My lab is focused on intracellular signalling pathways that are critical mediators of cardiomyocyte biology. Previously, my work has revealed non-canonical functions for the JAK/STAT signalling pathway in the regulating cytoskeletal remodelling in cardiomyocytes, and the role of Mitogen Activated Protein Kinases (MAPK) in cardiomyocyte hypertrophy stimulated by inflammatory cytokines. In this presentation, I will discuss current unpublished work investigating novel flavonol compounds that target signalling from the stress-activated protein kinase members (JNK and p38MAPK) of the MAPK family to elicit cyto- and cardio-protective benefits. This project is an interdisciplinary collaboration between groups at LaTrobe, RMIT, Howard Florey and Bio21 Institutes that has sought to uncover the mode of action of these novel cardioprotective flavonols. We demonstrated that JNK and p38MAPK are critical mediators of cardiomyocyte death and revealed that the dual-inhibition of these kinases is involved in flavonol-mediated cardioprotection in a sheep model of ischemia/reperfusion injury. I will also discuss the specific mechanism leading to JNK and p38MAPK inhibition. Our study reinforces the proinjurious consequences of JNK and p38MAPK activated in myocardial ischemia/reperfusion and provides mechanistic insights into regulation of cardiomyocyte death that are highly relevant in the development of novel therapies for cardioprotection.