The University of Massachusetts Amherst

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 www.chem.umass.edu/people/kaltashovlab/

Academic Background

  • Postdoctoral Training: Johns Hopkins University School of Medicine
  • PhD University of Maryland Baltimore County
  • MS Moscow Institute of Physics and Technology
Influence of glycan modification on IgG1 biochemical and biophysical properties. Pawlowski JW, Bajardi-Taccioli A, Houde D, Feschenko M, Carlage T, Kaltashov IA.J Pharm Biomed Anal. 2018 Mar 20;151:133-144. doi: 10.1016/j.jpba.2017.12.061. Epub 2018 Jan 3.
Multi-step conformational transitions in heat-treated protein therapeutics can be monitored in real time with temperature-controlled electrospray ionization mass spectrometry. Wang G, Bondarenko PV, Kaltashov IA. Analyst. 2018 Feb 7;143(3):670-677. doi: 10.1039/c7an01655g. Epub 2018 Jan 5.
Overcoming the Hydrolytic Lability of a Reaction Intermediate in Production of Protein/Drug Conjugates: Conjugation of an Acyclic Nucleoside Phosphonate to a Model Carrier Protein. Xu S, Kaltashov IA.Mol Pharm. 2017 Aug 7;14(8):2843-2851. doi: 10.1021/acs.molpharmaceut.7b00410. Epub 2017 Jul 28.
Characterization of a PEGylated protein therapeutic by ion exchange chromatography with on-line detection by native ESI MS and MS/MS. Muneeruddin K, Bobst CE, Frenkel R, Houde D, Turyan I, Sosic Z, Kaltashov IA.Analyst. 2017 Jan 16;142(2):336-344. doi: 10.1039/c6an02041k
S. Xu and I.A. Kaltashov. Evaluation of gallium as a tracer of exogenous hemoglobin-haptoglobin complexes for targeted drug delivery applications. J. Am. Soc. Mass Spectrom., 2016, 27, 2025-2032.
H. Zhao, S. Wang, S.N. Nguyen, S.G. Elci and I.A. Kaltashov. Evaluation of non-ferrous metals as potential in vivo tracers of transferrin-based therapeutics. J. Am. Soc. Mass Spectrom. 2016, 27, 211-219.
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.
K. Muneeruddin, J.J. Thomas, P.A. Salinas and I.A. Kaltashov.* Characterization of small protein aggregates and oligomers using size exclusion chromatography with on-line detection by native electrospray ionization mass spectrometry. Anal. Chem. 2014, 86, 10692-10699
I.A. Kaltashov, C.E. Bobst, S.N. Nguyen, S. Wang. Emerging mass spectrometry-based approaches to probe protein-receptor interactions: focus on overcoming physiological barriers. Adv. Drug Deliv. Rev., 2013, 65, 1020-1030
S.N. Nguyen, C.E. Bobst, I.A. Kaltashov. Mass spectrometry-guided optimization and characterization of a biologically active transferrin-lysozyme model drug conjugate. Mol. Pharmaceutics, 2013, 10, 1998-2007
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

www.chem.umass.edu/people/kaltashovlab/