School of Pharmacy

Miklos Guttman

Assistant Professor

Department of Medicinal Chemistry, Guttman Lab, Medicinal Chemistry Faculty

Telephone: (206) 543-1707

Email: mguttman@uw.edu

Website: PubMed

Education

  • 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

Research Interests

  • Understanding the structural and biophysical aspects of antigen recognition by the humoral immune system.
  • Development of structural mass spectrometry techniques for structural glycobiology.

Biography

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.

Research Overview

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.

Recent Publications

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. Review.

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.

Dissection of Fragmentation Pathways in Protonated N-Acetylhexosamines. Mookherjee A, Uppal SS, Guttman M. Anal Chem. 2018 Oct 16;90(20):11883-11891. doi: 10.1021/acs.analchem.8b01963. Epub 2018 Sep 25.

Conformational dynamics of P-glycoprotein in lipid nanodiscs and detergent micelles reveal complex motions on a wide time scale. Li MJ, Guttman M, Atkins WM. J Biol Chem. 2018 Apr 27;293(17):6297-6307. doi: 10.1074/jbc.RA118.002190. Epub 2018 Mar 6.

Bridging the structural gap of glycoproteomics with ion mobility spectrometry. Mookherjee A, Guttman M. Curr Opin Chem Biol. 2018 Feb;42:86-92. doi: 10.1016/j.cbpa.2017.11.012. Epub 2017 Dec 1. Review.

Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization. Torrents de la Peña A, Julien JP, de Taeye SW, Garces F, Guttman M, Ozorowski G, Pritchard LK, Behrens AJ, Go EP, Burger JA, Schermer EE, Sliepen K, Ketas TJ, Pugach P, Yasmeen A, Cottrell CA, Torres JL, Vavourakis CD, van Gils MJ, LaBranche C, Montefiori DC, Desaire H, Crispin M, Klasse PJ, Lee KK, Moore JP, Ward AB, Wilson IA, Sanders RW. Cell Rep. 2017 Aug 22;20(8):1805-1817. doi: 10.1016/j.celrep.2017.07.077.

Extracellular Matrix Proteins Mediate HIV-1 gp120 Interactions with α4β7. Plotnik D, Guo W, Cleveland B, von Haller P, Eng JK, Guttman M, Lee KK, Arthos J, Hu SL. J Virol. 2017 Oct 13;91(21). pii: e01005-17. doi: 10.1128/JVI.01005-17. Print 2017 Nov 1.

Gas-Phase Hydrogen/Deuterium Exchange for Distinguishing Isomeric Carbohydrate Ions. Uppal SS, Beasley SE, Scian M, Guttman M. Anal Chem. 2017 Apr 18;89(8):4737-4742. doi: 10.1021/acs.analchem.7b00683. Epub 2017 Mar 29.