Miklos Guttman

Assistant Professor

Department of Medicinal Chemistry, Medicinal Chemistry Faculty

Expertise: Glycobiology, Mass Spectrometry, Structural Biology

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.

Selected Publications

  • Guttman, M. , Lee, K.K. “Site-specific mapping of sialic acid linkage isomers by ion mobility spectrometry.” Anal. Chem., 2016 May 17(88), 5212-7. PubMed link.
  • Guttman, M., Wales, T., Whittington, D., Engen, J.R., Brown J., Lee, K.K.  “Tuning a High Transmission Ion Guide to Prevent Gas-Phase Proton Exchange During H/D Exchange MS Analysis. Am. Soc. Mass Spectrom., 2016 Apr;27(4):662-8. PubMed link.
  • de Taeye, S.W., Ozorowski, G., Torrents de la Peña, A., Guttman, M., Julien, J.P., et al. “Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposures of non-neutralizing epitopes.” Cell, 2015 Dec 17;163(7):1702-15. PubMed link.
  • Guttman, M., Lee, K.K., “Isotope Labeling of Biomolecules: Structural Analysis of Viruses by HDX-MS.” Methods Enzymol., 2016;566:405-26. PubMed link.
  • Gupta, S., Guttman, M., Leverenz, R.L., Zhumadilova, K., Pawlowski, E.G., Petzold, C.J., Lee, K.K., Ralston, C., Kerfield, C.A. “Local and Global Structural Drivers for the Photoactivation of the Orange Carotenoid Protein.” PNAS, 2015 Oct 13;112(41):E5567-74. PubMed link.
  • Guttman, M., Cupo, A., Julien, J.P., Sanders, R.W., Wilson, I.A., Moore, J.P., Lee, K.K. “Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env.” Commun., 2015 Feb 5;6:6144. PubMed link.
  • Guttman, M., Scian, M., Lee, K.K. “Tracking hydrogen/deuterium exchange at glycan sites in glycoproteins by mass spectrometry.” Chem., 2011 Oct 1;83(19):7492-9. PubMed link.