MD, 1996 - Technion, Israel
PhD, 1999 - Technion, Israel
Human iPSC-derived cardiomyocytes for disease modeling, drug testing, and regenerative medicine
Research in the Gepstein laboratory focuses on utilization of the emerging pluripotent stem cells technologies for several cardiovascular research fields, including: (1) the emerging field of cardiovascular regenerative medicine (for infarct repair and conduction system regeneration), (2) drug screening and discovery, and (3) cardiac disease modeling. For the latter application, human induced pluripotent stem cells (hiPSCs) are established from patients with different types of inherited cardiomyopathies (such as dilated, hypertrophic and metabolic cardiomyopathies) or arrhythmogenic syndromes (such as the long QT syndrome and catecholaminergic polymorphic ventricular tachycardia - CPVT). These disease states may lead to the development of malignant arrhythmias and sudden cardiac death in otherwise healthy individuals. The different patient-specific hiPSCs lines generated are coaxed to differentiate into cardiomyocytes and even to specific cardiomyocyte subtypes (pacemaker, atrial, and ventricular cells), which are then characterized using detailed molecular, structural, and functional studies. These studies are expected to provide new mechanistic insights into inherited cardiac disorders, to allow optimization of patient-specific therapies (personalized medicine), and to facilitate development of new therapies.
Nussinovitch U and Gepstein L. 2015. Optogenetics for in vivo cardiac pacing and resynchronization therapies. Nature Biotechnology. 33, 750-4.
Shinnawi R, Huber I, Maizels L, Shaheen N, Gepstein A, Arbel G, Tijsen AJ and Gepstein L. 2015. Monitoring human induced pluripotent stem cells derived cardiomyocytes with genetically-encoded calcium and voltage fluorescent reporters. Stem Cell Reports.
Zwi-Dantsis L, Huber I, Habib M, Winterstern A, Gepstein A, Arbel G, and Gepstein L. 2013. Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients. Eur Heart J. 34, 1575-1586.
Caspi O, Huber I, Gepstein A, Arbel G, Maizels L, Boulos M, and Gepstein L. 2013. Modeling of arrhythmogenic right ventricular cardiomyopathy with human induced pluripotent stem cells. Circ. Cardiovasc. Genet. 6, 557-568.
Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O, Winterstern A, Feldman O, Gepstein A, Arbel A, Hammerman H, Boulos M, and Gepstein L. 2011. Modelling the long QT syndrome with induced pluripotent stem cells. Nature. 471, 225-229.
Human heart cell generated from induced pluripotent stem cells.