Publications

1. K.T. Hellgren, H. Ni, S. Morotti,@ E. Grandi.@ Predictive male-to-female translation of cardiac electrophysiological response to drugs. JACC Clin Electrophysiol. 2023 Dec; 9(12):2642-2648 . DOI: 10.1016/j.jacep.2023.08.016  Highlighted by editorial

2. N.T. Herrera, X. Zhang, H. Ni, M.M. Maleckar. J. Heijman, D. Dobrev, E. Grandi,@ S. Morotti.@ Dual effects of the small-conductance Ca2+-activated K+ current on human atrial electrophysiology and Ca2+-driven arrhythmogenesis: an in silico study. Am J Physiol Heart Circ Physiol. 2023 Oct 1; 325(4):H896-H908. DOI: 10.1152/ajpheart.00362.2023 

3. H. Ni, S. Morotti, X. Zhang, D. Dobrev, E. Grandi.@ Integrative human atrial modeling unravels interactive PKA and CaMKII signaling as key determinant of atrial arrhythmogenesis. Cardiovasc Res. 2023 Oct 24; 119(13):2294-2311. DOI: 10.1093/cvr/cvad118  Editor’s choice

4. J.M. Hernandez, C.Y. Ko, A.R. Mandel, E.Y. Shen, S. Baidar, A.R. Christensen, K. Hellgren, S. Morotti, J.L. Martin, B. Hegyi, J. Bossuyt,@ D.M. Bers.@ Cardiac protein kinase D1 ablation alters the myocytes β-adrenergic response. J Mol Cell Cardiol. 2023 May 4;180:33-43. DOI: 10.1016/j.yjmcc.2023.05.001 

5. J. Heijman,* X. Zhou,* S. Morotti, C.E. Molina, I.H. Abu-Taha, M. Tekook, T. Jespersen, Y. Zhang, S. Dobrev, H. Milting, J. Gummert, M. Karck, M. Kamler, A. El-Armouche, A. Saljic, E. Grandi, S. Nattel, D. Dobrev.@ Enhanced SK-channel Ca2+ sensitivity and membrane trafficking in human atrial fibrillation. Circ Res. 2023 Apr 28;132(9):e116-e133. DOI: 10.1161/CIRCRESAHA.122.321858  Highlighted by editorial

6. Y. Ding, D. Lang, J. Yan, H. Bu, H. Li, K. Jiao, J. Yang, H. Ni, S. Morotti, T. Le, K.J. Clark, J. Port, S.C. Ekker, H. Cao, Y. Zhang, J. Wang, E. Grandi, Z. Li, Y. Shi, Y. Li, A.V. Glukhov, X. Xu.@ A phenotype-based forward genetic screen identifies Dnajb6 as a sick sinus syndrome gene. eLife. 2022 Oct 18;11:e77327. DOI: 10.7554/eLife.77327 

7. C.H. Peters,* C. Rickert,* S. Morotti, E. Grandi, K.A. Aronov, K.G. Beam, C. Proenza.@ The funny current If is essential for the fight-or-flight response in cardiac pacemaker cells. J Gen Physiol. 2022 Dec 5;154(12):e202213193. DOI: 10.1085/jgp.202213193 

8. X. Zhang, C.E.R. Smith, S. Morotti, A.G. Edwards, D. Sato, W.E. Louch, H. Ni, E. Grandi.@ Mechanisms of spontaneous Ca2+ release-mediated arrhythmia in a novel 3D human atrial myocyte model: II. Ca2+-handling protein variation. J Physiol. 2023 Jul; 601(13): 2685-2710. DOI: 10.1113/JP283602  Highlighted by editorial

9. X. Zhang, H. Ni, S. Morotti, C.E.R. Smith, D. Sato, W.E. Louch, A.G. Edwards, E. Grandi.@ Mechanisms of spontaneous Ca2+ release-mediated arrhythmia in a novel 3D human atrial myocyte model: I. Transverse-axial tubule variation. J Physiol. 2023 Jul; 601(13): 2655-2683. DOI: 10.1113/JP283363  Highlighted by editorial

10. S. Morotti,@ C. Liu, B. Hegyi, H. Ni, A. Fogli Iseppe, L. Wang, M. Pritoni, C.M. Ripplinger, D.M. Bers, A.G. Edwards, E. Grandi.@ Quantitative cross-species translators of cardiac myocyte electrophysiology: model training, experimental validation, and applications. Sci Adv. 2021 Nov 19; 7(47):eabg0927. DOI: 10.1126/sciadv.abg0927  Recommended by H1 Connect

11. S. Morotti,@ H. Ni, C.H. Peters, C. Rickert, A. Asgari-Targhi, D. Sato, A.V. Glukhov, C. Proenza, E. Grandi.@ Intracellular Na+ modulates pacemaking activity in murine sinoatrial node myocytes: an in silico analysis. Int J Mol Sci. 2021 May 26; 22(11):5645. DOI: 10.3390/ijms22115645 

12. C.H. Peters, P.W. Liu, S. Morotti, S. Gantz, E. Grandi, B.P. Bean, C. Proenza.@ Bi-direction flow of the funny current (If) during the cardiac cycle in murine sinoatrial myocytes. Proc Natl Acad Sci USA. 2021 Jul 13; 118(28):e2104668118. DOI: 10.1073/pnas.2104668118 

13. A. Fogli Iseppe, H. Ni, Z. Zhu. X. Zhang, R. Coppini, P-C. Yang, U. Srivatsa, C.E. Clancy, A.G. Edwards, S. Morotti, E. Grandi.@ Sex-specific classification of drug-induced Torsade de Pointes susceptibility using cardiac simulations and machine learning. Clin Pharmacol Ther. 2021 Aug; 110(2):380-391. DOI: 10.1002/cpt.2240 

14. S. Ljubojevic-Holzer, A.W. Herren, N. Djalinac, J. Voglhuber, S. Morotti, M. Holzer, B.M. Wood, I. Matzer, M. Sacherer, S. Radulovic, M. Abdellatif, M. Wallner, M. Ivanov, S. Wagner, S. Sossalla, D. Von Levinski, B. Pieske, J.H. Brown, S. Sedej, J. Bossuyt, D.M. Bers.@ CaMKIIδC drives early adaptive Ca2+ change and late eccentric cardiac hypertrophy. Circ Res. 2020 Oct 9; 127(9):1159-1178. DOI: 10.1161/CIRCRESAHA.120.316947  Editor’s pick

15. H. Ni, A. Fogli Iseppe, W. Giles, S.M. Narayan, H. Zhang, A.G. Edwards, S. Morotti, E. Grandi.@ Populations of in silico myocyte and tissues reveal synergy of multi-atrial-predominant K+ current block in atrial fibrillation. Br J Pharmacol. 2020 Jul 15; 177:4497-4515. DOI: 10.1111/bph.15198 

16. B. Xu, M. Li, Y. Wang, M. Zhao, S. Morotti, Q. Shi, Q. Wang, F. Barbagallo, J.P. Teoh, G.R. Reddy, E. Bayne, Y. Liu, A. Shen, J.L. Puglisi, Y. Ge, J. Li, E. Grandi, M. Nieves-Cintrón, Y.K. Xiang.@ GRK5 controls SAP97-dependent cardiotoxic β1 adrenergic receptor-CaMKII signaling in heart failure. Circ Res. 2020 Aug 28; 127(6):796-810. DOI: 10.1161/CIRCRESAHA.119.316319 

17. K. Tazmini,* M. Frisk,* A. Lewalle, M. Laasmaa, S. Morotti, D.B. Lipsett, O. Manfra, J. Skogested, J.M. Aronsen, O.M. Sejersted, I. Sjaastad, A.G. Edwards, E. Grandi, S.A. Niederer, E. Øie, W.E. Louch.@ Hypokalemia promotes arrhythmia by distinct mechanisms in atrial and ventricular myocytes. Circ Res. 2020 Mar 27; 126(7):889-906. DOI: 10.1161/CIRCRESAHA.119.315641 

18. Z. Li,@ G.R. Mirams, T. Yoshinaga, B.J. Ridder, X. Han, J.E. Chen, N.L. Stockbridge, T.A. Wisialowski, B. Damiano, S. Severi, P. Morissette, P.R. Kowey, M. Holbrook, G. Smith, R.L. Rasmusson, M. Liu, Z. Song, Z. Qu, D.J. Leishman, J. Steidl-Nichols, B. Rodriguez, A. Bueno-Orovio, X. Zhou, E. Passini, A.G. Edwards, S. Morotti, H. Ni, E. Grandi, C.E. Clancy, J. Vandenberg, A. Hill, M. Nakamura, T. Singer, L. Polonchuk, A. Greiter-Wilke, K. Wang, S. Nave, A. Fullerton, E.A. Sobie, M. Paci, F.M. Tshinanu, D.G. Strauss. General principles for the validation of proarrhythmia risk prediction models: an extension of the CiPA in silico strategy. Clin Pharmacol Ther. 2020 Jan; 107(1):102-111. DOI: 10.1002/cpt.1647  Top 10% most downloaded articles in the 12 months after publication

19. D.C. Kernik, S. Morotti, H. Wu, P. Garg, H.J. Duff, J. Kurokawa, J. Jalife, J.C. Wu, E. Grandi,@ C.E. Clancy.@ A computational model of induced pluripotent stem-cell derived cardiomyocytes incorporating experimental variability from multiple data sources. J Physiol. 2019 Sep; 597(17): 4533-4564. DOI: 10.1113/JP277724  Highlighted in a Journal Club article, top 10% most downloaded articles in the 12 months after publication, and selected for the “Experimental Biology” Virtual Issue 2020

20. L. Wang, S. Morotti, S. Tapa, S.D. Francis Stuart, Y. Jiang, Z. Wang, R.C. Myles, K.E. Brack, G.A. Ng, D.M. Bers, E. Grandi, C.M. Ripplinger.@ Different paths, same destination: Divergent electrophysiological responses result in conserved cardiac fight-or-flight response in mouse and rabbit hearts. J Physiol. 2019 Aug; 597(15):3867-3883. DOI: 10.1113/JP278016 

21. A.U. Syed,* G.R. Reddy,* D. Ghosh,* M.P. Prada, M.A. Nystoriak, S. Morotti, E. Grandi, P. Sirish, N. Chiamvimonvat, J.W. Hell, L.F. Santana, Y.K. Xiang, M. Nieves-Cintrón,@ M.F. Navedo.@ Adenylyl cyclase 5­-generated cAMP controls cerebral vascular reactivity during diabetic hyperglycemia. J Clin Invest. 2019 Jun 4; 129(8):3140-3152. DOI: 10.1172/JCI124705  Recommended by H1 Connect

22. B. Hegyi, S. Morotti, C. Liu, T. Bányász, K.S. Ginsburg, J. Bossuyt, L. Belardinelli, L.T. Izu, Y. Chen-Izu, E. Grandi, D.M. Bers.@ Enhanced depolarization drive in failing rabbit ventricular myocytes: calcium-dependent and β‑adrenergic effects on late sodium, L-type calcium and sodium-calcium exchange currents. Circ Arrhythm Electrophysiol. 2019 Mar; 12(3):e007061. DOI: 10.1161/CIRCEP.118.007061 

23. H. Ni, S. Morotti, E. Grandi.@ A heart for diversity: simulating variability in cardiac arrhythmia research. Front Physiol. 2018 Jul 20; 9:958. DOI: 10.3389/fphys.2018.00958 

24. S. Morotti, E. Grandi.@ Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the Na+-Ca2+-Ca2+/calmodulin-dependent protein kinase II-reactive oxygen species feedback. Wiley Interdiscip Rev Syst Biol Med. 2019 Mar; 11(2):e1434. DOI: 10.1002/wsbm.1434 

25. E. Grandi,@ S. Morotti, E. Pueyo, B. Rodriguez. Editorial: Safety pharmacology – Risk assessment QT interval prolongation and beyond. Front Physiol. 2018 Jun 8; 9:678. DOI: 10.3389/fphys.2018.00678 

26. R. Vaidyanathan, H. Van Ert, K. Haq, S. Morotti, E. McCune, S. Esch, J. Warden, S. Abozeid, E. Grandi, L. Eckhardt.@ Domain specific interaction of Caveolin-3 and inward rectifier potassium channels (Kir2.x): Implications for Purkinje cell dependent ventricular arrhythmias. Circ Arrhythm Electrophysiol. 2018 Jan; 11:e005800. DOI: 10.1161/CIRCEP.117.005800 

27. N. Ellinwood, D. Dobrev, S. Morotti,@ E. Grandi. In silico assessment of efficacy and safety of IKur inhibitors in chronic atrial fibrillation: role of kinetics and state-dependence of drug binding. Front Pharmacol. 2017 Nov 7; 8:799. DOI: 10.3389/fphar.2017.00799 

28. N. Ellinwood, D. Dobrev, S. Morotti, E. Grandi.@ Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity. Chaos. 2017 Sept; 27(9): 093918. DOI: 10.1063/1.5000226 

29. N.C. Surdo, M. Berrera, A. Koschinski, M. Brescia, M.R. Machado, C. Carr, P. Wright, J. Gorelik, S. Morotti, E. Grandi, D.M. Bers, S. Pantano, M. Zaccolo.@ FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility. Nat Commun. 2017 Apr 20; 8:15031. DOI: 10.1038/ncomms15031 

30. S. Morotti, M. Nieves-Cintrón, M.A. Nystoriak, M.F. Navedo,@ E. Grandi.@ Predominant contribution of L-type CaV1.2 channel stimulation to impaired intracellular calcium and cerebral artery vasoconstriction in diabetic hyperglycemia. Channels (Austin). 2017 Jul 4; 11(4):340-346. DOI: 10.1080/19336950.2017.1293220 

31. M.A. Nystoriak, M. Nieves-Cintrón, T. Patriarchi, O.R. Buonarati, M.P. Prada, S. Morotti, E. Grandi, J. Dos Santos Fernandes, K. Forbush, F. Hofmann, K.C. Sasse, J.D. Scott, S.M. Ward, J.W. Hell, M.F. Navedo.@ CaV1.2 Ser1928 phosphorylation by PKA stimulates L-type Ca2+ channels and vasoconstriction during acute hyperglycemia and diabetes. Sci Signal. 2017 Jan 24; 10:463. DOI: 10.1126/scisignal.aaf9647  Highlighted by journal cover and podcast  Recommended by H1 Connect

32. S. Morotti, E. Grandi.@ Logistic regression analysis of populations of electrophysiological models to assess proarrythmic risk. MethodsX. 2016 Dec 23; 4:25-34. DOI: 10.1016/j.mex.2016.12.002 

33. D.C. Bartos, S. Morotti, K.S. Ginsburg, E. Grandi, D.M. Bers.@ Quantitative analysis of the Ca2+-dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes. J Physiol. 2017 Apr 1; 595(Pt 7):2253-2268. DOI: 10.1113/JP273676  Highlighted by editorial, and selected for the “Biophysics” Virtual Issue 2018

34. S. Morotti, A.D. McCulloch, D.M. Bers, A.G. Edwards, E. Grandi.@ Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes. J Mol Cell Cardiol. 2016 Jul; 96:63-71. DOI: 10.1016/j.yjmcc.2015.07.030 

35. J.A. Negroni,@ S. Morotti, E.C. Lascano, A.V. Gomes, E. Grandi, J.L. Puglisi, D.M. Bers.@ β-adrenergic effects on cardiac myofilaments and contraction in an integrated rabbit ventricular myocyte model. J Mol Cell Cardiol. 2015 Apr; 81:162-75. DOI: 10.1016/j.yjmcc.2015.02.014 

36. D.M. Bers,@ S. Morotti. Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences. Front Pharmacol. 2014 Jun 17; 5:144. DOI: 10.3389/fphar.2014.00144 

37. S. Morotti, A.G. Edwards, A.D. McCulloch, D.M. Bers, E. Grandi.@ A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII. J Physiol. 2014 Mar 15; 592(Pt 6):1181-97. DOI: 10.1113/jphysiol.2013.266676  Selected for the “Editor’s Choice – New Papers in Cardiovascular Physiology” Virtual Issue 2014, and the “Biophysics and Innovation” Virtual Issue 2015

38. S. Morotti,* E. Grandi,* A. Summa, K.S. Ginsburg, D.M. Bers.@ Theoretical study of L-type Ca2+ current inactivation kinetics during action potential repolarization and early afterdepolarizations. J Physiol. 2012 Sep 15; 590(Pt 18):4465-81. DOI: 10.1113/jphysiol.2012.231886  Selected for the “Biophysics and Discovery” Virtual Issue 2013

39. Y. Ruan, M. Denegri, N. Liu, T. Bachetti, M. Seregni, S. Morotti, S. Severi, C. Napolitano, S.G. Priori.@ Trafficking defects and gating abnormalities of a novel SCN5A mutation question gene-specific therapy in Long QT Syndrome type 3. Circ Res. 2010 Apr 30; 106(8):1374-83. DOI: 10.1161/CIRCRESAHA.110.218891  Recommended by H1 Connect

40. E. Grandi, S. Morotti, K.S. Ginsburg, S. Severi, D.M. Bers.@ Interplay of voltage and Ca-dependent inactivation of L-type Ca current. Prog Biophys Mol Biol. 2010 Sep; 103(1):44-50. DOI: 10.1016/j.pbiomolbio.2010.02.001 

* equal contribution

@ corresponding author(s)