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Igor A. Kaltashov

Professor

Bioanalytical chemistry; biological and medicinal applications of mass spectrometry; structure, properties, delivery and mechanism of action of protein-based therapeutics.

Current Research
Biopharmaceuticals are a unique class of medicines due to their extreme structural complexity. The structure of these therapeutic proteins is critically important for their efficacy and safety, and the ability to characterize it at various levels (from sequence to conformation) is critical not only at the quality control stage, but also throughout the discovery and design stages. Biological mass spectrometry (MS) offers a variety of approaches to study structure and behavior of complex protein drugs and has already become a default tool for characterizing the covalent structure of protein therapeutics, including sequence and post-translational modifications. Recently, MS-based methods have also begun enjoying a dramatic growth in popularity as a means to provide information on higher order structure and dynamics of biotechnology products. In particular, several MS-based methods recently developed in our laboratory offer a convenient way to assess the integrity of protein conformation and monitor interactions of protein drugs with their therapeutic targets and other physiological partners using simple model systems. MS-based methods are also applied to study pharmacokinetics of biopharmaceutical products, where they begin to rival traditional immunoassays. MS already provides valuable support to all stages of development of biopharmaceuticals, from discovery to post-approval monitoring, and its impact on the field of biopharmaceutical analysis will undoubtedly continue to grow.

Learn more at https://www.umass.edu/chemistry/faculty/igor-kaltashov

Academic Background

  • Postdoctoral Training: Johns Hopkins University School of Medicine
  • PhD University of Maryland Baltimore County
  • MS Moscow Institute of Physics and Technology
C. Ren, C.E. Bobst, and I.A. Kaltashov. Exploiting His-tags for absolute quantitation of exogenous recombinant proteins in biological matrices: ruthenium as a protein tracer, Anal. Chem. 2019, 91, 7189-7198
B.B. Minsky, R.R. Abzalimov, C. Niu, Y. Zhao, Z. Kirsch, P.L. Dubin, S.N. Savinov, and I.A. Kaltashov. Mass spectrometry reveals a multifaceted role of glycosaminoglycan chains in factor Xa inactivation by antithrombin. Biochemistry, 2018, 57, 4880-4890
K. Muneeruddin, C.E. Bobst, R. Frenkel, D. Houde, I. Turyan, Z. Sosic and I.A. Kaltashov. Characterization of a PEGylated protein therapeutic by ion exchange chromatography with on-line detection by native ESI MS and MS/MS. Analyst 2017, 142, 336
Y. Zhao, R.R. Abzalimov, and I.A. Kaltashov. Interactions of intact unfractionated heparin with its client proteins can be probed directly using native electrospray ionization mass spectrometry. Anal. Chem. 2016, 88, 1711-1718
K. Muneeruddin, M. Nazzaro and I.A. Kaltashov. Characterization of intact protein conjugates and biopharmaceuticals using ion-exchange chromatography with online detection by native electrospray ionization mass spectrometry and top-down tandem mass spectrometry. Anal. Chem. 2015, 87, 10138-10145
G. Wang and I.A. Kaltashov. A new approach to characterization of the higher order structure of disulfide-containing proteins using hydrogen/deuterium exchange and top-down mass spectrometry. Anal. Chem. 2014, 86, 7293-7298
G. Wang, R.R. Abzalimov, C.E. Bobst, and I.A. Kaltashov. Conformer-specific characterization of non-native protein states with high spatial resolution using hydrogen exchange and top-down mass spectrometry. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 20087-20092
C.E. Bobst, S. Wang, W.-C. Shen, and I.A. Kaltashov. Mass spectrometry study of a transferrin-based protein drug reveals the key role of protein aggregation for successful oral delivery. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 13544-13548
 
Contact Info

Department of Chemistry
N369 Life Sciences Laboratory
240 Thatcher Way
Amherst, MA 01003-9292

(413) 545-1460
kaltashov@chem.umass.edu

https://www.umass.edu/chemistry/faculty/igor-kaltashov