We focus on three primary cardiomyopathies: Hypertrophic (HCM), Dilated (DCM), and Arrhythmogenic (ACM) Cardiomyopathies. These diseases develop underlying structural and molecular defects, (dilation of chamber, reduction in chamber size, fibrofatty replacement of muscle cells), ultimately weakening the heart and increasing the risk of heart failure.
Myocardial fibrosis plays a key role in many heart diseases, including cardiomyopathies, heart attacks, and chronic conditions. To address this, we are developing Cardioid models to study and screen for fibrotic remodeling - when damaged tissues attempt to heal themselves- enabling a better understanding and treatment of heart disease.
Our electrophysiology assays directly measure the electrical activity of cardiac cells and tissues. Examples are a multielectrode array (MEA) which can be paired with an optogenetic pacer to control beat rates.
Reporter lines were engineered using genetics and fluorescent proteins that label cell types (cardiomyocytes, cardiac endothelial cells, and cardiac fibroblasts)- allowing us to track, measure, and control Cardioid function.
The contraction analysis we use measures a cell or tissue’s ability to contract. This can be done through calcium transient (fluorescent calcium reporter) or video-based analysis of beating behavior.
We have developed an assay for fibrosis, a key element of many heart diseases, that allows us to measure its impact.
Histology and 3D reconstruction allow us to visualize and measure the structural features of cells and tissues, providing key insights into their structure and function. 3D reconstruction of a Cardioid allows for a comprehensive analysis of chamber-level defects.
Adeno-associated virus (AAV)/gene therapy optimization is a laboratory approach to enhance and refine the delivery, spatial expression, and efficacy of therapeutic genes in the 3D chamber context of a Cardioid.