-phase Hydrogen-deuterium Exchange. Alonge KM, Harkewicz R, Guttman M. Curr Mol Med. 2020;20(10):821-827. doi: 10.2174/1566524020666200915110707.
Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats. Alonge KM, Mirzadeh Z, Scarlett JM, Logsdon AF, Brown JM, Cabrales E, Chan CK, Kaiyala KJ, Bentsen MA, Banks WA, Guttman M, Wight TN, Morton GJ, Schwartz MW. Nat Metab. 2020 Oct;2(10):1025-1033. doi: 10.1038/s42255-020-00275-6. Epub 2020 Sep 7.
The influence of proline isomerization on potency and stability of anti-HIV antibody 10E8. Guttman M, Padte NN, Huang Y, Yu J, Rocklin GJ, Weitzner BD, Scian M, Ho DD, Lee KK. Sci Rep. 2020 Aug 31;10(1):14313. doi: 10.1038/s41598-020-71184-7.
Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Walls AC, Fiala B, Schäfer A, Wrenn S, Pham MN, Murphy M, Tse LV, Shehata L, O’Connor MA, Chen C, Navarro MJ, Miranda MC, Pettie D, Ravichandran R, Kraft JC, Ogohara C, Palser A, Chalk S, Lee EC, Kepl E, Chow CM, Sydeman C, Hodge EA, Brown B, Fuller JT, Dinnon KH 3rd, Gralinski LE, Leist SR, Gully KL, Lewis TB, Guttman M, Chu HY, Lee KK, Fuller DH, Baric RS, Kellam P, Carter L, Pepper M, Sheahan TP, Veesler D, King NP. bioRxiv. 2020 Aug 12:2020.08.11.247395. doi: 10.1101/2020.08.11.247395. Preprint.
Probing the Stability of Proline Cis/Trans Isomers in the Gas Phase with Ultraviolet Photodissociation. Silzel JW, Murphree TA, Paranji RK, Guttman MM, Julian RR. J Am Soc Mass Spectrom. 2020 Sep 2;31(9):1974-1980. doi: 10.1021/jasms.0c00242. Epub 2020 Aug 18.
Parallel Chemoselective Profiling for Mapping Protein Structure. Potter ZE, Lau HT, Chakraborty S, Fang L, Guttman M, Ong SE, Fowler DM, Maly DJ. Cell Chem Biol. 2020 Aug 20;27(8):1084-1096.e4. doi: 10.1016/j.chembiol.2020.06.014. Epub 2020 Jul 9.
Imidazolium Compounds as Internal Exchange Reporters for Hydrogen/Deuterium Exchange by Mass Spectrometry. Murphree TA, Vorauer C, Brzoska M, Guttman M. Anal Chem. 2020 Jul 21;92(14):9830-9837. doi: 10.1021/acs.analchem.0c01328. Epub 2020 Jul 7.
High-Precision, Gas-Phase Hydrogen/Deuterium-Exchange Kinetics by Mass Spectrometry Enabled by Exchange Standards. Uppal SS, Mookherjee A, Harkewicz R, Beasley SE, Bush MF, Guttman M. Anal Chem. 2020 Jun 2;92(11):7725-7732. doi: 10.1021/acs.analchem.0c00749. Epub 2020 May 18.
Structure-Activity Relationships for CYP4B1 Bioactivation of 4-Ipomeanol Congeners: Direct Correlation between Cytotoxicity and Trapped Reactive Intermediates. Kowalski JP, McDonald MG, Whittington D, Guttman M, Scian M, Girhard M, Hanenberg H, Wiek C, Rettie AE. Chem Res Toxicol. 2019 Dec 16;32(12):2488-2498. doi: 10.1021/acs.chemrestox.9b00330. Epub 2019 Dec 4.
Interplay of disordered and ordered regions of a human small heat shock protein yields an ensemble of ‘quasi-ordered’ states. Clouser AF, Baughman HE, Basanta B, Guttman M, Nath A, Klevit RE. Elife. 2019 Oct 1;8:e50259. doi: 10.7554/eLife.50259.
Quantitative analysis of chondroitin sulfate disaccharides from human and rodent fixed brain tissue by electrospray ionization-tandem mass spectrometry. Alonge KM, Logsdon AF, Murphree TA, Banks WA, Keene CD, Edgar JS, Whittington D, Schwartz MW, Guttman M. Glycobiology. 2019 Nov 20;29(12):847-860. doi: 10.1093/glycob/cwz060.
Recommendations for performing, interpreting and reporting hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments. Masson GR, Burke JE, Ahn NG, Anand GS, Borchers C, Brier S, Bou-Assaf GM, Engen JR, Englander SW, Faber J, Garlish R, Griffin PR, Gross ML, Guttman M, Hamuro Y, Heck AJR, Houde D, Iacob RE, Jørgensen TJD, Kaltashov IA, Klinman JP, Konermann L, Man P, Mayne L, Pascal BD, Reichmann D, Skehel M, Snijder J, Strutzenberg TS, Underbakke ES, Wagner C, Wales TE, Walters BT, Weis DD, Wilson DJ, Wintrode PL, Zhang Z, Zheng J, Schriemer DC, Rand KD. Nat Methods. 2019 Jul;16(7):595-602. doi: 10.1038/s41592-019-0459-y. Epub 2019 Jun 27.
Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry. Benhaim M, Lee KK, Guttman M. Protein Pept Lett. 2019;26(1):16-26. doi: 10.2174/0929866526666181212165037.
The ubiquitin ligase SspH1 from Salmonella uses a modular and dynamic E3 domain to catalyze substrate ubiquitylation. Cook M, Delbecq SP, Schweppe TP, Guttman M, Klevit RE, Brzovic PS. J Biol Chem. 2019 Jan 18;294(3):783-793. doi: 10.1074/jbc.RA118.004247. Epub 2018 Nov 20.