Ofer Binah, PhD
Professor of Physiology
PhD, 1980 - Technion, Israel
Investigating inherited cardiac pathologies using iPSC-derived cardiomyocytes generated from the patients' somatic cells.
Dilated Cardiodystrophinopathy caused by mutations in dystrophin (DYS) is a dilated cardiomyopathy (DCM) occurring in 70-100% of DYS patients, and is a major cause of death due to end-stage heart failure in Duchenne Muscular Dystrophy (DMD). Despite major advances in understanding DYS-DCM, to date there are no cures for DMD, except for heart failure medications, and therefore new therapeutic approaches are urgently required. Our working hypothesis is that any therapy of interest should be individually tailored according to the gene mutation and protein defect, and therefore has to be tested first in vitro in mutated cardiomyocytes from the affected individual. Accordingly, our goals are to: (1) generate an in vitro system for investigating the mechanisms of inherited cardiodystrophinopathies, using iPSC-derived cardiomyocytes (iPSC-CM) generated from the patients' somatic cells; (2) utilize mutated iPSC-CM to test the efficacy of existing and novel drugs and identify new therapeutic targets.
Novak A, Barad L, Lorber A, Gherghiceanu M, Reiter I, Eisen B, Eldor L, Itskovitz-Eldor J, Eldar M, Arad M, and Binah O. 2015. Functional abnormalities in iPSC-derived cardiomyocytes generated from CPVT1 and CPVT2 patients carrying ryanodine or calsequestrin mutations. J. Cell Mol. Med. 19, 2006-18.
Ben-Ari M, Shick R, Barad L, Novak A, Ben-Ari E, Lorber A, Itskovitz-Eldor J, Rosen R, Weissman A, and Binah O. 2014. From beat rate variability in induced pluripotent stem cell-derived pacemaker cells to heart rate variability in human subjects. Heart Rhythm. 11, 1808-18.
Binah O, Weissman A, Itskovitz-Eldor J, and Rosen MR. 2013. Integrating beat rate variability from single cells to hearts. Heart Rhythm. 10, 928-32.
Novak A, Barad L, Zeevi-Levin N, Shick R, Shtrichman R, Lorber A, Itskovitz-Eldor J, and Binah O. 2012. Cardiomyocytes generated from CPVTD307H patients are arrhythmogenic in response to β-adrenergic stimulation. J. Cell Mol. Med. 16, 468-82.
Mandel Y, A Weissman A, Novak A, Meiry G, Goldberg S, Lorber A, Rosen MR, Itskovitz-Eldor J, and Binah O. 2012. Human embryonic and induced pluripotent stem cells-derived cardiomyocytes exhibit beat rate variability and power-law behavior. Circulation 125, 883-93.
Generating and investigating the functional properties of cardiomyocytes differentiated from induced Pluripotent Stem Cells (iPSC) generated from hair keratinocytes.
Upper row: Generation of iPSC-derived cardiomyocytes (iPSC-CM) from hair keratinocytes. Lower row: Left panel: Transmembrane action potential recorded from spontaneously firing iPSC-CM by means of the patch clamp technique. Middle panel: Simultaneous recordings of calcium transients and contractions from iPSC-CM. Right panel: Extracellular electrograms recorded from a contracting Embryoid Body (EB) by means of the Micro-Electrode Array (MEA) set-up.