Eleonora Grandi

Eleonora Grandi

Position Title
Associate Professor

  • Department of Pharmacology, School of Medicine
Tupper Hall 2427

Profile Introduction

Mathematical modeling of cardiac myocyte electrophysiology, ion transport, and signaling in health and disease.

Research Interests

My research aims at understanding the cellular mechanisms of complex cardiac arrhythmia diseases, such as heart failure and atrial fibrillation. This is achieved by developing mechanistic computational models, based on bioengineering principles. The purpose of my studies is to develop frameworks for accurate prediction of disease mechanisms, which is expected to lend insight into the origins of clinical observations and aid the identification of pro-arrhythmic targets. These models also serve as platforms for testing of pharmacological interventions to guide therapeutic strategies.

Grad Group Affiliations

  • Molecular, Cellular and Integrative Physiology
  • Biomedical Engineering
  • Pharmacology and Toxicology
  • Biophysics

Specialties / Focus

  • Cardiorespiratory Physiology
  • Cellular and Molecular Physiology
  • Computational Physiology


  • 2003 MS Electronics Engineering University of Bologna
  • 2007 PhD Bioengineering University of Bologna


Complete List of Publications

  • Z. Li, G. Mirams, T. Yoshinaga, B. Ridder, X. Han, J. Chen, N. Stockbridge, T. Wisialowski, B. Damiano, S. Severi, P. Morissette, P. Kowey, M. Holbrook, G. Smith, R. Rusmusson, M. Liu, Z. Song, Z. Qu, D. Leishman, J. Steidl-Nichols, B. Rodriguez, A. Bueno-Orovio, X. Zhou, E. Passini, A. Edwards, S. Morotti, H. Ni, E. Grandi, C. Clancy, J. Vandenberg, A. Hill, M. Nakamura, T. Singer, L. Polonchuk, A. Greiter-Wilke, K. Wang, S. Nave, A. Fullerton, E. Sobie, M. Paci, F. Musuamba Tshinanu, D. Strauss. General Principles for the Validation of Proarrhythmia Risk Prediction Models: an Extension of the CiPA In Silico Strategy. Clin Pharmacol Ther, in press
  • D.C. Kernik, S. Morotti, H.J. Duff, J. Kurokawa, J. Jalife, J.C. Wu, E. Grandi, C.E. Clancy. A Computational Analysis of Inter-subject Variability in Induced Pluripotent Stem Cell-Derived Cardiomyocytes. J Physiol, 2019 Sep;597(17):4533-4564. 
  • L. Wang, S. Morotti, S. Tapa, S.D. Francis Stuart, Y. Jiang, R.C. Myles, 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. 
  • E. Grandi@ and C.M. Ripplinger. Antiarrhythmic mechanisms of beta blocker therapy. Pharmacol Res. 2019 Aug;146:104274. Review.
  • 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 and M.F. Navedo. AC5-generated cAMP controls cerebral vascular reactivity during diabetic hyperglycemia. J Clin Invest. 2019 Jun 4;129(8):3140-3152. 
  • 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. 
  • E. Grandi, D. Dobrev, J. Heijman. Computational modeling: what does it tell us about atrial fibrillation mechanisms and therapy? International Journal of Cardiology. Int J Cardiol. 2019 Jul 15;287:155-161. 
  • H. Ni, H. Zhang, E. Grandi, S. Narayan, W. Giles. Transient Outward K Current Can Strongly Modulate Action Potential Duration and Initiate Alternans in Human Atrium. Am J Physiol Heart Circ Physiol. 2018 Jul 20;9:958.
  • H. Ni, S. Morotti, E. Grandi. A heart for diversity: simulating variability in cardiac arrhythmia research. Front Physiol. 9:958. Review
  • Morotti, E. Grandi. Quantitative systems models illuminate arrhythmia mechanisms in heart failure: role of the Na-Ca-CaMKII-ROS feedback. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul 17:e1434. Review
  • E. Grandi@, S. Morotti, E. Pueyo, B. Rodriguez. Getting to the heart of safety Pharmacology. Front Physiol. 2018 Jun 8 9:678. Editorial
  • E. Grandi@. Keeping it short and (not so) simple: Characterizing hERG kinetics with sinusoidal waves. J Physiol. 2018 May 15;596(10):1783-1784
  • E. Grandi@ and D. Dobrev@. Non-ion channel therapeutics for heart failure and atrial fibrillation: are CaMKII inhibitors ready for clinical use? J Mol Cell Cardiol In press. Editorial.
  • F.A. Ortega, E. Grandi, T. Krogh-Madsen, D. Christini. Novel applications of dynamic clamp to cardiac arrhythmia research: Role in drug target discovery and safety pharmacology testing. Front Physiol. 2018 Jan 4;8:1099.
  • R. Vaidyanathan, H. Van Ert, K.T. Haq, S. Morotti, E. McCune, S. Esch, J. Warden, S. Abozeid, E. Grandi, L. Eckhardt. Caveolin-3 and Kir2.x Domain-Specific Interaction and Related Purkinje-Dependent Arrhythmia Mechanism. Circ Arrhythm Electrophysiol. 2018 Jan;11(1):e005800.
  • 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.
  • E. Grandi@ and D. Dobrev@. Non-ion channel therapeutics for heart failure and atrial fibrillation: are CaMKII inhibitors ready for clinical use? J Mol Cell Cardiol In press. Editorial.
  • N. Ellinwood, D. Dobrev, S. Morotti, E. Grandi@. Effects of kinetics and state dependent binding properties of IKur-targeting drugs on atrial electrophysiology. Chaos. 2017 27, 093918.
  • S. Morotti, M. Nieves-Cintrón, M.A. Nystoriak, M.F. Navedo§@, E. Grandi§@. Hyperglycemia-induced L-type Ca channel stimulation outweighs K channel suppression to impair intracellular calcium and vascular reactivity of cerebral arteries. Channels (Austin). 2017 Jul 4;11(4):340-346.
  • N.C. Surdo, M. Berrera, A. Koschinski, M. Brescia, M.R. Machado, C. Carr, Morotti, E. Grandi, P. Wright, D.M. Bers, J. Gorelik, 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.
  • M.A. Nystoriak, M. Nieves-Cintrón, T. Patriarchi, S. Morotti, E. Grandi, J. Fernandez Dos Santos, K. Forbush, F. Hofmann, K.C. Sasse, S.M. Ward, J.D. Scott, J.W. Hell, M.F. Navedo. CaV1.2 Ser1928 phosphorylation by PKA stimulates L-type Ca2+ channels and vasoconstriction during acute hyperglycemia and diabetes. Science Signaling, 10 eaaf9647. Featured in Science Signaling Podcast. Journal Issue Cover.
  • D.C. Bartos, S. Morotti, K.S. Ginsburg, E. Grandi and D.M. Bers. Ca2+-dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes. J Physiol. 2017 Apr 1;595(7):2253-2268. Highlighted by editorial.
  • E. Grandi@, M.C. Sanguinetti, D.C. Bartos, D.M. Bers, Y. Chen-Izu, N. Chiamvimonvat, H. Colecraft, B.P. Delisle, J. Heijman, M.F. Navedo, S. Noskov, C. Proenza, J.I. Vandenberg, V. Yarov-Yarovoy. Potassium channels in the heart: Structure, function and regulation. J Physiol, Special Issue on K Channels and Cardiac Electrophysiology. J Physiol. 2017 Apr 1;595(7):2209-2228. White paper. Journal Issue Cover
  • N. Chiamvimonvat, Y. Chen-Izu, C.E. Clancy, I. Deschenes, D. Dobrev, J. Heijman, L. Izu, Z. Qu, C.M. Ripplinger, J.I. Vandenberg, J. Weiss, G. Koren, E. Grandi, M.C. Sanguinetti, D. M. Bers, J. Nerbonne. Functional roles of cardiac K channels in normal and diseased heart. J Physiol, Special Issue on K Channels and Cardiac Electrophysiology. J Physiol. 2017 Apr 1;595(7):2229-2252. White paper. ​ 
  • E. Grandi@, M.M. Maleckar. Anti-arrhythmic strategies for atrial fibrillation: The role of computational modeling in discovery, development, and optimization. Pharmacology & Therapeutics. Pharmacology and Therapeutics. Pharmacol Ther. 2016 Dec;168:126-142. Review.
  • 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; 96:63-71.
  • P-C. Yang*, J.D. Moreno*, C.Y. Miyake, S.B. Vaughn-Behrens, M-T Jeng, E. Grandi, X.H.T. Wehrens, S. Noskov, C.E. Clancy. In silico prediction of drug therapy in catecholaminergic polymorphic ventricular tachycardia. JPhysiol. 2016; 594(3):567-93.
  • Y. Xie, Z. Liao, E. Grandi, Y. Shiferaw, D.M. Bers. Slow [Na]i changes and positive feedback between membrane potential and [Ca]i underlie intermittent early afterdepolarizations and arrhythmias. Circ Arrhythm Electrophysiol. 2015; 8(6):1472-1480.
  • D.C. Bartos*, E. Grandi*, C.M. Ripplinger. Ion Channels in the Heart. Comprehensive Physiology Compr Physiol 2015 Jul; 5:1423-1464. Review&.
  • Y. Chen-Izu, R. Shaw, G. Pitt, V. Yarov-Yarovoy, J. Sack, V. Maltsev, I. Deschenes, P. Mohler, H. Abriel, R. Aldrich, M. Cannell, W. Chazin, N. Chiamvimonvat, E. Grandi, T. Hund, L.T. Izu, L.S. Maier, C. Marionneau, R. Rasmussen, E.A. Sobie, C.E. Clancy, D.M. Bers. Na Channel Function, Regulation, Structure, Trafficking and Sequestration. J Physiol. 2015 Mar 15;593(6):1347-60.
  • J.A. Negroni, S. Morotti, E.C. Lascano, A.V. Gomes, E. Grandi, J.L. Puglisi, D.M. Bers. Modeling beta-adrenergic effects on cardiac contraction-relaxation in an integrated rabbit ventricular myocytes model. J Mol Cell Cardiol. 2015 Feb 25;81:162-175.
  • A.G. Edwards, E. Grandi, J.E. Hake, S. Patel, P. Li, B.D. Westenbrink, J. H. Omens, J.H. Brown, D.M. Bers, A.D. McCulloch. Non-equilibrium reactivation of the Na current drives early afterdepolarizations in the mouse ventricle. 2014 Sep 18. pii: CIRCEP.113.001666.
  • E. Grandi@, A.G. Edwards, A.W. Herren, D.M. Bers. CaMKII comes of age in cardiac health and disease. Front Pharmacol, 2014. Editorial&.
  • E. Grandi@ and A.W. Herren. CaMKII-dependent regulation of cardiac Na homeostasis. Front Pharmacol. 2014 Mar 10;5:41. Review&.
  • 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.
  • Y. Xie, E. Grandi, D.M. Bers, D. Sato. Protocol dependence of action potential wave dynamics in cardiac tissue. Europace 2014 Mar;16(3):452-7.
  • J.D. Moreno*, P-C. Yang*, J.R. Bankston, E. Grandi, D.M. Bers, R.S. Kass, C.E. Clancy. Ranolazine for congenital and acquired late INa linked arrhythmias: in silico pharmacologic screening. Circ Res. 2013 Sep 13;113(7):e50-61.
  • A.W. Herren, D.M. Bers, E. Grandi@. Post-translational Modifications of the Cardiac Na Channel. Contribution of CaMKII-Dependent Phosphorylation to Acquired Arrhythmias. Am J Physiol Heart Circ Physiol. 2013 Aug 15;305(4):H431-45. Review&.
  • Y. Xie, E. Grandi, Puglisi J., D. Sato, D.M. Bers. β-Adrenergic Stimulation Activates Early Afterdepolarizations Transiently via Kinetic Mismatch of PKA targets. J Mol Cell Cardiol. 2013 May; 58:153-61.
  • S. Morotti*, E. Grandi*, A. Summa, K.S. Ginsburg, D.M. Bers. Theoretical Study of L-type Ca Current Inactivation Kinetics during Action Potential Repolarization and Early Afterdepolarizations. J Physiol. 2012 Sep 15;590(Pt 18):4465-81.
  • D.M. Bers and E. Grandi. Human Atrial Fibrillation: insights from computational electrophysiological models. Trends Cardiovasc Med., 2011 Jul;21(5):145-150. Review&.
  • E. Grandi, A.J. Workman, and S.V. Pandit. Altered Excitation-Contraction Coupling in Human Chronic Atrial Fibrillation. JAFIB, 2012 Apr;2(10). Review&.
  • E. Grandi*, S.V. Pandit*, N. Voigt*, A.J. Workman, D. Dobrev, J. Jalife§, and D.M. Bers§. Human Atrial Action Potential and Ca Model: Sinus Rhythm and Chronic Atrial Fibrillation. Circ Res, 2011; 109:1055-66. Highlighted in the Circulation Research thematic synopsis on cardiac arrhythmias in the top 10 downloaded articles (Circ Res. 2012;111:e178-e202).
  • L. Wu, J. Ma, H. Li, C. Wang, E. Grandi, P. Zhang, A. Luo, D.M. Bers, J.C. Shryock, L. Belardinelli. Late sodium current contributes to the reverse rate-dependent effect of IKr inhibition on ventricular repolarization. Circulation, 2011 Apr 26;123(16):1713-20.
  • S. Wagner, H.M. Ruff, S.L. Weber, S. Bellmann, T. Sowa, T. Schulte, E. Grandi, D.M. Bers, J. Backs, L. Belardinelli, and L. S. Maier. ROS-activated Ca/calmodulin kinase IIδ is required for late INa augmentation leading to cellular Na and Ca overload. Circ Res, 2011 Mar 4;108(5):555-65.
  • 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.
  • E. Grandi, F.S. Pasqualini, D.M. Bers. A novel computational model of the human ventricular action potential and Ca transient. J Mol Cell Cardiol. 2010 Jan;48(1):112-21. Recommended by [Faculty of 1000] http://f1000.com/13121964.
  • D.M. Bers and E. Grandi. CaMKII Regulation of Cardiac Ion Channels. J Cardiovasc Pharmacol. 2009 Sep; 54(3):180-187. Review&.
  • S. Wagner, E. Hacker, E. Grandi, S.L. Weber, N. Dybkova, S. Sossalla, T. Sowa, L. Fabritz, P. Kirchhof, D.M. Bers, L.S. Maier. Ca/Calmodulin Kinase II Differentially Modulates Potassium Currents. Circ Arrhythm Electrophysiol. 2009 Jun;2(3):285-94.
  • E. Grandi, F.S. Pasqualini, C. Pes, C. Corsi, A. Zaza, S. Severi. Theoretical investigation of action potential duration dependence on extracellular Ca in human ventricular myocytes. J Mol Cell Cardiol. 2009 Mar;46(3):332-42.
  • E. Grandi*, M. Govoni*, S. Furini*, S. Severi, E. Giordano, A. Santoro, S. Cavalcanti. Induction of NO synthase 2 in ventricular cardiomyocytes incubated with conventional bicarbonate dialysis bath. Nephrol Dial Transplant. 2008 Jul;23(7):2192-7.
  • A. Santoro, E. Mancini, G. London, L. Mercadal, H. Fessy, B. Perrone, L. Cagnoli, E. Grandi, Severi S., Cavalcanti S. Patients with Complex Arrhythmias During and after Haemodialysis Suffer from Different Regimens of Potassium Removal. Nephrol Dial Transplant. 2008 Apr; 23(4):1415-21.
  • S. Severi*, E. Grandi*, C. Pes, F. Badiali, F. Grandi, A. Santoro. Calcium and Potassium Changes During Haemodialysis alter Ventricular Repolarization Duration: in vivo and in Silico Analysis. Nephrol Dial Transplant. 2008 Apr;23(4):1378-86.
  • E. Grandi, J.L. Puglisi, S. Wagner, L.S. Maier, S. Severi, D.M. Bers. Simulation of Ca-Calmodulin-Dependent Protein Kinase II on Rabbit Ventricular Myocyte Ion Currents and Action Potentials. Biophys J. 2007 Dec 1; 93(11):3835-47.
  • S. Vecchietti, E. Grandi, S. Severi, I. Rivolta, C. Napolitano, S.G. Priori, S. Cavalcanti. In silico assessment of Y1795C and Y1795H SCN5A mutations: implication for inherited arrhythmogenic syndromes. Am J Physiol Heart Circ Physiol. 2007 Jan; 292(1):H56-65.
  • S. Severi, A. Ciandrini, E. Grandi, S. Cavalcanti, S. Bini, F. Badiali, A. Gattiani, L. Cagnoli. Cardiac response to hemodialysis with different cardiovascular tolerance: heart rate variability and QT interval analysis. Hemodial Int. 2006 Jul; 10(3):287-93. 

(*equal contribution, §shared senior author, @corresponding author, &invited)