M.S. Molecular Biophysics and Applied Physics & Mathematics, Moscow
Institute of Physics and Technology, 1990.
Ph.D. Molecular & Cellular Pharmacology, State University of New
York, Stony Brook, 2000.
Adjunct Assistant Professor, Massachusetts College of Pharmacy and
I investigate how structure and dynamics of proteins interplay with their biological function. Currently, I study the structure/dynamics properties of cytoskeleton-regulating proteins which consist of multiple structured domains (modules). Many of such modular proteins are capable of altering their roles in response to cell signals by repositioning the domains relatively to each other while each individual domain remains structurally unperturbed. Multi-domain proteins constitute the majority of human proteome yet their very flexibility and capacity to rearrange often prevent their structural characterization by most techniques (e.g. x-ray crystallography). Methods I specialize in (especially Nuclear Magnetic Resonance spectroscopy or NMR) combined with general biochemical approaches deliver site-specific information about the structure, dynamics and function of modular proteins. I am especially interested in deciphering the roles of the inter-domain linkers by understanding how their length, residue composition and backbone dynamics relate to the function of the corresponding modular proteins.
The other major focus of my research is the biophysical properties of DNA with chemical modifications of the bases. Chemical modifications of genomic DNA have principal roles in both natural gene regulation and DNA damage. In the cell, gene activity is regulated via enzymatic modification of cytosine (methylation). Cytosine modification rates are vital as their alteration can compromise cell function and organism survival. Unlike this modification of cytosine, which serves a regulatory role, modifications of guanine (oxidation) may be detrimental to the integrity of the genetic information. Left unrepaired, these common types of guanine damage (lesion) can lead to genome instability and mutations. In the human genome, there are many occurrences of cytosine and guanine being adjacent (clustered). Repair of a guanine lesion neighboring a modified cytosine is known to be compromised. Likewise, normal cytosine modification rates are altered within the sites containing a modified guanine. The chemical reasons for these adverse enzymological effects have yet to be determined. One of the missing links is the characterization of DNA with modified guanine and cytosine clustered together. To close this gap, I investigate the fundamental biophysics (stability, structure and dynamics) of DNA with guanine lesions adjacent to modified cytosines. Such a comprehensive studies of linked damage and regulatory modifications in DNA is being performed for the first time, pioneering new research in genome stability and regulation.
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