Our team studies novel mechanisms of mammalian cardiac regeneration and repair following injury, a major challenge in current biomedical research (Tzahor and Poss, Science 2017) using mouse, rats and pigs’ models. We are focusing on the role of NRG1-ErbB2 signaling pathway in cardiac regeneration (D’Uva et al., NCB 2015; Aharonov et al., NCB 2020). We also study the cardiac microenvironment as a mean to enhance the regenerative potential of the heart (Yahalom et al., eLIFE 2015). We revealed that the proteoglycan Agrin can serve as an inducer of mammalian heart regeneration, with a great therapeutic potential for the treatment of ischemic heart disease (Bassat et al., Nature 2017; Sarig et al., Circulation 2019). Current studies revealed the therapeutic effects of Agrin, whose administration into injured heart of pigs elicits a significant regenerative response (Baehr et al., Circulation 2020). Our studies contribute towards improving current strategies to treat heart disease in human.