Associate Professor
Post-Doc, Johns Hopkins University School of Medicine; Ph.D., University of Maryland Baltimore County; M.S., Moscow Institute of Physics and Technology

Bioanalytical Chemistry
Novel mass spectrometry-based strategies to study biopolymer architecture, dynamics and interaction; controlled disorder as a universal facilitator of binding processes; small ligand transport and delivery; higher order structure and dynamics of biopharmaceutical products.

Department of Chemistry, 701A LGRT
University of Massachusetts
710 North Pleasant Street
Amherst, MA 01003-9336

office: 267E Goessmann Laboratory
tel: 413-545-1460 fax: 413-545-3757

kaltashov@chem.umass.edu

Kaltashov Research Group

Principal Research Interests
 
Biological processes are executed through a sophisticated web of biomolecular interactions. Learning how to pull the strings of this web with a high degree of selectivity by manipulating certain interactions will provide enormous benefit to the entire field of life sciences and especially to molecular therapeutics. However, it will also require better tools to study biomolecular structure, dynamics and interactions in complex systems.

Experimental investigation of architecture and conformational heterogeneity of proteins, as well as their associations with each other, remains a very challenging task. Characterization of higher order structure and dynamics of other biopolymers, particularly those whose synthesis is not genetically controlled, is even more challenging. One particularly unforgiving limitation inherent to almost all experimental techniques used to probe macromolecular structure and dynamics is the extreme difficulty in characterizing behavior of individual biopolymers in multi-component systems, which arises due to inevitable signal interference from different species. Mass spectrometry (MS) has emerged relatively recently as an attractive alternative in the studies of protein architecture and dynamics, capable of providing information on protein conformation at various levels. It also has a tremendous potential for probing higher order structure of other biopolymers, which is yet to be fully explored.

One of the focal points of our research efforts is developing novel mass spectrometry-based strategies to study biopolymer architecture, dynamics and interactions with each other. One of such strategies utilizes chemometric tools to detect and characterize multiple protein conformers in solution. Dynamics and structure of these states is probed by a combination of protein chemistry in solution (hydrogen/deuterium exchange to label dynamic segments within the protein) and in the gas phase (protein ion fragmentation to measure the deuterium content across the protein sequence). The latter becomes possible due to a rapid progress in ion fragmentation techniques, which allow primary structure of large biopolymers to be determined in a single experiment. The experimental tools developed in our laboratory are applied to study biopolymer behavior in a variety of systems, ranging from metal delivery to tissues via a transferrin cycle to modulation of protein function by glycosaminoglycans and synthetic polymers.

R.R. Abzalimov, P.L. Dubin and I.A. Kaltashov, “Glycosaminoglycans as Naturally Occurring Combinatorial Libraries: Developing a Mass Spectrometry-Based Strategy for Characterization of Anti-Thrombin Interaction with Low Molecular Weight Heparin and Heparin Oligomers,” Anal. Chem. 79, 6055-6063 (2007).

W.P. Griffith and I.A. Kaltashov, “Protein Conformational Heterogeneity as a Binding Catalyst: ESI MS Study of Hemoglobin H Formation,” Biochemistry 46, 2020-2026 (2007).

I.A. Kaltashov, “Macromolecular Conformations in Solution from Charge-State Distributions Produced by Electrospray Ionization,” In: Encyclopedia of Mass Spectrometry, Vol. 8: Molecular Ionization. M. L. Gross, ed. San Diego, CA: Elsevier, pp. 746-756 (ISBN 0080438016) (2006).

M. Zhang and I.A. Kaltashov, “Mapping of Protein Disulfide Bonds Using Negative Ion Fragmentation with a Broadband Precursor Selection,” Anal. Chem. 78, 4820-4829 (2006).

J.K. Hoerner, H. Xiao and I.A. Kaltashov. Structural and dynamic characteristics of a partially folded state of ubiquitin revealed by hydrogen exchange mass spectrometry. Biochemistry, 2005, 44, 11286 -11294

I.A. Kaltashov and A. Mohimen. Estimates of protein surface areas in solution by electrospray ionization mass spectrometry. Anal. Chem., 2005, 77, 5370-5379

I.A. Kaltashov, S.J. Eyles. Mass Spectrometry in Biophysics: Conformation and Dynamics of Biomolecules. New York: John Wiley & Sons, Inc., 2005

H. Xiao, I.A. Kaltashov. Transient structural disorder as a facilitator of protein-ligand binding: native H/D exchange - mass spectrometry study of cellular retinoic acid binding protein I. J. Am. Soc. Mass Spectrom., 2005, 16, 869–879

H. Xiao, J.K. Hoerner, S.J. Eyles, A. Dobo, E. Voigtman, A.I. Mel’?uk, I.A. Kaltashov. Mapping protein energy landscapes with amide hydrogen exchange and mass spectrometry. I. A generalized model for a two-state protein and comparison with experiment. Protein Sci., 2005, 14, 543-557

I.A. Kaltashov. Probing protein dynamics and function under native and mildly denaturing conditions with hydrogen exchange and mass spectrometry. Int. J. Mass Spectrom., 2005, 240, 249-259

I.A. Kaltashov, S.J. Eyles, H. Xiao. Combination of protein hydrogen exchange and tandem mass spectrometry as an emerging tool to probe protein structure, dynamics and function.  In: Focus on Protein Research.  J.W. Robinson, ed. Hauppauge, New York: Nova Science Publishers, Inc., 2004, pp. 191-218

M. Zhang, D.R. Gumerov, A.B. Mason, I.A. Kaltashov. Indirect detection of protein-metal binding: Interaction of serum transferrin with In3+ and Bi3+. J. Am. Soc. Mass Spectrom., 2004,15, 1658-1664

J.K. Hoerner, H. Xiao, A. Dobo, I.A. Kaltashov. Is there hydrogen scrambling in the gas phase? Energetic and structural determinants of proton mobility within protein ions. J. Am. Chem. Soc., 2004, 126, 7709-7717

W.P. Griffith, I.A. Kaltashov. Highly asymmetric interactions between globin chains during hemoglobin assembly revealed by electrospray ionization mass spectrometry. Biochemistry, 2003, 42, 10024-10033

A. Mohimen, A. Dobo, J.K. Hoerner, I.A. Kaltashov. A chemometric approach to detection and characterization of multiple protein conformers in solution using electrospray ionization mass spectrometry. Anal. Chem., 2003, 75, 4139-4147

H. Xiao, S.J. Eyles, I.A. Kaltashov. Indirect assessment of small hydrophobic ligand binding to a model protein using a combination of ESI MS and HDX/ESI MS. J. Am. Soc. Mass Spectrom., 2003, 14, 506-515

I.A. Kaltashov, S.J. Eyles. Studies of biomolecular conformations and conformational dynamics with mass spectrometry. Mass Spectrom. Rev., 2002, 21, 37-71

A. Dobo, I.A. Kaltashov. Detection of multiple protein conformational ensembles in solution via deconvolution of charge state distributions in ESI MS. Anal. Chem., 2001, 73, 4763-4773

D. Gumerov, I.A. Kaltashov. Dynamics of iron release from transferrin N-lobe studied by electrospray ionization mass spectrometry. Anal. Chem., 2001, 73, 2565-2570