Reactivating ancestral heart regeneration programs in mammals
Heart failure has a poor prognosis and affects over 38 million patients worldwide. Humans have only a limited capacity to regenerate cardiomyocytes following injury. However, zebrafish possess a remarkable capacity to completely and efficiently regenerate the heart. Our goal is to identify and understand endogenous mechanisms of heart regeneration in zebrafish, and apply them to humans to promote heart regeneration following injury.
To identify mechanisms that promote heart regeneration, we have conducted extensive systems-based bioinformatic and proteomic analyses to identify genes/proteins that are (i) upregulated during heart regeneration in zebrafish, but (ii) fail to become upregulated during mouse heart regeneration. We propose that these genes underlie the ability of zebrafish to regenerate their hearts. We have initially focussed our research on proteins that are secreted in injured hearts and our research efforts are exploring how these proteins stimulate cardiomyocyte dedifferentiation, proliferation and redifferentiation.
Research Methods and Objectives
Our systems-based analyses utilise data from humans and mouse; however, we are testing our hypotheses in a tractable zebrafish model system. Briefly, zebrafish have an unparalleled capacity for heart regeneration. Therefore, we experimentally induce cardiomyocyte death and assess regeneration potential.