Eleonora Grandi

image of Eleonora Grandi

ASSISTANT PROFESSOR

Departments

Pharmacology - Medicine

Offices and Labs

Tupper Hall 2427
(530) 752-4780

Profile Introduction

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

Degrees

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

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.

CBS Grad Group Affiliations

Molecular, Cellular, and Integrative Physiology

Specialties / Focus

Molecular, Cellular, and Integrative Physiology
  • Cardiorespiratory Physiology
  • Cellular Physiology
  • Molecular Physiology

Publications

  • Complete List of Publications

    ·       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. Review. In press.

    ·       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. White paper. In press.

    ·       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)