Objective The study of several genetic disorders is hampered by the lack of suitable in vitro human models. We hypothesize that the generation of patient-specific induced pluripotent stem cells (iPSCs) will allow the development of disease-specific in vitro models; yielding new pathophysiologic insights into several genetic disorders and offering a unique platform to test novel therapeutic strategies. In the current proposal we plan utilize this novel approach to establish human iPSC (hiPSC) lines for the study of a variety of inherited cardiac disorders. The specific disease states that will be studied were chosen to reflect abnormalities in a wide-array of different cardiomyocyte cellular processes.These include mutations leading to:(1) abnormal ion channel function (“channelopathies”), such as the long QT and Brugada syndromes;(2) abnormal intracellular storage of unnecessary material, such as in the glycogen storage disease type IIb (Pompe’s disease); and(3) abnormalities in cell-to-cell contacts, such as in the case of arrhythmogenic right ventricular cardiomyopathy-dysplasia (ARVC-D). The different hiPSC lines generated will be coaxed to differentiate into the cardiac lineage. Detailed molecular, structural, functional, and pharmacological studies will then be performed to characterize the phenotypic properties of the generated hiPSC-derived cardiomyocytes, with specific emphasis on their molecular, ultrastructural, electrophysiological, and Ca2+ handling properties.These studies should provide new insights into the pathophysiological mechanisms underlying the different familial arrhythmogenic and cardiomyopathy disorders studied, may allow optimization of patient-specific therapies (personalized medicine), and may facilitate the development of novel therapeutic strategies.Moreover, the concepts and methodological knowhow developed in the current project could be extended, in the future, to derive human disease-specific cell culture models for a plurality of genetic disorders; enabling translational research ranging from investigation of the most fundamental cellular mechanisms involved in human tissue formation and physiology through disease investigation and the development and testing of novel therapies that could potentially find their way to the bedside Fields of science medical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health scienceshealth sciencespersonalized medicinemedical and health sciencesbasic medicinephysiology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2010-StG_20091118 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY Address Senate building technion city 32000 Haifa Israel See on map Activity type Higher or Secondary Education Establishments Principal investigator Lior Gepstein (Prof.) Administrative Contact Mark Davison (Mr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY Israel EU contribution € 1 500 000,00 Address Senate building technion city 32000 Haifa See on map Activity type Higher or Secondary Education Establishments Principal investigator Lior Gepstein (Prof.) Administrative Contact Mark Davison (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
