Dmitri Kudryashov received his MD from the Russian Medical State University (RGMU) in Moscow and PhD from the Russian Academy of Medical Sciences and Cardiology Research Center, where he studied the function of the Myosin Light Chain Kinase (MLCK) family of proteins. Dmitri continued his research on the actin and myosin cytoskeleton as a postdoctoral fellow at UCLA - in Prof. Emil Reisler’s group. For his postdoctoral work, Dr. Kudryashov received the Paul Boyer Award for Outstanding Postdoctoral Studies in Biochemistry and Herbert Newby McCoy Award. Dr. Kudryashov has joined the Department of Biochemistry at OSU and will commence his work there in April of 2011.

Actin is a major component of the cytoskeleton and one of the most conserved, abundant, and functionally versatile proteins on our planet. Actin serves as a track for myosin motor motility and thus is involved in muscle contraction, organelle transport, and tightening of the contractile ring. In addition, the dynamic polymerization of actin has motor properties on its own and as such is involved in exo- and endocytosis, cell migration, division, invasion of cancer cells, and other events. Together with hundreds of actin binding proteins (ABP), actin is involved in the formation of numerous structural elements of the cell: contractile ring, stress fibers, philo- and lamellopodia, microvilli of intestinal epithelium, stereovilli of inner ear cells, and many others. Not surprisingly, many pathological events in the human body are related to actin-linked processes. Our general area of interest is the structure-function aspects of actin dynamics and its interactions with actin binding proteins in health and disease. Initially, our interests will focus in the following areas:

• As a target for many proteins and small molecule toxins produced by bacterial and viral pathogens, actin is intrinsically involved in the pathogenesis of infectious diseases. We will seek an in-depth understanding of the molecular and cellular mechanisms underlying the hijacking of the host cell actin cytoskeleton by pathogenic toxins.
• Heart diseases are among the most devastating human pathological disorders. Myosin Light Chain Kinase (MLCK), the actin and myosin binding protein, has been recently identified in failing hearts as one of the proteins, whose gene expression correlates strongly with the severity of the disease. Our goal is to elucidate how cardiac specific MLCK and other actin binding proteins affect the function and assembly of cardiomyocyte sarcomeres.
• A comprehensive understanding of the role of actin in the organization of cellular organelles is limited by the lack of tools for selective actin manipulation in cells. Therefore, our next goal is to develop and utilize tools for specific targeting of the actin cytoskeleton inside or in immediate proximity to various subcellular compartments (e.g. nucleus, Golgi, ER, etc).

In order to accomplish our goals we employ highly interdisciplinary biochemical, biophysical, and cell biology approaches, including but not limited to methods of fluorescence spectroscopy and imaging, calorimetry, chemical and enzymatic cross-linking, mass spectrometry, electron microscopy, DNA and siRNA transfection and many others. We also collaborate extensively with X-ray crystallography, NMR, and computational biology groups.

Because our lab is in the process of active growth and development, prospective graduate and undergraduate students are highly encouraged to join us. Your bright and open minds, innovative ideas, and skilled hands will find a welcome home in our group whether you are a graduate student in search for a project or an undergrad who is seeking to gain laboratory skills and contribute to solving important biological problems.

Kudryashov, D.S., Grintsevich, E.E., Rubenstein, P.A., Reisler, E. (2010) A nucleotide state-sensing region on actin. J Biol Chem. 285(33):25591-601.

Kudryashov, D.S., Durer, Z.A., Ytterberg, A.J., Sawaya, M.R., Pashkov, I., Yeates, T.0., Ogorzalek Loo, R., Loo, J., Satchell, K.J., Reisler, E. (2008) Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin. Proc Natl Acad Sci USA. 105(47):18537- 42.

Kudryashov, D.S., Cordero, C.L., Reisler, E., Satchell, KJ. (2008) Characterization of the enzymatic activity of the actin cross-linking domain from the Vibrio Cholerae MART toxin. J Biol Chem. 4;283(1):445-52.

Sawaya, M.R., Kudryashov, D.S., Pashkov, I., Reisler, E., Yeates, T.O. (2008) Mapping the interface between subunits in the actin filament using crystal structures of actin dimers ActaCrystallographica Section D. 64:454-65 4.

Kudryashov, D.S., Galkin, V.E., Orlova, A., Phan, M., Egelman, E.H., Reisler, E. (2006) Cofilin cross-bridges adjacent actin protomers and replaces part of the longitudinal F-actin interface. J Mol Biol. 358(3):785-97.

Kudryashov, D.S., Sawaya, M.R., Adisetiyo, H., Norcross, T., Hegyi, G., Reisler, E., Yeates, T.O. (2005) The crystal structure of a cross-linked actin dimer suggests a detailed molecular interface in Factin. Proc Natl Acad Sci U S A. Sep 102(37):13105-10.

Kudryashov, D.S., Phillips, M., Reisler, E. (2004) Formation and destabilization of actin filaments with tetramethylrhodamine-modified actin. Biophys J. 87(2):1136-45

Kudryashov, D.S., Stepanova, O.V., Vilitkevich, E.L., Nikonenko, T.A., Nadezhdina, E.S., Shanina, N.A., Lukas, T.J., Van Eldik, L.J., Watterson, D.M., Shirinsky, V.P. (2004) Myosin light chain kinase (210 kDa) is a potential cytoskeleton integrator through its unique N-terminal domain. Exp Cell Res. 298(2):407-17

Kudryashov, D.S., Reisler, E. (2003) Solution Properties of tetramethylrhodamine modified G-actin. Biophys J. 85(4):2466-75

Kudryashov, D.S., Vorotnikov A.V., Dudnakova, T.V., Stepanova, O.V., Lukas, T.J., Sellers, J.R., Watterson, D.M., Shirinsky, V.P. (2002) Smooth Muscle myosin filament assembly under control of a kinase-related protein (KRP) and caldesmon. J Muscle Res Cell Motil. 23(4):341-51.

Kudryashov, D.S., Chibalina, M.V., Birukov, K.G., Lukas, T.J., Sellers, J.R., Van Eldik, L.J., Watterson, D.M., Shirinsky, V.P. (1999) Unique sequence of a high molecular weight myosin light chain kinase is involved in interaction with actin cytoskeleton. FEBS Lett. 463, 67-71.