Research Assistant Professor of Biomedical Engineering
Most of the research designed for new drug testing and disease studies utilizes in vivo animal models or in vitro human cells cultured in a two-dimensional environment. Advances in tissue engineering and new organs-on-chips and human induced pluripotent stem cell (iPSC) technologies offer great possibilities to better simulate the physiological and mechanical in vivo environment and more accurately replicate the physiology of various human cell types in vitro in normal and pathologic conditions.
My current research efforts are focused on the role of the mechanistic target of rapamycin (mTOR) pathway in the pathogenesis of tuberous sclerosis complex (TSC) in a heart-on-a-chip model. In the heart, TSC is characterized by abnormal growth of cardiac tissue, cardiac rhabdomyomas, and arrhythmias. In particular, we are investigating the mechano-elastic and genetic changes induced by inhibition of mTOR in cardiac tissue constructs, engineered using normal iPSCs and iPSCs bearing a loss-of-function mutation in the TSC2 gene.
Another research interest is the development of an organ-on-chip model of aortic aneurysm disease. This pathology is characterized by progressive degeneration of the aortic wall, usually not associated with trauma, infection, or genetic mutation. Vascular smooth muscle cells (VSMCs) have remarkable plasticity in switching between contractile and synthetic phenotypes. It is considered that this process is involved in aneurysmal changes in the aorta. In VSMCs, mTOR regulates a variety of functions, including differentiation, metabolism, and energy status. We believed that mTOR signaling may determine VSMC phenotype and play a key role in aorta pathogenesis.
- Roth B.J., Sidorov V.Y., Wikswo J.P. “Virtual Electrode Theory of Pacing,” in Cardiac Bioelectric Therapy: Mechanisms and Practical Implications, 2nd edition, Efimov IR, Ng FS, Laughner JI, Eds., Springer Nature, 147-179, 2021.
- Sulgin A.A., Sidorova T.N., Sidorov V.Y. Growth and characterization of a tissue-engineered construct from human coronary artery smooth muscle cells. Bulletin of Siberian Medicine. v.19(2), 85-95, 2020.
- Sidorov V.Y., Samson P.C., Sidorova T.N., Davidson J.M., Lim C.C., Wikswo J.P. I-Wire heart-on-a-chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology. Acta Biomater., v48, 68-78, 2017.
- Schroer A.K., Shotwell M.S., Sidorov V.Y., Wikswo J.P., Marryman D.W. I-Wire heart-on-a-chip II: Biomechanical analysis of contractile, three-dimensional cardiomyocyte tissue constructs. Acta Biomater., v.48, 79-87, 2017.
- Drake K.J., Shotwell M.S., Wikswo J.P., Sidorov V.Y. Glutamine and glutamate increase action potential duration in anoxia-challenged hearts. Physiological Reports, v.3(9), 1-9, 2015.
- Shotwell M.S., Drake K.J., Sidorov, V.Y., Wikswo J.P. Mechanistic analysis of challenge-response experiments. Biometrics, v.69(3), 741-747, 2013.
- Gray R.A., Mashburn D.N., Sidorov V.Y., Roth B.J., Wikswo J.P. Transmembrane current imaging during pacing and fibrillation. Biophys.J., v.105, 1710-1719, 2013.
- Woods M.C., Uzelac I., Holcomb M.R., Wikswo J.P., Sidorov V.Y. Diastolic field stimulation: the role of shock duration in epicardial activation and propagation. Biophys. J., v.105, 523-532, 2013.
- Gray R.A., Mashburn D.N., Sidorov V.Y., Wikswo J.P. Quantification of transmembrane currents during action potential propagation in the heart. Biophys.J., v.104, 268-278, 2013.
- Potet F., Loric A., Chaigne S., Hopkins C., Lewis M., Venkataraman R., Sidorov V., Engers D., Zhou B., Balser J.R., Li M., Baudenbacher F., Lindsley C., Weaver D., Kupershmidt S. Identification and characterization of a compound that protects cardiac tissue from hERG-related, drug-induced arrhythmias. Journal of Biological Chemistry, v.287, 39613-39625, 2012.
- Sidorov V.Y., Uzelac I., Wikswo J.P. Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution. Am. J. Physiol. Heart Circ. Physiol., v. 301, H209-H220, 2011.
- Holcomb M.R., Devine J., Harder R., Sidorov V.Y. Continuous-waveform constant-current isolated physiological stimulator. Rev. Sci. Instrum., v.83(4), 044303, 2012.