Objective The quest to restore damaged organs is one of the major challenges in medicine. Recent studies in both animals and in humans suggest that the heart has a limited capacity to replenish its own cardiomyocytes (CMs) throughout life, albeit inadequate to compensate for major injuries such as acute myocardial infarction (MI). Most therapeutic research in regenerative cardiogenesis is geared toward stem cell therapy as a means to replace lost CMs associated with ischemic heart disease. Clinical data evaluating the efficacy of cell-based therapy for heart disease are relatively disappointing. This proposal encompasses multidisciplinary and novel approaches to study the molecular and cellular mechanisms that govern the proliferation, differentiation and dedifferentiation of endogenous CMs, combining developmental-, systems- and cell-biology methodologies in vitro and in vivo, in chick, rodent, and human tissue samples. First, we will perform combinatorial perturbations of signaling pathways in chick embryos, focusing primarily on the FGF-ERK pathway, to investigate the molecular switch between cardiac progenitors and CMs (Aim 1). Because adult CMs have limited proliferative capacity, mainly due to mechanical constraints, in Aim 2, we will apply state-of-the-art techniques in cell biology, to determine whether specific mechno-transduction stimuli can prime the proliferation of differentiated CMs. In order to gain deeper insights into the capacity of adult CMs to renew themselves under normal and pathological conditions, in Aim 3, we will employ a novel cell lineage methodology in mouse and human tissue, based on information encoded in genome. Using this methodology, we hope to shed light on the maintenance, renewal and regenerative capacities of adult CMs in vivo. The expected outcome will be a significantly greater understanding of the bidirectional transition from proliferating cardiac progenitors into differentiated CMs, in embryonic and adult hearts. Fields of science natural sciencesbiological sciencescell biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineembryologynatural sciencesbiological sciencesgeneticsgenomes 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-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution WEIZMANN INSTITUTE OF SCIENCE EU contribution € 1 500 000,00 Address HERZL STREET 234 7610001 Rehovot Israel See on map Activity type Higher or Secondary Education Establishments Principal investigator Eldad Tzahor (Prof.) Administrative Contact Gabi Bernstein (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all WEIZMANN INSTITUTE OF SCIENCE Israel EU contribution € 1 500 000,00 Address HERZL STREET 234 7610001 Rehovot See on map Activity type Higher or Secondary Education Establishments Principal investigator Eldad Tzahor (Prof.) Administrative Contact Gabi Bernstein (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
