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. Lei, CL, Clark, AP, Clerx, M, Wei, S, Bloothooft, M, de Boer, TP et al.. Resolving artefacts in voltage-clamp experiments with computational modelling: an application to fast sodium current recordings. bioRxiv. 2024; :. doi: 10.1101/2024.07.23.604780. PubMed PMID:39091746 PubMed Central PMC11291073.
  2. Clark, AP, Wei, S, Christini, DJ, Krogh-Madsen, T. Single-cell ionic current phenotyping elucidates non-canonical features and predictive potential of cardiomyocytes during automated drug experiments. J Physiol. 2024;602 (20):5163-5178. doi: 10.1113/JP285120. PubMed PMID:38747042 PubMed Central PMC11493530.
  3. Clark, AP, Krogh-Madsen, T, Christini, DJ. Stem cell-derived cardiomyocyte heterogeneity confounds electrophysiological insights. J Physiol. 2024;602 (20):5155-5162. doi: 10.1113/JP284618. PubMed PMID:38723234 PubMed Central PMC11493526.
  4. Clark, AP, Wei, S, Fullerton, K, Krogh-Madsen, T, Christini, DJ. Single-cell ionic current phenotyping explains stem cell-derived cardiomyocyte action potential morphology. Am J Physiol Heart Circ Physiol. 2024;326 (5):H1146-H1154. doi: 10.1152/ajpheart.00063.2024. PubMed PMID:38488520 PubMed Central PMC11380975.
  5. Fullerton, KE, Clark, AP, Krogh-Madsen, T, Christini, DJ. Optimization of a cardiomyocyte model illuminates role of increased INa,L in repolarization reserve. Am J Physiol Heart Circ Physiol. 2024;326 (2):H334-H345. doi: 10.1152/ajpheart.00553.2023. PubMed PMID:38038718 .
  6. Clark, AP, Wei, S, Fullerton, K, Krogh-Madsen, T, Christini, DJ. Rapid ionic current phenotyping (RICP) identifies mechanistic underpinnings of iPSC-CM AP heterogeneity. bioRxiv. 2023; :. doi: 10.1101/2023.08.16.553521. PubMed PMID:37645815 PubMed Central PMC10461967.
  7. Clark, AP, Clerx, M, Wei, S, Lei, CL, de Boer, TP, Mirams, GR et al.. Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings. Europace. 2023;25 (9):. doi: 10.1093/europace/euad243. PubMed PMID:37552789 PubMed Central PMC10445319.
  8. 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.
  9. 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.
  10. 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 .
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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 .
  18. 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.
  19. 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.
  20. 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.
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