Ofer Binah, PhD
Professor of Physiology
PhD, 1980 - Technion, Israel
Investigating the inherited cardiac disease Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) using cardiomyocytes generated from patient-derived hair and dermal fibroblasts
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a lethal inherited arrhythmia characterized by adrenergically-mediated polymorphic ventricular tachycardia (PVT). The clinical phenotype of the disease in an 11-year old boy belonging to a Bedouin tribe residing in northern Israel is illustrated by the exercise-induced PVT detected using an electrocardiogram (ECG) (see Figure). The focus of research in my laboratory is to investigate the mechanisms underlying CPVT. To this end, hair keratinocytes and dermal fibroblasts from CPVT patients are induced to become pluripotent stem cells (iPSC) and then differentiated into cardiomyocytes (iPSC-CM). The iPSC-CM are studied by monitoring various features: [Ca2+]i transients and contractions; extracellular electrograms using the Micro-Electrode-Array (MEA) system; action potentials and key ion currents related to arrhythmogenesis, for example the transient inward current (ITi) measured using the patch clamp technique. We are taking three complementary approaches: 1, generation and study of iPSC-CM from ryanodine (RyR2)- and calsequestrin-mutated CPVT patients; 2, investigating the Excitation-Contraction (E-C) coupling machinery and adrenergic responsiveness of CPVT-iPSC-CM; and 3, characterizing the responsiveness of CPVT-iPSC-CM to anti-arrhythmic drugs.
Electrocardiogram (ECG) readouts before and after exercise from an 11-year old boy with CVPT from the Bedouin tribe. [A] Baseline ECG strip (lead 3) showing sinus bradycardia (HR = 55 bpm). The boy was treated with β blocker (Deralin) + calcium channel blocker (Verapamil). [B] An ECG strip (lead 3) during an exercise test showing polymorphic ventricular tachycardia (PVT).
Mandel Y, Weissman A, Schick R, Barad L, Novak A, Meiry G, Goldberg S, Lorber A, Rosen MR, Itskovitz-Eldor J, Binah O. 2012. Human embryonic and induced pluripotent stem cell-derived cardiomyocytes exhibit beat rate variability and power-law behavior. Circulation 125, 883-93.
Novak A, Barad L, Zeevi-Levin N, Shtreichman R, Gherghiceanu M, Popescu LM, Lorber A, Itskovitz-Eldor J, Binah O. 2012. CPVT-specific cardiomyocytes generated from induced pluripotent stem cells are arrhythmogenic. J Cell Mol Med 16, 468-82.
Ertracht O, Liani E, Bachner N, Bar-Am O, Ovcharenko E, Awad H, Barac Y, Frolov L, Amit T, Abassi Z, Adam D, Youdim M, Binah O. 2011. The cardioprotective efficacy of TVP1022 in a rat model of myocardial infarction: Involvement of the glycogen synthase kinase 3β pathway and the mitochondrial permeability transition pore. Br J Pharmacol 163, 755-69.