Hund Lab for Excitable Cell Engineering
Hund Lab
Excitable Cell Engineering

Teaching
Dr. Hund teaches the following courses:
Numerical Simulations in Biomedical Engineering (BIOMEDE 2700) – A required course for Biomedical Engineering Undergraduate students, this course addresses application of computer-based numerical and graphical display skills for solving problems in biomedical engineering. Offered every Spring semester (Dr. Hund serves as primary instructor every other Spring).
Excitable Cell Engineering (BIOMEDE 5580) – A graduate level course (also open to senior level undergraduate students) that focuses on quantitative approaches to understanding excitable cell function. Offered every other Spring semester.
Research

Ca2+/calmodulin-dependent kinase II-dependent signaling in disease
Among the longest standing efforts of our group has been to understand the relationship between CaMKII dysregulation and cardiac disease. Specifically, we have developed and applied novel experimental and computational tools to determine the underlying molecular mechanism for CaMKII-dependent regulation of voltage-gated Na+ channel activity, cell membrane excitability, and heart function.
Representative publications
Glynn P, Musa H, Wu X, Unudurthi SD, Little S, Qian L, Wright PJ, Radwanski PB, Gyorke S, Mohler PJ, Hund TJ. Voltage-gated sodium channel phosphorylation at Ser571 regulates late current, arrhythmias, and cardiac function in vivo. Circulation. 2015; 132:567-577. PMCID: PMC4543581.
Koval OM, Snyder JS, Wolf RM, Pavlovicz RE, Glynn P, Curran J, Leymaster ND, Dun W, Wright PJ, Cardona N, Qian L, Mitchell CC, Boyden PA, Binkley PF, Li C, Anderson ME, Mohler PJ, and Hund TJ. Ca2+/calmodulin-dependent protein kinase II-based regulation of voltage-gated Na+ channel in cardiac disease. Circulation. 2012; 126:2084-2094. PMCID: PMC3811023.
Christensen MD, Dun W, Boyden PA, Anderson ME, Mohler PJ, and Hund TJ. Oxidized calmodulin kinase II regulates conduction following myocardial infarction: A computational analysis. PLoS Comput Biol. 2009; 5:e1000583. PMCID: PMC2778128.
Hund TJ, Decker KF, Kanter E, Mohler PJ, Boyden PA, Schuessler RB, Yamada KA, Y Rudy. Role of activated CaMKII in abnormal calcium homeostasis and INa remodeling after myocardial infarction: Insights from mathematical modeling. J Mol Cell Cardiol. 2008;45:420-8. PMCID: PMC2587155.

Spectrin-based pathways for regulation of cardiac excitability
Recent efforts from the Hund lab have focused on novel roles for the actin-associated protein βIV-spectrin in organizing ion channel macromolecular complexes in heart. While previous studies were restricted to brain, we have identified a critical role for βIV-spectrin in organizing specific ion channel regulatory complexes at the cardiomyocyte intercalated disc.
Representative publications
Hund TJ, Koval OM, Li J, Wright PJ, Qian L, Snyder JS, Gudmundsson H, Kline CF, Davidson NP, Cardona N, Rasband MN, Anderson ME, and Mohler PJ. A betaIV spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest. 2010; 120:3508-19. PMCID: PMC2947241.
Hund TJ, Snyder JS, Wu X, Glynn P, Koval OM, Onal B, Leymaster ND, Unudurthi SD, Curran J, Camardo C, Wright PJ, Binkley PF, Anderson ME, Mohler PJ. βIV-spectrin regulates TREK-1 membrane targeting in heart. Cardiovasc Res. 2014; 102:166-75. PMCID:PMC3958619.
Smith SA, Sturm AC, Curran J, Kline CF, Little SC, Bonilla IM, Long VP, Makara M, Polina I, Hughes LD, Webb TR, Wei Z, Wright P, Voigt N, Bhakta D, Spoonamore KG, Zhang C, Weiss R, Binkley PF, Janssen PM, Kilic A, Higgins RS, Sun M, Ma J, Dobrev D, Zhang M, Carnes CA, Vatta M, Rasband MN, Hund TJ, Mohler PJ. Dysfunction in the βII spectrin-dependent cytoskeleton underlies human arrhythmia. Circulation. 2015; 131:695-708. PMCID:PMC4342332
Unudurthi SD, Wu X, Qian L, Amari F, Onal B, Li N, Makara MA, Smith SA, Snyder J, Fedorov VV, Coppola V, Anderson ME, Mohler PJ, Hund TJ. Two-pore K+ channel TREK-1 regulates sinoatrial node membrane excitability. J Am Heart Assoc. 2016; 5:e002865. PMCID:PMC4859279.

Cardiac pacemaking mechanisms
The sinoatrial node is collection of specialized cells in the right atrium, responsible for controlling the normal heart rhythm. Sinoatrial node dysfunction, characterized by clinical signs of bradycardia, sinus pause or arrest, and supraventricular arrhythmia, is common in elderly but may be observed at any age due to a host of factors. The Hund lab has utilized an integrative approach to identify cell and tissue level factors important for synchronization of spontaneous sinoatrial node activity.
Representative publications
Luo M, Guan X, Di L, Kutschke W, Gao Z, Yang J, Luczak ED, Glynn P, Swaminathan PD, Weiss RM, Yang B, Rokita AG, Sossalla S, Maier LS, Efimov I, Hund TJ, Anderson ME. Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J Clin Invest. 2013; 123:1262-74. PMCID: PMC3673230.
Swaminathan PD, Purohit A, Soni S, Voigt N, Singh MV, Glukhov AV, Gao Z, He JB, Luczak ED, Joiner MA, Kutschke W, Yang J, Donahue JK, Weiss RM, Grumbach IM, Ogawa M, Chen PS, Efimov I, Dobrev D, Mohler PJ, Hund TJ, and Anderson ME. Oxidized CaMKII causes sinus node dysfunction. J Clin Invest. 2011; 121:3277-88. PMCID: PMC3223923. co-corresponding author.
Wolf RM, Glynn P, Hashemi S, Zarei K, Mitchell CC, Anderson ME, Mohler PJ, and Hund TJ. Atrial fibrillation and sinus node dysfunction in human ankyrin-B syndrome: A computational analysis. Am J Physiol Heart Circ Physiol. 2013; 304:H1253-66. PMCID: PMC3652094. corresponding author.
Glynn P, Onal B, Hund TJ. Cycle length restitution in sinoatrial node cells: A theory for understanding spontaneous action potential dynamics. PLoS ONE. 2014; 9:e89049. PMCID:PMC3923067.
Unudurthi SD, Wu X, Qian L, Amari F, Onal B, Li N, Makara MA, Smith SA, Snyder J, Fedorov VV, Coppola V, Anderson ME, Mohler PJ, Hund TJ. Two-pore K+ channel TREK-1 regulates sinoatrial node membrane excitability. J Am Heart Assoc. 2016; 5:e002865. PMCID:PMC4859279.

Mathematical modeling of cardiac excitation and arrhythmias
The Hund lab has expertise in the development of detailed mathematical models of cardiac cells and tissue to study the role of cell signaling networks in congenital and acquired forms of cardiac arrhythmia. We have developed physiological models of the cardiac action potential that incorporate critical cell signaling and targeting pathways. Computer simulations have identified an important role for abnormal cell signaling in ion channel changes and cardiac arrhythmia following myocardial infarction, as well as in several congenital arrhythmia syndromes (e.g. Timothy syndrome, ankyrin-B syndrome). The overall goal of this research is to identify ionic mechanisms responsible for ion channel dysfunction and cardiac arrhythmia.
Representative publications
Onal B, Gratz D and Hund TJ. Ca2+/calmodulin-dependent regulation of atrial myocyte late Na+ current, Ca2+ cycling and excitability: a mathematical modeling study. Am J Physiol Heart Circ Physiol. 2017;313:H1227-H1239.
Glynn P, Onal B, Hund TJ. Cycle length restitution in sinoatrial node cells: A theory for understanding spontaneous action potential dynamics. PLoS ONE. 2014; 9:e89049. PMCID:PMC3923067.
Wolf RM, Glynn P, Hashemi S, Zarei K, Mitchell CC, Anderson ME, Mohler PJ, and Hund TJ. Atrial fibrillation and sinus node dysfunction in human ankyrin-B syndrome: A computational analysis. Am J Physiol Heart Circ Physiol. 2013; 304:H1253-66. PMCID: PMC3652094.
Wolf RM, Mitchell CC, Christensen MD, Mohler PJ, and Hund TJ. Defining new insight into atypical arrhythmia: a computational model of ankyrin-B-syndrome. Am J Physiol Heart Circ Physiol. 2010; 299:H1505-H1514.
Christensen MD, Dun W, Boyden PA, Anderson ME, Mohler PJ, and Hund TJ. Oxidized calmodulin kinase II regulates conduction following myocardial infarction: A computational analysis. PLoS Comput Biol. 2009; 5:e1000583. PMCID: PMC2778128.
Hund TJ, Decker KF, Kanter E, Mohler PJ, Boyden PA, Schuessler RB, Yamada KA, Y Rudy. Role of activated CaMKII in abnormal calcium homeostasis and INa remodeling after myocardial infarction: Insights from mathematical modeling. J Mol Cell Cardiol. 2008;45:420-8. PMCID: PMC2587155.
Hund TJ and Y Rudy. Rate dependence and regulation of the action potential and calcium transient in a canine cardiac ventricular cell model. Circulation. 2004; 110:3168-3174
LongQt is a graphical modeling application for heart cells. It provides a simple interface for choosing the type of cell model; adjusting simulation parameters; and viewing simulation results. See accompanying publication for more information:
Onal B, Gratz D, Hund T. LongQt:A cardiac electrophysiology simulation platform. MethodsX. 2016;3:589-599.
Current (version 0.4)
Source
Analysis Tools
Automated Fibrosis Analysis Tool (AFAT)
AFAT facilitates analysis of Masson’s trichrome stained heart sections for the relative amount of collagen in a repeatable, fast, and accurate manner with an easy-to-operate interface. No programming experience is needed to use the program in its current state. Configuration is possible to adjust for image variability/ staining quality, and the code may be easily tailored to suit a different imaging. Briefly, AFAT preforms the following steps to quantify fibrosis as a percentage of the tissue area:
- Convert image from RGB to HSV (Hue, Value, Saturation) and CIELAB color space, which was defined by the International Commission on Illumination (CIE) to allow for small numerical changes to equate to small differences in perceived color (perceptual uniformity);
- Filter image into following groups of pixels: white, red, blue, and pixels that do not readily fit into one of the other groups (undetermined);
- Apply linear regression to identify white pixels from undetermined pixels;
- Use K-Nearest Neighbors to classify the remaining undetermined points as red, blue, or still undetermined;
- Calculate the percent fibrosis as a fraction of blue and red pixels.
Macrophage Analysis Tool (MAT)
MAT facilitates rapid quantification of macrophage populations using immunostained heart sections. The program takes the image(s) to be processed, guides the user through a simple calibration procedure to ensure data accuracy, and provides enumeration of macrophages including size and location. The output dataset including the calibration information can be saved for reopening as well as exported to an Excel worksheet for further analysis.
Related News
Funding


Hund Lab for Excitable Cell Engineering
Davis Heart & Lung Research Institute
333 W. 10th Ave.
Columbus, OH 43210
Thomas.Hund@osumc.edu
Alex Winkle defends his MS thesis
Drew Nassal's new paper out in Journal of Biological Chemistry
Daniel Gratz and Alex Winkle publish new mathematical model in Cells
Jane Yu awarded BME Undergraduate Research Award
Connor Neifert and Jane Yu defend their Honors Research Theses
Cemantha Lane awarded an AHA predoctoral fellowship and 1st place at the OSU Hayes Forum!
Hund lab awarded new NIH grant to study TREK-1 channels and cardiac arrhythmia
Cemantha and Amara publish findings on sodium channels, obesity and atrial fibrillation!
Publications
Dewal R, Greer-Short A, Lane C, Nirengi S, Manzano PA, Hernandez-Saavedra D, Wright K, Nassal D, Baer L, Mohler PJ, Hund TJ, Stanford KI. Phospho-ablation of cardiac sodium channel Nav1.5 mitigates susceptibiliity to atrial fibrillation and improves glucose homeostasis under conditions of diet-induced obesity. Int J Obes (Lond). 2021;45:795-807.
Unudurthi SD, Nassal DM, Patel NJ, Thomas E, Yu J, Pierson CG, Bansal SS, Mohler PJ, Hund TJ. Fibroblast growth factor-inducible 14 mediates macrophage infiltration in heart to promote pressure overload-induced cardiac dysfunction. Life Sci. 2020;247:117440.
Greer-Short A, Musa H, Alsina KM, Ni L, Word TA, Reynolds JO, Gratz D, Lane C, El Refaey M, Unudurthi S, Skaf M, Li N, Fedorov VV, Wehrens XHT, Mohler PJ, Hund TJ. Calmodulin kinase II regulates atrial myocyte late sodium current, calcium handling and atrial arrhythmia. Heart Rhythm. 2020;17:503-11.
Patel NJ, Nassal DN, Greer-Short AD, Unudurthi SD, Scandling BW, Gratz D, Xu X, Kalyanasundaram A, Fedorov VV, Accornero F, Mohler PJ, Gooch KJ, Hund TJ. BetaIV-spectrin/STAT3 complex regulates fibroblast phenotype, fibrosis and cardiac function. JCI Insight. 2019;4:e131046.
Unudurthi SD, Nassal D, Greer-Short A, Patel N, Howard T, Xu X, Onal B, Satroplus T, Hong D, Lane C, Dalic A, Loenig SN, Lehnig AD, Baer LA, Musa H, Stanford KI, Smith S, Mohler PJ, Hund TJ. betaIV-spectrin regulates STAT3 targeting to tune cardiac response to pressure overload. J Clin Invest. 2018;128:5561-5572.
Howard T, Greer-Short A, Satroplus T, Patel N, Nassal D, Mohler PJ, Hund TJ. CaMKII-dependent late Na+ current increases electrical dispersion and arrhythmia in ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2018;315:H794-H801.
Gratz D, Onal B, Dalic A, Hund T. Synchronization of pacemaking in the sinoatrial node: a mathematical modeling study. Front Phys. 2018;6:63.
Onal B, Gratz D, Hund TJ. Ca2+/calmodulin-dependent regulation of atrial myocyte late Na+ current, Ca2+ cycling and excitability: a mathematical modeling study. Am J Physiol Heart Circ Physiol. 2017;313:H1227-H1239.
Onal B, Gratz D, Hund T. LongQt: A cardiac electrophysiology simulation platform. MethodsX. 2016; 3:589-599.
Unudurthi SD, Wu X, Qian L, Amari F, Onal B, Li N, Makara MA, Smith SA, Snyder J, Fedorov VV, Coppola V, Anderson ME, Mohler PJ, Hund TJ. The two-pore K+ channel TREK-1 regulates sinoatrial node membrane excitability. J Am Heart Assoc. 2016; 5:e002865.
Glynn P, Musa H, Wu X, Unudurthi SD, Little S, Qian L, Wright PJ, Radwanski PB, Gyorke S, Mohler PJ, Hund TJ. Voltage-gated sodium channel phosphorylation at Ser571 regulates late current, arrhythmia, and cardiac function in vivo. Circulation. 2015;132:567-577.
Hund TJ, Snyder JS, Wu X, Glynn P, Koval OM, Onal B, Leymaster ND, Unudurthi SD, Curran J, Camardo C, Wright PJ, Binkley PF, Anderson ME, Mohler PJ. BetaIV-spectrin regulates TREK-1 membrane targeting in heart. Cardiovasc Res. 2014; 102:166-75.
Glynn P, Onal B, Hund TJ. Cycle length restitution in sinoatrial node cells: A theory for understanding spontaneous action potential dynamics. PLoS ONE. 2014; 9:e89049.
Onal B, Unudurthi SD, Hund TJ. Modeling CaMKII in cardiac physiology: From molecule to tissue. Front Pharmacol. 2014; 5:9.
Unudurthi SD, Wolf RM, Hund TJ. Role of sinoatrial node architecture in maintaining a balanced source-sink relationship and synchronous cardiac pacemaking. Front Physiol. 2014; 5:446.
Wolf RM, Glynn P, Hashemi S, Zarei K, Mitchell CC, Anderson ME, Mohler PJ, Hund TJ. Atrial fibrillation and sinus node dysfunction in human ankyrin-B syndrome: A computational analysis. Am J Physiol Heart and Circ Physiol. 2013; 304:H1253-66.
Luo M, Guan X, Di L, Kutschke W, Gao Z, Yang J, Luczak ED, Glynn P, Swaminathan PD, Weiss RM, Yang B, Rokita AG, Sossalla S, Maier LS, Efimov I, Hund TJ, Anderson ME. Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J Clin Invest. 2013; 123:1262-74.
Koval OM, Snyder JS, Wolf RM, Pavlovicz RE, Glynn P, Curran J, Leymaster ND, Dun W, Wright PJ, Cardona N, Qian L, Mitchell CC, Boyden PA, Binkley PF, Li C, Anderson ME, Mohler PJ, and Hund TJ. Ca2+/calmodulin-dependent protein kinase II-based regulation of voltage-gated Na+ channel in cardiac disease. Circulation. 2012; 126:2084-2094.
Swaminathan PD, Purohit AS, Hund TJ, and Anderson ME. CaM Kinases: Linking heart failure and arrhythmias. Circ Res. 2012;110:1661-1677.
Swaminathan PD, Purohit A, Soni S, Voigt N, Singh MV, Glukhov AV, Gao Z, He JB, Luczak ED, Joiner MA, Kutschke W, Yang J, Donahue JK, Weiss RM, Grumbach IM, Ogawa M, Chen PS, Efimov I, Dobrev D, Mohler PJ, Hund TJ, and Anderson ME. Oxidized CaMKII causes cardiac sinus node dysfunction. J Clin Invest. 2011; 121:3277-88.
Hund TJ, Koval OM, Li J, Wright PJ, Qian L, Snyder JS, Gudmundsson H, Kline CF, Davidson NP, Cardona N, Rasband MN, Anderson ME, and Mohler PJ. A betaIV spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest. 2010;120:3508-19.
Wolf RM, Mitchell CC, Christensen MD, Mohler PJ, and Hund TJ. Defining new insight into atypical arrhythmia: a computational model of ankyrin-B-syndrome. Am J Physiol Heart Circ Physiol. 2010; 299:H1505-H1514.
Christensen MD, Dun W, Boyden PA, Anderson ME, Mohler PJ, and Hund TJ. Oxidized calmodulin kinase II regulates conduction following myocardial infarction: A computational analysis. PLoS Comput Biol. 2009; 5:e1000583.
Hund TJ, Wright P, Dun W, Snyder JS, Boyden PA, and Mohler PJ. Regulation of ankyrin-B-based targeting pathway following myocardial infarction. Cardiovasc Res. 2009; 81:742-749.
Hund TJ, Decker KF, Kanter E, Mohler PJ, Boyden PA, Schuessler RB, Yamada KA, and Y Rudy. Role of activated CaMKII in abnormal calcium homeostasis and INa remodeling after myocardial infarction: Insights from mathematical modeling. J Mol Cell Cardiol. 2008; 45:420-8.
Hund TJ and Y Rudy. Rate dependence and regulation of the action potential and calcium transient in a canine cardiac ventricular cell model. Circulation. 2004; 110:3168-3174.