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Igor Kaltashov

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

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

N369 Life Sciences Laboratory
413-545-1460

kaltashov[at]chem.umass.edu


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.