Hypertrophic cardiomyopathy (HCM) is an inherited disease involving hypertrophy or thickening of the heart muscle. It is the leading cause of sudden cardiac death in young adults and athletes. Mutations in several cardiac structural proteins have been identified as the cause for this condition, but the mechanisms by which cardiomyocytes undergo hypertrophy in response to these structural protein mutations is unclear. One of the proposed mechanisms that regulate cardiomyocyte hypertrophy are the factors secreted during endothelial cell-cardiomyocyte crosstalk. While there is extensive knowledge regarding several classes of factors identified in endothelial cell-cardiomyocyte crosstalk, the specific role of microRNAs remains unclear. Because of their ability to control gene expression of various factors, microRNAs could be a key target in regulating disease states such as HCM. The objective of my project is to identify and target differentially expressed miRNAs between healthy and HCM states in order to mitigate progression of cardiomyocyte hypertrophy. Using novel microfluidic platforms for modeling vascularized tissues, we will optimize culture conditions for hiPSC-derived cardiomyocytes and endothelial cells, providing us with greater physiological fidelity than standard in vitro techniques. With no specific treatment options, investigating the role of microRNAs in endothelial cell-cardiomyocyte crosstalk could allow the possibility of using miRNAs as therapeutics to improve disease management and outcomes for patients with HCM.