David Christini, Ph.D.

Professor of Physiology and Biophysics

  • Professor of Biomedical Engineering in Medicine (primary appointment)
  • Professor of Computational Biomedicine in the Institute for Computational Biomedicine
  • Vice Dean, Weill Cornell Graduate School of Medical Sciences

646-962-8492

Belfer Research Building
413 E 69th Street, Room BB-512
New York, NY 10021

Lab website: http://www.christinilab.org/

Techniques

Research Areas

Member of:

Research Summary:

In our laboratory, we study cardiac electrophysiological dynamics from the cellular level to the organ level. We are primarily interested in understanding the mechanisms underlying arrhythmia initiation (from the cellular to whole-heart levels) and in developing new arrhythmia therapies. We use computational, in vitro, and clinical methods in an interdisciplinary approach that interweaves concepts from physics, biophysics, and bioengineering.

Recent Publications:

  1. Clark, AP, Wei, S, Kalola, D, Krogh-Madsen, T, Christini, DJ. An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic pro-arrhythmia mechanisms. Br J Pharmacol. 2022;179 (20):4829-4843. doi: 10.1111/bph.15915. PubMed PMID:35781252 PubMed Central PMC9489646.
  2. Ghazizadeh, Z, Zhu, J, Fattahi, F, Tang, A, Sun, X, Amin, S et al.. A dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells. iScience. 2022;25 (4):104153. doi: 10.1016/j.isci.2022.104153. PubMed PMID:35434558 PubMed Central PMC9010642.
  3. Gaur, N, Ortega, F, Verkerk, AO, Mengarelli, I, Krogh-Madsen, T, Christini, DJ et al.. Validation of quantitative measure of repolarization reserve as a novel marker of drug induced proarrhythmia. J Mol Cell Cardiol. 2020;145 :122-132. doi: 10.1016/j.yjmcc.2020.04.019. PubMed PMID:32325153 .
  4. Whittaker, DG, Clerx, M, Lei, CL, Christini, DJ, Mirams, GR. Calibration of ionic and cellular cardiac electrophysiology models. Wiley Interdiscip Rev Syst Biol Med. 2020;12 (4):e1482. doi: 10.1002/wsbm.1482. PubMed PMID:32084308 PubMed Central PMC8614115.
  5. Tsai, SY, Ghazizadeh, Z, Wang, HJ, Amin, S, Ortega, FA, Badieyan, ZS et al.. A human embryonic stem cell reporter line for monitoring chemical-induced cardiotoxicity. Cardiovasc Res. 2020;116 (3):658-670. doi: 10.1093/cvr/cvz148. PubMed PMID:31173076 PubMed Central PMC7252441.
  6. Quach, B, Krogh-Madsen, T, Entcheva, E, Christini, DJ. Light-Activated Dynamic Clamp Using iPSC-Derived Cardiomyocytes. Biophys J. 2018;115 (11):2206-2217. doi: 10.1016/j.bpj.2018.10.018. PubMed PMID:30447994 PubMed Central PMC6289097.
  7. Ortega, FA, Grandi, E, Krogh-Madsen, T, Christini, DJ. Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing. Front Physiol. 2017;8 :1099. doi: 10.3389/fphys.2017.01099. PubMed PMID:29354069 PubMed Central PMC5758594.
  8. Krogh-Madsen, T, Jacobson, AF, Ortega, FA, Christini, DJ. Global Optimization of Ventricular Myocyte Model to Multi-Variable Objective Improves Predictions of Drug-Induced Torsades de Pointes. Front Physiol. 2017;8 :1059. doi: 10.3389/fphys.2017.01059. PubMed PMID:29311985 PubMed Central PMC5742183.
  9. Brown, K, Legros, S, Ortega, FA, Dai, Y, Doss, MX, Christini, DJ et al.. Overexpression of Map3k7 activates sinoatrial node-like differentiation in mouse ES-derived cardiomyocytes. PLoS One. 2017;12 (12):e0189818. doi: 10.1371/journal.pone.0189818. PubMed PMID:29281682 PubMed Central PMC5744947.
  10. Krogh-Madsen, T, Christini, DJ. Slow [Na+]i dynamics impacts arrhythmogenesis and spiral wave reentry in cardiac myocyte ionic model. Chaos. 2017;27 (9):093907. doi: 10.1063/1.4999475. PubMed PMID:28964146 .
  11. Patel, YA, George, A, Dorval, AD, White, JA, Christini, DJ, Butera, RJ et al.. Hard real-time closed-loop electrophysiology with the Real-Time eXperiment Interface (RTXI). PLoS Comput Biol. 2017;13 (5):e1005430. doi: 10.1371/journal.pcbi.1005430. PubMed PMID:28557998 PubMed Central PMC5469488.
  12. Devenyi, RA, Ortega, FA, Groenendaal, W, Krogh-Madsen, T, Christini, DJ, Sobie, EA et al.. Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility. J Physiol. 2017;595 (7):2301-2317. doi: 10.1113/JP273191. PubMed PMID:27779762 PubMed Central PMC5374112.
  13. Brown, TR, Krogh-Madsen, T, Christini, DJ. Illuminating Myocyte-Fibroblast Homotypic and Heterotypic Gap Junction Dynamics Using Dynamic Clamp. Biophys J. 2016;111 (4):785-797. doi: 10.1016/j.bpj.2016.06.042. PubMed PMID:27558722 PubMed Central PMC5002081.
  14. Krogh-Madsen, T, Sobie, EA, Christini, DJ. Improving cardiomyocyte model fidelity and utility via dynamic electrophysiology protocols and optimization algorithms. J Physiol. 2016;594 (9):2525-36. doi: 10.1113/JP270618. PubMed PMID:26661516 PubMed Central PMC4850194.
  15. Brown, TR, Krogh-Madsen, T, Christini, DJ. Computational Approaches to Understanding the Role of Fibroblast-Myocyte Interactions in Cardiac Arrhythmogenesis. Biomed Res Int. 2015;2015 :465714. doi: 10.1155/2015/465714. PubMed PMID:26601107 PubMed Central PMC4637154.
  16. Groenendaal, W, Ortega, FA, Kherlopian, AR, Zygmunt, AC, Krogh-Madsen, T, Christini, DJ et al.. Cell-specific cardiac electrophysiology models. PLoS Comput Biol. 2015;11 (4):e1004242. doi: 10.1371/journal.pcbi.1004242. PubMed PMID:25928268 PubMed Central PMC4415772.
  17. Ortega, FA, Butera, RJ, Christini, DJ, White, JA, Dorval, AD 2nd. Dynamic clamp in cardiac and neuronal systems using RTXI. Methods Mol Biol. 2014;1183 :327-54. doi: 10.1007/978-1-4939-1096-0_21. PubMed PMID:25023319 PubMed Central PMC4880480.
  18. Groenendaal, W, Ortega, FA, Krogh-Madsen, T, Christini, DJ. Voltage and calcium dynamics both underlie cellular alternans in cardiac myocytes. Biophys J. 2014;106 (10):2222-32. doi: 10.1016/j.bpj.2014.03.048. PubMed PMID:24853751 PubMed Central PMC4052344.
  19. Maoz, A, Christini, DJ, Krogh-Madsen, T. Dependence of phase-2 reentry and repolarization dispersion on epicardial and transmural ionic heterogeneity: a simulation study. Europace. 2014;16 (3):458-65. doi: 10.1093/europace/eut379. PubMed PMID:24569901 PubMed Central PMC3934847.
  20. Hu, Z, Kant, R, Anand, M, King, EC, Krogh-Madsen, T, Christini, DJ et al.. Kcne2 deletion creates a multisystem syndrome predisposing to sudden cardiac death. Circ Cardiovasc Genet. 2014;7 (1):33-42. doi: 10.1161/CIRCGENETICS.113.000315. PubMed PMID:24403551 PubMed Central PMC4917016.
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