Anushka Michailova

Anushka Michailova, Ph.D. (1952-2014)

Associate Project Scientist

My research focuses on using mathematical methods to model and better understand cardiac muscle cells; delineating Ca2+ mediated signaling, excitation-contraction coupling, excitation-transcription coupling, and energy metabolism. These studies have the common theme of developing mathematical models in terms of ordinary and partial differential equations, numerical methods, and dynamic systems analysis in order to solve problems. In the long-term, these types of systems analyses at the cellular level will be important for developing an organ- and system-level understanding of the heart and cardiovascular system, in health and disease.

Refereed journal papers

Hohendanner F, McCulloch A, Blatter LA, Michailova A. (2014) Calcium and IP3 dynamics in cardiac myocytes: Experimental and computational perspectives and approaches. Frontiers in Pharmacology of Ion Channels and Channelopathies: CaMKII in Cardiac Health and Disease (accepted)

Kekenes-Huskey PM, Liao T, Gillette AK, Hake JE, Zhang Y, Michailova AP, McCulloch AD, McCammon JA (2013) Molecular and sub cellular-scale modeling of nucleotide diffusion in the cardiac myofilament lattice Biophys J 105(9):2130-2140.

Lo YH, Peachey T, Abramson D, IMcCulloch A, Michailova A. (2013) Sensitivity of rabbit ventricular action potential and Ca2+ dynamics to small variations in membrane currents and ion diffusion coefficients. Bio Med Res Int 2013:565431.

Liao T, Y Zhang, Kekenes-Huskey P, Cheng Y, Michailova A, Holst M, McCammon JA (2013) Efficient Computation in Multiscale Geometric Modeling for Biomolecular Complexes. Molecular Based Math Biol 1:164-179.

Kekenes-Huskey P, Cheng Y, Hake J, Sachse F, Bridge J, Holst M, McCammnon A, McCulloch A, Michailova AP (2012) Modeling effects of L-type Ca2+ current and Na+-Ca2+ exchanger on Ca2+ trigger flux in rabbit myocytes with realistic t-tubule geometries. Frontiers in Computational Physiology and Medicine: Calcium Signaling in Cardiac Myocytes 3:351.

Tveito A, Lines GT, Edwards AG, Maleckar MM, Michailova AP, Hake J, McCulloch AD (2012) Slow calcium-depolarization-calcium waves may initiate fast local depolarization waves in ventricular tissue. Prog Biophys Molec Biol 110(2-3):295–304.

JE Hake, AG Edwards, Z Yu, P Kekenes-Huskey, AP Michailova, A McCammon, MJ Holst, M Hoshijima, AD McCulloch (2012) Modeling Cardiac Calcium Sparks in a Three-Dimensional Reconstruction of a Calcium Release Unit, Journal Physiology 590(18): 4403-4422.

Y Cheng, P Kekenes-Huskey, J Hake, MJ Holst, JA McCammon, AP Michailova. Multi-Scale Continuum Modeling of Biological Processes: From Molecular Electro-Diffusion to Sub-Cellular Signaling Transduction. Computational Science & Discovery, 5: 015002 (14pp),2012.

Frangi AF, Coatrieux JL, Peng GC, D’Argenio DZ, Marmarelis VZ, Michailova A. Editorial: special issue on multiscale modeling and analysis in computational biology and medicine-part-2. IEEE Trans Biomed Eng. Eng.58(12):3434-3439, 2011.

Z Yu, G Yao, M Hoshijima, A Michailova, M Holst. Multi-Scale Modeling of Calcium Dynamics in Ventricular Myocytes with Realistic Transverse Tubules, IEEE TBME Letters, Spatial Issue on “Multi-Scale Modeling and Analysis for Computational Biology and Medicine”; 58(10):2947-2951, 2011.

Frangi AF, Coatrieux JL, Peng GC, D’Argenio DZ, Marmarelis VZ, Michailova A. Editorial: special issue on multiscale modeling and analysis in computational biology and medicine-part-1. IEEE Trans Biomed Eng.58(10):2936-2942, 2011.

Cheng Y, Yu Z, Hoshijima M, Holst M, McCulloch A, McCammon JA, and Michailova A. Effects of 3D t-tubule anatomy on Ca2+ signaling in rodent ventricular myocytes with inhibited sarcoplasmic reticulum. PLoS Computational Biology, 6(10), article e1000972, 2010.

Abramson D, Bethwaite B, Enticott C, Garic S, Peachey T, Michailova A, and Amirriazi S. Embedding Optimization Computational Science Workflows. Journal of Computational Science, 1: 41-47, 2010 (invited paper).

Abramson D, Bethwaite B, Enticott C, Garic S, Peachey T, Michailova A, and Amirriazi S. Automatic Design Optimization using Parallel Workflows. Procedia Computer Science, 1:2159-2168, 2010.

Abramson D, Bethwaite B, Enticott C, Garic S, Peachey T, Michailova A, Amirriazi S, and Chitters R. Robust Workflows for Science and Engineering, ACM MTAGS09,, 2009.

Lu S, Michailova A, Saucerman JJ, Cheng Y, Yu Z, Kaiser T, Li W, Banks RE, Holst M, McCammon JA, Hayashi T, Hoshijima M, Arzberger P, and McCulloch AD. Multi-Scale Modeling in Rodent Ventricular Myocytes: Contributions of structural and functional heterogeneities to excitation-contraction coupling. IEEE Engineering in Medicine and Biology, 28(2):46-57, 2009.

Peachey TC, Diamond NT, Abramson D, Sudholt W, Michailova A, Amirriazi S. Fractional Factorial Design for Parameter Sweep Experiments using Nimrod/E, Journal of Scientific Programming, 16(2,3):217-230, 2008.

Michailova A and McCulloch AD. Effects of Mg2+, pH and PCr on cardiac excitation-metabolic coupling, Magnesium Research, 21(1):16-28, 2008.

Michailova A, Lorentz W, and McCulloch AD. Modeling transmural heterogeneity of KATP current in rabbit ventricular myocytes. AJP Cell Physiology, 293:542-557, 2007.

Li WW, Baker N, Baldridge K, McCammon A, Ellisman MH, Gupta A, Holst M, McCulloch A, Michailova A, Papadopoulos Ph, Olson A, Sanner M, and Arzberger PW. National Biomedical Computation Resource (NBCR): Developing End-to-End Cyberinfrastructure for Multiscale Modeling in Biomedical Research, CTWatch QUARTERLY, 2(3):6-17, 2006.

Michailova A, Saucerman J, Belik ME, and A McCulloch. Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP and Mg2+. Biophysical Journal, 88:2234-2249, 2005.

Michailova A, Belik ME, and A McCulloch. Effects of magnesium on cardiac excitation-contraction coupling. Journal of the American College of Nutrition, 23: 514S-517S, 2004.

Saucerman J, Brunton L, Michailova A, and A McCulloch. Modeling beta-adrenergic control of cardiac myocyte contractility in silico. Journal Biological Chemistry, 278:47997-48003, 2003.

Zhang H, Noble D, Cannell M, Orchard C, Lancaster M, Boyett M, Holden A, Jafri M, Sobie E, Lederer W, Demir S, Michailova A, DelPrincipe F, Egger M, Niggli E, Smith G, Loughrey C, MacQuaide N, Dempster J, and A Trafford. Dynamics of cardiac intracellular Ca2+ handling – from experiments to virtual cells. International Journal of Bifurcation and Chaos 13(12):3535-3560, 2003.

Michailova A, F DelPrincipe, M Egger, and E Niggli. Spatiotemporal features of Ca2+ signaling, buffering and diffusion in atrial myocytes with inhibited sarcoplasmic reticulum. Biophysical Journal, 83: 3134-3151, 2002.

Michailova A and A McCulloch. Model Study of ATP and ADP buffering, transport of Ca2+ and Mg2+, and regulation of ion pumps in ventricular myocyte. Biophysical Journal, 81: 614-629, 2001.

Michailova A. Modeling of the dependence of the isometric tension on the stimulation frequency and the action potential duration in cardiac muscle. Comptes Rendus de l’Academie Bulgare des Sciences 50, No4: 101-104, 1997.

Michailova A and V Spassov. Computer simulation of excitation-contraction coupling in cardiac muscle. A study of the regulatory role of calcium binding to troponin C. General Physiology and Biophysics 16(1): 29-38, 1997.

Michailova A. and V Spassov. Theoretical model and computer simulation of excitation-contraction coupling of mammalian cardiac muscle. Journal of Molecular and Cellular Cardiology 24: 97-104, 1992.

Michailova A and N Petrov. Mechano-mathematical model of excitation-contraction coupling in muscle tissue. Biorheology, Suppl. I: 209-212, 1984.

Petrov N, Michailova A, and V Jupanov. Thermodynamical model of deformable semi-conductor. Theoretical and Applied Mechanics, Sofia, Bulgaria, Year IX, No1: 42-46, 1978.

Book chapters

Michailova AP, Edwards AG, Hake J, Hoshijima M, McCulloch AD (2012) Calcium Signaling in Cardiomyocyte Models with Realistic Geometries, CARDIAC ELECTROPHYSIOLOGY: From Cell to Bedside (book chapter) (accepted)