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General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy.

Li Z, Mirams GR, Yoshinaga T, Ridder BJ, Han X, Chen JE, Stockbridge NL, Wisialowski TA, Damiano B, Severi S, Morissette P, Kowey PR, Holbrook M, Smith G, Rasmusson RL, Liu M, Song Z, Qu Z, Leishman DJ, Steidl-Nichols J, Rodriguez B, Bueno-Orovio A, Zhou X, Passini E, Edwards AG, Morotti S, Ni H, Grandi E, Clancy CE, Vandenberg J, Hill A, Nakamura M, Singer T, Polonchuk L, Greiter-Wilke A, Wang K, Nave S, Fullerton A, Sobie EA, Paci M, Musuamba Tshinanu F, Strauss DG.

Clin Pharmacol Ther. 2020 Jan;107(1):102-111. doi: 10.1002/cpt.1647. Epub 2019 Nov 10.


A stochastic model of ion channel cluster formation in the plasma membrane.

Sato D, Hernández-Hernández G, Matsumoto C, Tajada S, Moreno CM, Dixon RE, O'Dwyer S, Navedo MF, Trimmer JS, Clancy CE, Binder MD, Santana LF.

J Gen Physiol. 2019 Sep 2;151(9):1116-1134. doi: 10.1085/jgp.201912327. Epub 2019 Aug 1.


A computational model of induced pluripotent stem-cell derived cardiomyocytes incorporating experimental variability from multiple data sources.

Kernik DC, Morotti S, Wu H, Garg P, Duff HJ, Kurokawa J, Jalife J, Wu JC, Grandi E, Clancy CE.

J Physiol. 2019 Sep;597(17):4533-4564. doi: 10.1113/JP277724. Epub 2019 Jul 27.


A demonstration of modularity, reuse, reproducibility, portability and scalability for modeling and simulation of cardiac electrophysiology using Kepler Workflows.

Yang PC, Purawat S, Ieong PU, Jeng MT, DeMarco KR, Vorobyov I, McCulloch AD, Altintas I, Amaro RE, Clancy CE.

PLoS Comput Biol. 2019 Mar 8;15(3):e1006856. doi: 10.1371/journal.pcbi.1006856. eCollection 2019 Mar.


Structural basis for antiarrhythmic drug interactions with the human cardiac sodium channel.

Nguyen PT, DeMarco KR, Vorobyov I, Clancy CE, Yarov-Yarovoy V.

Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):2945-2954. doi: 10.1073/pnas.1817446116. Epub 2019 Feb 6.


Compartmentalized cAMP Signaling Associated With Lipid Raft and Non-raft Membrane Domains in Adult Ventricular Myocytes.

Agarwal SR, Gratwohl J, Cozad M, Yang PC, Clancy CE, Harvey RD.

Front Pharmacol. 2018 Apr 23;9:332. doi: 10.3389/fphar.2018.00332. eCollection 2018.


Determinants of Isoform-Specific Gating Kinetics of hERG1 Channel: Combined Experimental and Simulation Study.

Perissinotti LL, De Biase PM, Guo J, Yang PC, Lee MC, Clancy CE, Duff HJ, Noskov SY.

Front Physiol. 2018 Apr 12;9:207. doi: 10.3389/fphys.2018.00207. eCollection 2018.


Sex, drugs, and funky rhythms.

Vorobyov I, Clancy CE.

Heart Rhythm. 2018 Apr;15(4):485-486. doi: 10.1016/j.hrthm.2018.01.028. No abstract available.


Digging into Lipid Membrane Permeation for Cardiac Ion Channel Blocker d-Sotalol with All-Atom Simulations.

DeMarco KR, Bekker S, Clancy CE, Noskov SY, Vorobyov I.

Front Pharmacol. 2018 Feb 1;9:26. doi: 10.3389/fphar.2018.00026. eCollection 2018.


Dynamics of sodium current mediated early afterdepolarizations.

Sato D, Clancy CE, Bers DM.

Heliyon. 2017 Sep 6;3(9):e00388. doi: 10.1016/j.heliyon.2017.e00388. eCollection 2017 Sep.


A multiscale computational modelling approach predicts mechanisms of female sex risk in the setting of arousal-induced arrhythmias.

Yang PC, Perissinotti LL, López-Redondo F, Wang Y, DeMarco KR, Jeng MT, Vorobyov I, Harvey RD, Kurokawa J, Noskov SY, Clancy CE.

J Physiol. 2017 Jul 15;595(14):4695-4723. doi: 10.1113/JP273142. Epub 2017 Jun 14.


Potassium currents in the heart: functional roles in repolarization, arrhythmia and therapeutics.

Chiamvimonvat N, Chen-Izu Y, Clancy CE, Deschenes I, Dobrev D, Heijman J, Izu L, Qu Z, Ripplinger CM, Vandenberg JI, Weiss JN, Koren G, Banyasz T, Grandi E, Sanguinetti MC, Bers DM, Nerbonne JM.

J Physiol. 2017 Apr 1;595(7):2229-2252. doi: 10.1113/JP272883. Epub 2017 Jan 5. Review.


Reply from Pei-Chi Yang, Jonathan D. Moreno, Mao-Tsuen Jeng, Xander H. T. Wehrens, Sergei Noskov and Colleen E. Clancy.

Yang PC, Moreno JD, Jeng MT, Wehrens XH, Noskov S, Clancy CE.

J Physiol. 2016 Nov 1;594(21):6433-6435. doi: 10.1113/JP273143. No abstract available.


Sex hormonal regulation of cardiac ion channels in drug-induced QT syndromes.

Kurokawa J, Kodama M, Clancy CE, Furukawa T.

Pharmacol Ther. 2016 Dec;168:23-28. doi: 10.1016/j.pharmthera.2016.09.004. Epub 2016 Sep 4. Review.


Cardiac Na Channels: Structure to Function.

DeMarco KR, Clancy CE.

Curr Top Membr. 2016;78:287-311. doi: 10.1016/bs.ctm.2016.05.001. Epub 2016 Jun 14.


A computational model predicts adjunctive pharmacotherapy for cardiac safety via selective inhibition of the late cardiac Na current.

Yang PC, El-Bizri N, Romero L, Giles WR, Rajamani S, Belardinelli L, Clancy CE.

J Mol Cell Cardiol. 2016 Oct;99:151-161. doi: 10.1016/j.yjmcc.2016.08.011. Epub 2016 Aug 18.


A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation.

Yang PC, Boras BW, Jeng MT, Docken SS, Lewis TJ, McCulloch AD, Harvey RD, Clancy CE.

PLoS Comput Biol. 2016 Jul 13;12(7):e1005005. doi: 10.1371/journal.pcbi.1005005. eCollection 2016 Jul.


A novel heterozygous mutation in cardiac calsequestrin causes autosomal dominant catecholaminergic polymorphic ventricular tachycardia.

Gray B, Bagnall RD, Lam L, Ingles J, Turner C, Haan E, Davis A, Yang PC, Clancy CE, Sy RW, Semsarian C.

Heart Rhythm. 2016 Aug;13(8):1652-60. doi: 10.1016/j.hrthm.2016.05.004. Epub 2016 May 5.


Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention.

Zhang Y, Barocas VH, Berceli SA, Clancy CE, Eckmann DM, Garbey M, Kassab GS, Lochner DR, McCulloch AD, Tran-Son-Tay R, Trayanova NA.

Ann Biomed Eng. 2016 Sep;44(9):2642-60. doi: 10.1007/s10439-016-1628-0. Epub 2016 May 2.


Parameterization for In-Silico Modeling of Ion Channel Interactions with Drugs.

Moreno JD, Lewis TJ, Clancy CE.

PLoS One. 2016 Mar 10;11(3):e0150761. doi: 10.1371/journal.pone.0150761. eCollection 2016.


Multiscale Modeling in the Clinic: Drug Design and Development.

Clancy CE, An G, Cannon WR, Liu Y, May EE, Ortoleva P, Popel AS, Sluka JP, Su J, Vicini P, Zhou X, Eckmann DM.

Ann Biomed Eng. 2016 Sep;44(9):2591-610. doi: 10.1007/s10439-016-1563-0. Epub 2016 Feb 17. Review.


Mechanisms Restricting Diffusion of Intracellular cAMP.

Agarwal SR, Clancy CE, Harvey RD.

Sci Rep. 2016 Jan 22;6:19577. doi: 10.1038/srep19577.


In silico prediction of drug therapy in catecholaminergic polymorphic ventricular tachycardia.

Yang PC, Moreno JD, Miyake CY, Vaughn-Behrens SB, Jeng MT, Grandi E, Wehrens XH, Noskov SY, Clancy CE.

J Physiol. 2016 Feb 1;594(3):567-93. doi: 10.1113/JP271282. Epub 2015 Dec 30.


Mechanisms of Calmodulin Regulation of Different Isoforms of Kv7.4 K+ Channels.

Sihn CR, Kim HJ, Woltz RL, Yarov-Yarovoy V, Yang PC, Xu J, Clancy CE, Zhang XD, Chiamvimonvat N, Yamoah EN.

J Biol Chem. 2016 Jan 29;291(5):2499-509. doi: 10.1074/jbc.M115.668236. Epub 2015 Oct 29.


Kinetic model for NS1643 drug activation of WT and L529I variants of Kv11.1 (hERG1) potassium channel.

Perissinotti LL, Guo J, De Biase PM, Clancy CE, Duff HJ, Noskov SY.

Biophys J. 2015 Mar 24;108(6):1414-1424. doi: 10.1016/j.bpj.2014.12.056.


Na+/Ca2+ exchange and Na+/K+-ATPase in the heart.

Shattock MJ, Ottolia M, Bers DM, Blaustein MP, Boguslavskyi A, Bossuyt J, Bridge JH, Chen-Izu Y, Clancy CE, Edwards A, Goldhaber J, Kaplan J, Lingrel JB, Pavlovic D, Philipson K, Sipido KR, Xie ZJ.

J Physiol. 2015 Mar 15;593(6):1361-82. doi: 10.1113/jphysiol.2014.282319. Review.


Na+ channel function, regulation, structure, trafficking and sequestration.

Chen-Izu Y, Shaw RM, Pitt GS, Yarov-Yarovoy V, Sack JT, Abriel H, Aldrich RW, Belardinelli L, Cannell MB, Catterall WA, Chazin WJ, Chiamvimonvat N, Deschenes I, Grandi E, Hund TJ, Izu LT, Maier LS, Maltsev VA, Marionneau C, Mohler PJ, Rajamani S, Rasmusson RL, Sobie EA, Clancy CE, Bers DM.

J Physiol. 2015 Mar 15;593(6):1347-60. doi: 10.1113/jphysiol.2014.281428. Review.


Deranged sodium to sudden death.

Clancy CE, Chen-Izu Y, Bers DM, Belardinelli L, Boyden PA, Csernoch L, Despa S, Fermini B, Hool LC, Izu L, Kass RS, Lederer WJ, Louch WE, Maack C, Matiazzi A, Qu Z, Rajamani S, Rippinger CM, Sejersted OM, O'Rourke B, Weiss JN, Varró A, Zaza A.

J Physiol. 2015 Mar 15;593(6):1331-45. doi: 10.1113/jphysiol.2014.281204. Review. Erratum in: J Physiol. 2016 Mar 15;594(6):1791.


A computational modelling approach combined with cellular electrophysiology data provides insights into the therapeutic benefit of targeting the late Na+ current.

Yang PC, Song Y, Giles WR, Horvath B, Chen-Izu Y, Belardinelli L, Rajamani S, Clancy CE.

J Physiol. 2015 Mar 15;593(6):1429-42. doi: 10.1113/jphysiol.2014.279554.


Role of membrane microdomains in compartmentation of cAMP signaling.

Agarwal SR, Yang PC, Rice M, Singer CA, Nikolaev VO, Lohse MJ, Clancy CE, Harvey RD.

PLoS One. 2014 Apr 21;9(4):e95835. doi: 10.1371/journal.pone.0095835. eCollection 2014.


In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome.

Romero L, Trenor B, Yang PC, Saiz J, Clancy CE.

J Mol Cell Cardiol. 2014 Jul;72:126-37. doi: 10.1016/j.yjmcc.2014.02.018. Epub 2014 Mar 11. Corrected and republished in: J Mol Cell Cardiol. 2015 Oct;87:271-82.


Biological techniques: Wrapped around the heart.

Clancy CE, Xiang YK.

Nature. 2014 Mar 6;507(7490):43-4. doi: 10.1038/507043a. No abstract available.


Computational Models for Predictive Cardiac Ion Channel Pharmacology.

Yarov-Yarovoy V, Allen TW, Clancy CE.

Drug Discov Today Dis Models. 2014 Winter;14:3-10. Epub 2014 Aug 5.


Ranolazine for congenital and acquired late INa-linked arrhythmias: in silico pharmacological screening.

Moreno JD, Yang PC, Bankston JR, Grandi E, Bers DM, Kass RS, Clancy CE.

Circ Res. 2013 Sep 13;113(7):e50-e61. doi: 10.1161/CIRCRESAHA.113.301971. Epub 2013 Jul 29.


An LQTS6 MiRP1 mutation suppresses pacemaker current and is associated with sinus bradycardia.

Nawathe PA, Kryukova Y, Oren RV, Milanesi R, Clancy CE, Lu JT, Moss AJ, Difrancesco D, Robinson RB.

J Cardiovasc Electrophysiol. 2013 Sep;24(9):1021-7. doi: 10.1111/jce.12163. Epub 2013 Apr 30.


Cardiac electrophysiological dynamics from the cellular level to the organ level.

Sato D, Clancy CE.

Biomed Eng Comput Biol. 2013 Aug 26;5:69-75. doi: 10.4137/BECB.S10960. eCollection 2013. Review.


Computational modeling reveals dendritic origins of GABA(A)-mediated excitation in CA1 pyramidal neurons.

Lewin N, Aksay E, Clancy CE.

PLoS One. 2012;7(10):e47250. doi: 10.1371/journal.pone.0047250. Epub 2012 Oct 12. Erratum in: PLoS One. 2013;8(5). doi:10.1371/annotation/d6af29ee-25c0-4f8e-910e-afe53ef8f963.


In silico Prediction of Sex-Based Differences in Human Susceptibility to Cardiac Ventricular Tachyarrhythmias.

Yang PC, Clancy CE.

Front Physiol. 2012 Sep 14;3:360. doi: 10.3389/fphys.2012.00360. eCollection 2012.


Sex and gender aspects in antiarrhythmic therapy.

Kurokawa J, Kodama M, Furukawa T, Clancy CE.

Handb Exp Pharmacol. 2012;(214):237-63. doi: 10.1007/978-3-642-30726-3_12. Review.


Computational approaches to understand cardiac electrophysiology and arrhythmias.

Roberts BN, Yang PC, Behrens SB, Moreno JD, Clancy CE.

Am J Physiol Heart Circ Physiol. 2012 Oct 1;303(7):H766-83. doi: 10.1152/ajpheart.01081.2011. Epub 2012 Aug 10. Review.


Pathophysiology of the cardiac late Na current and its potential as a drug target.

Moreno JD, Clancy CE.

J Mol Cell Cardiol. 2012 Mar;52(3):608-19. doi: 10.1016/j.yjmcc.2011.12.003. Epub 2011 Dec 16. Review.


A computational model to predict the effects of class I anti-arrhythmic drugs on ventricular rhythms.

Moreno JD, Zhu ZI, Yang PC, Bankston JR, Jeng MT, Kang C, Wang L, Bayer JD, Christini DJ, Trayanova NA, Ripplinger CM, Kass RS, Clancy CE.

Sci Transl Med. 2011 Aug 31;3(98):98ra83. doi: 10.1126/scitranslmed.3002588.


Gender-based differences in cardiac diseases.

Yang PC, Clancy CE.

J Biomed Res. 2011 Mar;25(2):81-9. doi: 10.1016/S1674-8301(11)60010-9.


Determinants of heterogeneity, excitation and conduction in the sinoatrial node: a model study.

Oren RV, Clancy CE.

PLoS Comput Biol. 2010 Dec 23;6(12):e1001041. doi: 10.1371/journal.pcbi.1001041.


Arrhythmia models: in vivo, in vitro and in silico.

Akar FG, Clancy CE.

Drug Discov Today Dis Models. 2009 Fall;6(3):55-56. No abstract available.


Using computational modeling to predict arrhythmogenesis and antiarrhythmic therapy.

Moreno JD, Clancy CE.

Drug Discov Today Dis Models. 2009 Fall;6(3):71-84.


Effects of sex hormones on cardiac repolarization.

Yang PC, Clancy CE.

J Cardiovasc Pharmacol. 2010 Aug;56(2):123-9. doi: 10.1097/FJC.0b013e3181d6f7dd. Review.


Acute effects of sex steroid hormones on susceptibility to cardiac arrhythmias: a simulation study.

Yang PC, Kurokawa J, Furukawa T, Clancy CE.

PLoS Comput Biol. 2010 Jan 29;6(1):e1000658. doi: 10.1371/journal.pcbi.1000658.


Age-dependent changes in Na current magnitude and TTX-sensitivity in the canine sinoatrial node.

Protas L, Oren RV, Clancy CE, Robinson RB.

J Mol Cell Cardiol. 2010 Jan;48(1):172-80. doi: 10.1016/j.yjmcc.2009.07.028. Epub 2009 Aug 7.

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