Weinberg Lab for Computational Physiology
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Weinberg Lab for Computational Physiology
Welcome to the Computational Physiology Lab!
Our lab research is focused on developing novel computational tools and methods to understand physiology and disease and develop new therapies. Our research spans a wide range of physiological areas and topics, including electrophysiology, multicellular and subcellular signaling pathways, and mechanobiology. We study healthy normal physiological functioning and diseases and pathologies, including cardiac arrhythmias, fibrosis, and cancer. In our lab, we use multiscale biophysical models and machine learning tools to study complex physiology and pathophysiology.
Computational modeling is a multidisciplinary field, combining tools from engineering, data science, biology, mathematics, physics, chemistry, and computational science. Over the past few decades, computational modeling has become an invaluable counterpart to experimental physiology and a powerful tool for predictive medicine – using models to understand and predict biological dynamics during health and disease to identify new therapies.
Cardiac electrophysiology and arrhythmias
Cardiac electrophysiology is the study of electrical signaling in the heart. We use a variety of computational modeling approaches to study how electrical signaling in cardiac cells becomes irregular and triggers arrhythmias. Using detailed physiological models, we simulate activity of action potentials, calcium transients, ion channels, and intracellular signaling molecules to study their responses in irregular rhythms, such as cardiac alternans, and in cells with mutations associated with disease, such as long QT (LQT) syndrome. We are interested in many different aspects of cardiac electrophysiology regulation, including intercellular nanodomain signaling, ephaptic coupling, intracellular calcium handling, and stochastic calcium release.
Mechanotransduction and extracellular matrix signaling
Mechanical interactions between cells and with their surrounding environment play a key role in regulating cell signaling in development, in healthy tissue and in diseases, such as cancer. We use computational models to study how cells sense and respond to these mechanical cues. In particular, we are interested in how cells assemble, interact with, and are regulated by the extracellular matrix (ECM), a web of proteins that provide structural support for cells in tissues. Using detailed biophysical models, we simulate the dynamics of ECM integrin binding, mechanical stretching, and transduction of acto-myosin generated forces to the surrounding substrate. We are interested in how these mechanical interactions regulate inter- and intracellular signaling, including fibrotic signaling pathways.
 Yu JK, Liang JA, Weinberg SH, and Trayanova NA. “Computational modeling of aberrant electrical activity following remuscularization with intramyocardially injected pluripotent stem cell-derived cardiomyocytes.” J Mol Cell Cardiol. 162: 97-109. Article
 Poelzing S, Weinberg SH, and Keener JP. “Initiation and entrainment of multicellular automaticity via diffusion limited extracellular domains.” Biophysical J. 120:1-16. Article
 Oomen PJA, Phung TN, Weinberg SH, Bilchick KC, and Holmes JW. “A rapid electromechanical model to predict reverse remodeling following cardiac resynchronization therapy.” Biomech Modeling Mechanobio. In press. Article
 Hirway SU, Lemmon CA, and Weinberg SH. “Multicellular Mechanochemical Hybrid Cellular Potts Model of Tissue Formation During Epithelial-Mesenchymal Transition.” Computational and Systems Oncology. In press
 Wu X, Hoeker GS, Blair G, King DR, Gourdie R, Weinberg SH, and Poelzing S. “Hypernatremia and intercalated disc edema synergistically exacerbate the long QT syndrome type 3 phenotype.” Am J Physiol. Heart Circ Physiol. 321(6):H1042-H1055. Article
 Nowak MB, Veeraraghavan V, Poelzing S, and Weinberg SH, “Cellular size, gap junctions, and sodium channel properties govern developmental changes in cardiac conduction.” Frontiers in Physiology. 12:731025. Article
 Veerarghavan R, Moise N, and Weinberg SH. “Sodium channels and the intercalated disk – it is all about location, location, location.” J Physiology. 599(21):4735-36. Editorial. Article
 Bogdanov V, Soltisz AM, Moise N, Ivanova M, Andreev I, Sakuta G, Weinberg SH, Davis JP, Veerarghavan R, and Gyorke S. “Distributed synthesis of sarcolemmal and sarcoplasmic reticulum membrane proteins in cardiac myocytes.” Basic Research in Cardiology. 116:63. Article
 Moise N, Struckman HL, Dagher C, Veeraraghavan R, and Weinberg SH, “Intercalated disk nanoscale structure regulates cardiac conduction.” J Gen Physiology. 153(8): e202112897. Article
 Gratz D, Winkle A, Weinberg SH, and Hund TJ. “Statistical approach to incorporating experimental variability into a mathematical model of the voltage-gated Na+ channel and human atrial action potential.” Cells. 10: 1516. Article
 Weinberg SH, Saini N and Lemmon CA. “Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.” PLoS ONE. 16(6): e0248256. Article
 Hirway S, Hassan N, Sofroniou M, Lemmon CA, and Weinberg SH, “Immunofluorescence image feature analysis and phenotype scoring pipeline for distinguishing epithelial-mesenchymal transition” Microscopy and Microanalysis. 1-11. Article
 Nowak M, Poelzing S, and Weinberg SH, “Mechanisms underlying age-associated manifestation of cardiac sodium channel gain-of-function” J Mol Cell Cardiol. 154:60-71. Article
 Link PA, Heise RL, and Weinberg SH, “Cellular mitosis predicts vessel stability in a mechanochemical model of sprouting angiogenesis” Biomech Modeling Mechanobio. doi.org/10.1007/s10237-021-01442-8. Article
 Phadumdeo VM and Weinberg SH, “Dual regulation by subcellular calcium heterogeneity and heart rate variability on cardiac electromechanical dynamics.” Chaos. 30: 093129. Article
 Comlekoglu T and Weinberg SH, “Memory in a fractional-order cardiomyocyte model alters voltage- and calcium-mediated instabilities.” Commun Nonlinear Sci Numer Simulat. Article
 Nowak MB, Greer-Short A, Wan X, Wu X, Deschenes I, Weinberg SH*, and Poelzing S*, “Intercellular sodium regulates repolarization in cardiac tissue with sodium channel gain-of-function.” Biophysical J. Article
 Scott LE, Griggs LA, Narayanan V, Conway DE, Lemmon CA, and Weinberg SH, “A hybrid model of intercellular tension and cell-matrix mechanical interactions in a multicellular geometry.” Biomech Modeling Mechanobio. Article
 Mendez MJ, Hoffman MJ, Cherry EM, Lemmon CA, and Weinberg SH, “Cell fate forecasting: a data assimilation approach to predict epithelial-mesenchymal transition.” Biophysical J. 118: 1-20. Article
 Shah C, Jiwani S, Limbu B, Weinberg SH, and Deo M, "Delayed afterpolarization-induced triggered activity in cardiac Purkinje cells mediated through cytoslic calcium diffusion waves." Physiological Reports 7(24): e14296. Article
 Nowak MB, Phadumdeo VM, and Weinberg SH, "How to boost efficacy of a sodium channel blocker: the devil is in the details." JACC: Basic to Transl Sci. 4(6) (2019). Editorial.
 Scott LE, Weinberg SH, and Lemmon CA, "Mechanochemical signaling of the extracellular matrix in epithelial-mesenchymal transition." Front. Cell Dev. Biol. (2019). Review.
 Bui J, Conway DE, Heise RL, and Weinberg SH, “Mechanochemical coupling and junctional forces in collective cell migration.” Biophysical J. 117(1): 170-183 (2019). Article.
 Ly C and Weinberg SH, “Analysis of heterogeneous cardiac pacemaker tissue models and traveling wave dynamics.” J. Theoretical Biology. 459:18-35 (2018). Article.
 Phadumdeo V and Weinberg SH, “Heart rate variability alters cardiac repolarization and electromechanical dynamics.” J. Theoretical Biology. 442:31-43 (2018). Article.
 Weinberg SH and Santamaria F, “History Dependent Neuronal Activity Modeled with Fractional Order Dynamics.” In: Computational Models of Brain and Behavior. Ahmed Moustafa, ed., Wiley-Blackwell. Chapter 39: 531-548 (2018). Book Chapter
 Lemmon CA and Weinberg SH, “Multiple cryptic binding sites are necessary for robust fibronectin assembly: an in silico study.” Scientific Reports. 7: 18061 (2017). Article
 Weinberg SH, “Ephaptic coupling rescues conduction failure in weakly coupled cardiac tissue with voltage-gated gap junctions.” Chaos. 27: 093908 (2017). Article
 Comlekoglu T and Weinberg SH, “Memory in a fractional-order cardiomyocyte model alters properties of alternans and spontaneous activity.” Chaos. 27: 093904 (2017). Article
 Weinberg SH, Mair DB, and Lemmon CA, “Mechanotransduction dynamics at the cell-matrix interface.” Biophysical J. 112: 1962-1974 (2017). Article featured as New and Notable; in VCU Engineering, VCU News, Phys.org
 Greer-Short A, George S, Poelzing S*, and Weinberg SH*, “Revealing the concealed nature of long QT type 3 syndrome.” Circulation: Arrhythm Electrophysiol. 10(2): e004400 (2017). Article featured with Editorial Commentary
 Ji H, Li Y, and Weinberg SH. “Calcium fluctuations alter ion channels gating in a stochastic representation of a luminal calcium release site model.” IEEE/ACM Transactions on Computational Biology and Bioinformatics. 14(3): 611-619 (2017). Article
 Deo M, Weinberg SH, and Boyle P, “Calcium Dynamics and Cardiac Arrhythmias.” Clinical Medicine Insights: Cardiology. 11: 1-4 (2017). Editorial
 Limbu B, Shah K, Weinberg SH, and Deo M, “Role of cytosolic calcium diffusion in murine cardiac Purkinje cells.” Clinical Medicine Insights: Cardiology. 10(S1): 17-26 (2016) Article
 Weinberg SH, “Impaired sarcoplasmic reticulum calcium uptake and release promote electromechanically and spatially discordant alternans: A computational study.” Clinical Medicine Insights: Cardiology. 10(S1): 1-15 (2016). Article
 Weinberg SH. “Microdomain calcium concentration fluctuations alter temporal dynamics in models of calcium-dependent signaling cascades and synaptic vesicle release.” Neural Computation. 28(3): 493-524 (2016). Article
 Wang X, Hardcastle K, Weinberg SH, and Smith GD. “Population density and moment-based approaches to modeling domain calcium-mediated inactivation of L-type calcium channels.” Acta Biotheoretica. 64: 11-32 (2016). Article
 Weinberg SH. “Spatial discordance and phase reversals during alternate pacing in discrete-time kinematic and cardiomyocyte ionic models.” Chaos. 25: 103119 (2015). Article
 Weinberg SH, “Membrane capacitive memory alters spiking in neurons described by the fractional-order Hodgkin-Huxley model.” PLoS ONE. 10(5): e0126629 (2015). Article
 Wang X, Hao Y, Weinberg SH, and Smith GD. “A theoretical study of Ca2+ spark statistics via a Langevin formulation of stochastic Ca2+ release via coupled intracellular channels.” Mathematical Biosciences. 264: 101-107 (2015). Article
 Wang X, Weinberg SH, Hao Y, Sobie EA, and Smith GD, “Calcium homeostasis in a local/global whole cell model of permeabilized ventricular myocytes with a Langevin description of stochastic calcium release.” Am J Physiol. Heart Circ Physiol. 308: H510-H523 (2015). Article
 Weinberg SH. “Personalized computational modeling for the treatment of cardiac arrhythmias,” In: The Digital Patient: Advancing Medical Research, Education, and Practice. D Combs, J Sokolowski, C Banks, eds., John Wiley & Sons, Inc., Chapter 8: 85-99 (2015). Chapter
2014 and earlier
 Weinberg SH, “High frequency stimulation of cardiac myocytes: A theoretical and computational study.” Chaos. 24: 043104 (2014). Article
 Weinberg SH and Smith GD, “Influence of Ca2+ buffers on free [Ca2+] fluctuations and the effective volume of Ca2+ microdomains.” Biophys. J. 106(12): 2693-2709 (2014). Article
 Weinberg SH, “High-frequency stimulation of excitable cells and networks.” PLoS ONE 8(11): e81402 (2013). Article
 Weinberg SH, Chang KC, Zhu R, Tandri H, Berger RD, Trayanova NA, and Tung L, “Defibrillation success by high frequency electric fields is related to degree and location of conduction block.” Heart Rhythm 10(5): 740-748. 2013. Article featured on the journal cover and with an Editorial Commentary
 Weinberg M, Weedn V, Weinberg S, and Fowler D. “Characteristics of medical examiner/coroners offices currently accredited by the National Association of Medical Examiners.” J. Forensic Sci. 58(5): 1193-1199 (2013). Article
 Blazeski A, Zhu R, Hunter DW, Weinberg SH, Zambidis ET, and Tung L. “Cardiomyocytes derived from human induced pluripotent stem cells as models for normal and diseased electrophysiology and contractility.” Prog. Biophys. Mol. Biol. 110(2-3): 166-77 (2012). Review
 Blazeski A, Zhu R, Hunter DW, Weinberg SH, Boheler KR, Zambidis ET, and Tung L. “Electrophysiological and contractile function of cardiomyocytes derived from human embryonic stem cells.” Prog. Biophys. Mol. Biol. 110(2-3): 178-95 (2012). Review
 Weinberg SH and Smith GD, “Discrete-state stochastic models of calcium-regulated calcium influx are often not well-approximated by continuous mass-action descriptions of subspace dynamics.” Comput. Math. Methods Med.: Special Issue on Cardiovascular System Modeling 2012: 897371 (2012). Article
 Weinberg SH and Tung L, “Oscillation in cycle length induces transient discordant and steady-state concordant alternans in the heart.” PLoS ONE 7(7): e40477 (2012). Article
 Tandri H*, Weinberg SH*, Chang KC, Zhu R, Trayanova NA, Tung L, and Berger RD, “Reversible cardiac conduction block and defibrillation with high-frequency electric field.” Science Transl. Med. 3: 102ra96 (2011). Article featured in NBC News, InsideScience, Duke Medicine Health News, The Atlantic, LiveScience
 Burridge PW, Thompson S, Millrod MA, Weinberg S, Yuan X, Peters A, Mahairaki V, Koliatsos V, Tung L, and Zambidis ET, “A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability.” PLoS ONE 6(4): e18293 (2011). Article featured in ScienceDaily
 Weinberg S, Lipke EA, and Tung L, “In vitro electrophysiological mapping of stem cells,” In: Stem Cells for Myocardial Regeneration: Methods and Protocols, Methods in Molecular Biology. RJ Lee, ed., Humana Press, 660: 215-37 (2010). Chapter
 Weinberg S, Malhotra N, and Tung L, “Vulnerable windows define susceptibility to alternans and spatial discordance.” Am J Physiol. Heart Circ Physiol. 298 (6): H1727-1737 (2010). Article
 Anderson WS, Kudela P, Weinberg S, Bergey GK, and Franaszczuk PJ, “Phase-dependent stimulation effects on bursting activity in a neural network cortical simulation.” Epilepsy Res. 84 (1): 42-55 (2009). Article
 Weinberg S, Iravanian S, and Tung L, “Representation of collective electrical behavior of cardiac cell sheets.” Biophys. J. 95: 1138-1150 (2008). Article
 Sarunic MV, Weinberg S, and Izatt JA, “Full-field swept-source phase microscopy,” Optics Letters 31: 1462-1464 (2006). Article
Justin Bui, REU Undergraduate Research, 2018
Tien Comlekoglu, Undergraduate Research - Currently MD student at University of Virginia
Ana Gonzalez, Undergraduate Research
Michelle Nguyen, Undergraduate Research
Navpreet Saini, MS, Biomedical Engineering, Virginia Commonealth University, 2019 - Currently PhD student at the University of Buffalo
Anderson Scott, Undergraduate Research
Lewis Scott, PhD, Biomedical Engineering, Virginia Commonwealth University, 2019 - Currently post-doctoral researcher at Genetech
Julia Smith, Undergraduate Research