Tatiana Kostrominova, Ph.D.

Education

• Ph.D. in Cell Biology, Institute of Cytology Russian Academy of Sciences, St. Petersburg, Russia, 1991
• Postdoctoral Fellow, University of Connecticut, Farmington, 1992-1994
• Postdoctoral Research Associate, Washington University, Saint Louis, 1994-1998
• Postdoctoral Fellow, University of Michigan, Ann Arbor, 1998-2005
• Research Investigator, University of Michigan, Ann Arbor, 2005-2006

Memberships

• The American Physiological Society, 2003 to present

Research Interest

The main focus of my research is to study changes of gene and protein expression in skeletal muscle during denervation and aging and their effect on the decline of muscle functional activity. One of the features of skeletal muscles of old animals is spontaneous denervation of some of the muscle fibers. The number of denervated fibers shows a progressive increase with advanced age. Increased denervation of fibers leads to muscle atrophy, weakness and loss of physiological functions. Recently, I concluded a study of genes differentially expressed in experimentally denervated skeletal muscles of rats using the Gene Array method (Kostrominova et al., 2005).

My future research plans for this study include elucidating the molecular mechanisms regulating expression of genes after denervation utilizing techniques that evaluate the activation of signaling cascades and promoter constructs. The goal is to identify mechanisms of gene regulation that are critical for the prevention of skeletal muscle functional decline after denervation.

A large part of my research is devoted to the role of reactive oxygen species (ROS) in the development of skeletal muscle pathology with advanced age. Oxidative damage to DNA, proteins and lipids plays an important role in the decreased function of skeletal muscles during aging. I am using superoxide dismutase 1 knockout mice as a model for elucidating mechanisms regulating structural changes and gene expression patterns in skeletal muscles of young and old mice (Kostrominova et al., 2007). The results of this study could enhance understanding of the mechanisms responsible for the decline of skeletal muscle function at an old age.

I am also interested in studies on the effect of obesity and aging on skeletal muscles of rhesus monkeys, Zucker rats and Ossabaw pigs. We showed previously that in rhesus monkeys the obesity was associated with a decline in fast oxidative fibers in vastus lateralis muscles during aging. In future studies I will be evaluating age- and /or obesity associated changes in gene expression in skeletal muscles of rats, Ossabaw pigs and rhesus monkeys.

In collaboration with Lisa Larkin and Ellen Arruda from the University of Michigan I work on the tissue engineering of the nerve-muscle-tendon constructs in vitro (Larkin et al., 2007). This is a very exciting and promising area of research allowing implementation of the engineered nerve-muscle-tendon constructs as a model for the developmental biology, experimental pharmacology, and for in vivo tissue replacement of the diseased or damaged muscles, tendons and nerves.

Lab Personnel

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  • Brad Clark, undergraduate student, Purdue University Calumet

Collaborators

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  • Lisa Larkin, University of Michigan
  • Ellen Arruda, University of Michigan
  • John Faulkner, University of Michigan
  • Pat McDonough, Vala Sciences Inc
  • Doug Dow, Myo Clinic
  • Michael Sturek, Indiana University

Publications

Selected Peer-reviewed publications

Kostrominova, T.Y., Pasyk, K.A., Van Remmen, H., Richardson, A.G., and Faulkner, J.A. (2007) Adaptive changes in structure of skeletal muscles from adult Sod1 homozygous knockout mice. Cell Tissue Res 327: 595-605.

Larkin L.M., Calve s., Kostrominova, T.Y., Arruda E.M. (2007) Structure and Functional Evaluation of Tendon-Skeletal Muscle Constructs Engineered in Vitro. Tissue Engineering, In print

Kostrominova, T.Y., Dow, D.E., Dennis, R.G., Miller, R.A., and Faulkner, J.A. (2005) Comparison of Gene Expression of Two-Month Denervated, Two-Month Denervated-Stimulated and Control Rat Skeletal Muscles. Physiol. Genomics 22: 227-243.

Dow, D.E., Cederna, P.S., Hassett, C.A., Kostrominova, T.Y., Faulkner, .JA., and Dennis, R.G. (2004) Number of Contractions to Maintain mass and Force of a Denervated Rat Muscle. Muscle Nerve 30: 77-86.

Dedkov*, E.I., Kostrominova*, T.Y., Borisov, A.A., and Carlson, B.M. (2003) MyoD and Myogenin Protein Expression in Skeletal Muscles of Senile Rats. Cell Tiss. Res. 311: 401-416 .*authors had equal contribution to this manuscript.

Carlson, B.M., Borisov, A.A., Dedkov, E.I., Dow, D., and Kostrominova, T.Y. (2002) The Biology and Restorative Capasity of Long-Term Denervated Skeletal Muscle. Basic Appl. Myol. 12: 247-254.

Carlson, B.M., Borisov, A.A., Dedkov, E.I., Khalyfa, A., Kostrominova, T.Y., Macpherson, P., Wang, E., and Faulkner, J.A. (2002) Effect of Long-Term Denervation on Skeletal muscle in Old Rats. J. Gerontol. 57A: B366-374.

Macpherson, P., Kostrominova, T.Y., Tang, H., and Goldman, D. (2002) Protein Kinase C and Calcium/Calmodulin-activated Protein Kinase II (CaMKII) Suppress Nicotinic Acetylcholine Receptor Gene Expression in Mammalian Muscle. A Specific Role for CaMKII in Activity-Dependent Gene Expression. J. Biol. Chem. 277: 15638-15646.

Dedkov, E.I., Kostrominova, T.Y., Borisov, A.A., and Carlson, B.M. (2002) Survival of Schwann Cells in Chronically Denervated Skeletal Muscles. Acta Neuropathol. 103: 565-574.

Dedkov, E.I., Kostrominova, T.Y., Borisov, A.A., and Carlson, B.M. (2002) Resistance Vessel Remodeling and Reparative Angiogenesis in the Microcirculatory Bed of Long-Term Denervated Skeletal Muscles. Microvasc. Res. 63:96-114.

Dedkov, E.I., Kostrominova, T.Y., Borisov, A.A., and Carlson, B.M. (2001) Reparative Myogenesis in Long-Term Denervated Skeletal Muscles of Adult Rats Results in a Reduction of the Satellite Cell Population. Anat. Rec. 263:139-154.

Kostrominova, T.Y., Macpherson,P.D., Carlson, B. M., and Goldman, D. (2000) Regulation of Myogenin Protein Expression in Denervated Muscles from Young and Old Rats. Am. J. Physiology 279:R179-R188.

Kostrominova, T.Y., and Tanzer, M.L. (1995) Temporal and Spatial Appearance of ±-Dystroglycan in Differentiated Mouse Myoblasts in Culture. J. of Cell. Biochem. 58: 527-534.

Kostrominova, T.Y., and Tanzer, M.L. (1995) Rodent Myoblast Interactions With Laminin Require Cell Surface Glycoconjugates But Not Laminin Glycosyl Groups. J. Cell. Biochem. 57: 163-17