Profile: Svetlana Tikunova

Svetlana Tikunova
Svetlana Tikunova, Ph.D.
Assistant Professor of Pharmacology
Department of Pharmacological and Pharmaceutical Sciences
UH College of Pharmacy
521 Science and Research Building 2, room 542 A
Houston TX 77204-5037

713-743-1224
713-743-1884 (fax)
sbtikunova@uh.edu

Education

B.S., Biophysics Program, St. Petersburg State Technical University, St. Petersburg, Russia
Ph.D., Biophysics Graduate Program, The Ohio State University, Columbus, OH
Postdoctoral, Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH

Research Interests

My current research goals are to understand the basic mechanisms that control cardiac muscle contraction and relaxation. My ultimate goal is to rationally engineer proteins that could be used to treat heart disease. Heart failure is one of the leading causes of death in developed countries. Diastolic dysfunction (impaired cardiac muscle relaxation) occurs in up to 40% heart failure patients. Cardiac relaxation is not merely a passive reversal of contraction, but a complex process that involves a series of events, one of which is dissociation of calcium from troponin C. The role of troponin C in the process of cardiac relaxation is controversial and not well understood. I am particularly interested in understanding if altering the calcium dissociation from troponin C can influence the rate of cardiac muscle relaxation. By directly modifying the rate of calcium dissociation from troponin C and examining what effect it has on muscle relaxation, I can define the role of troponin C in relaxation of skinned and intact cardiac trabeculae. To achieve these goals I utilize a variety of biochemical and physiological approaches.

Research Grants

National Institutes of Health (NIH) K99 Award: Influence of troponin C on the rate of cardiac muscle relaxation. 2008 - 2012

Selected Publications

Journal Articles

Liu B, Tikunova SB, Kline KP, Siddiqui JK, Davis JP. Disease-related cardiac troponins alter thin filament ca(2+) association and dissociation rates. PLoS One. 2012;7(6):e38259.

Liu B, Lee RS, Biesiadecki BJ, Tikunova SB, Davis JP. Engineered Troponin C Constructs Correct Disease-related Cardiac Myofilament Calcium Sensitivity. J Biol Chem. 2012 Jun 8;287(24):20027-36.

Albury AN, Swindle N, Swartz DR, Tikunova SB. Effect of hypertrophic cardiomyopathy-linked troponin C mutations on the response of reconstituted thin filaments to calcium upon troponin I phosphorylation. Biochemistry. 2012 May 1;51(17):3614-21.

Little SC, Tikunova SB, Norman C, Swartz DR, Davis JP. Measurement of calcium dissociation rates from troponin C in rigor skeletal myofibrils. Front Physiol. 2011;2:70.

Lee RS, Tikunova SB, Kline KP, Zot HG, Hasbun JE, Van Minh N, Swartz DR, Rall JA, Davis JP. Effect of the Ca2+ Binding Properties of Troponin C on the Rate of Skeletal Muscle Force Redevelopment. Am J Physiol Cell Physiol. 2010 Nov;299(5):C1091-9.

Swindle N, Tikunova SB. Hypertrophic cardiomyopathy-linked mutation D145E drastically alters calcium binding by the C-domain of cardiac troponin C. Biochemistry. 2010 Jun 15;49(23):4813-20.

Tikunova SB, Liu B, Swindle N, Little SC, Gomes AV, Swartz DR, Davis JP. Effect of calcium-sensitizing mutations on calcium binding and exchange with troponin C in increasingly complex biochemical systems. Biochemistry. 2010 Mar 9;49(9):1975-84.

Liang, B., Chung, F., Qu, Y., Pavlov, D., Gillis, T. E., Tikunova, S. B., Davis, J. P. and Tibbits, G. F. (2008). Familial hypertrophic cardiomyopathy-related cardiac troponin C mutation L29Q affects Ca2+ binding and myofilament contractility. Physiol. Genomics 33: 257-266.

Davis, J. P. and Tikunova, S. B. (2008). Ca2+ exchange with troponin C and cardiac muscle dynamics. Cardiovasc. Res. 77: 619-626.

Norman, C., Rall, J.A., Tikunova, S. B. and Davis, J. P. (2007). Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities. Am. J. Physiol. Heart Circ. Physiol. 293: H2580-2587.

Kreutziger, K.L., Gillis, T.E., Davis, J. P., Tikunova, S.B. and Regnier, M. (2007). Influence of enhanced troponin C Ca2+-binding affinity on cooperative thin filament activation in rabbit skeletal muscle. J. Physiol. 583: 337-350.

Engel, P. L., Kobayashi, T., Biesiadecki, B., Davis, J., Tikunova, S., Wu, S. and Solaro, R. J. (2007). Identification of a region of troponin I important in signaling cross-bridge-dependent activation of cardiac myofilaments. J. Biol. Chem. 282: 183-193.

Davis, J.P., Norman, C., Kobayashi, T., Solaro, R.J., Swartz, D.R. and Tikunova, S.B. (2007). Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C. Biophys. J. 92: 3195-3206.

Swartz, D. R., Yang, Z., Sen, A., Tikunova, S. B. and Davis, J. P. (2006). Myofibrillar troponin exists in three states and there is signal transduction along skeletal myofibrillar thin filaments. J. Mol. Biol. 361: 420-435.

Fidalgo da Silva, E., Freire, M. M., Barrabin, H., Sorenson, M. M., Tikunova, S., Johnson, J. D., Chandra, M., Pearlstone, J. R. and Scofano, H. M. (2006). Troponin C/calmodulin chimeras as erythrocyte plasma membrane Ca2+-ATPase activators. Int. J. Biochem. Cell Biol. 38: 209-221.

Book Chapters

Luo, Y., Davis, J.P., Tikunova, S.B., Smillie, L.B., and Rall, J.A.  Myofibrillar determinants of rate of relaxation in skinned skeletal muscle fibers.  In Molecular and  Cellular Aspects of Muscle Contraction.  H. Sugi, ed., Kluwer Academic/Plenum Publishers, New York, 538: 573-582, 2003.

Johnson, J.D., and Tikunova, S.B.  Fluorescence methods for measuring calcium affinity and calcium exchange with proteins. Methods Mol. Biol. 173: 89-102, 2002.

Presentations & Abstracts

Tikunova, S.B., and Swindle, N.  Effect of D145E mutation on calcium binding and exchange with the C-domain of troponin C. Biophys J. (Abstracts): 150a, 2010

Liu, B., Lee, R.S., Rall, J.A., Tikunova, S.B., and Davis, J. P. Abnormal thin filament calcium binding associated with cardiac muscle diseases can be corrected through TnC mutagenesis. Biophys. J. (Abstracts): 356a, 2010.

Liu, B., Little, S.C., Lee, R.S., Kline, K.P., Swartz, D.R., Tikunova, S.B., and Davis, J. P.  The rate of calcium dissociation from the cardiac thin filaments is affected by multiple modulatory factors. Biophys. J. (Abstracts):A503, 2009.

Tikunova, S., Liu, B., Potter, J.D., Gomes, A.V., Swartz, D. R., and Davis, J.P. Designing troponin C mutants with dramatically altered calcium dissociation rates in complex biochemical systems. Biophys. J. (Abstracts): 651pos, 2008.

Liang, B., Chung, F., Tikunova, S.B., Davis, J.P., and Tibbits, G.F. The familial hypertrophic cardiomyopathy related cardiac troponin C mutation, L29Q, and its nearby N-terminal  mutations increase Ca2+ binding affinity and myofilament Ca2+ sensitivity. Biophys. J. (Abstracts): A638, 2007.

Tikunova, S.B., Swartz, D.R., and Davis, J.P. Sensitizing cardiac troponin to calcium through troponin I. Biophys. J. (Abstracts): A629, 2007.

Norman, C., Rall, J.A., Tikunova, S.B., and Davis, J.P. Thin filament calcium sensitivity modulates the rate of cardiac contraction by altering the fractional force.  Biophys. J.     (Abstracts): A477, 2007. 

Engel, P.L., Kobayashi, T., Biesiadecki, B.J., Wu, S., Davis, J.P., Tikunova, S.B., and Solaro, R.  J.  An N-terminal region surrounding Ala 66 in cardiac troponin I is critical in signaling cross-bridge dependent activation.  Biophys. J. (Abstracts): A337, 2006.

Tikunova, S.B., Alionte, C., Gomes, A., Potter, J.D., Rall, J.A., and Davis, J.P.  Effect of cardiac troponin C mutations on calcium binding and exchange with the troponin complex and muscle force generation.  Biophys. J. (Abstracts): A117-118, 2006.

Davis, J.P., Tikunova, S.B.,  Kobayashi, T., Alionte, C., Warren, C.M., Rall, J.A. and Solaro, R. J.   Thin and thick filament proteins affect Ca2+ binding and exchange with cardiac troponin C. Biophys. J. (Abstracts): A117, 2006.