We focus on three primary cardiomyopathies: Hypertrophic (HCM), Dilated (DCM), and Arrhythmogenic (ACM) cardiomyopathies. These diseases involve structural and molecular defects, such as chamber dilation, reduced size, and fibrofatty replacement of cardiac muscle cells, ultimately weakening the heart and increasing heart failure risk. Our models replicate these conditions, enabling the development of novel therapies that target the underlying molecular and structural mechanisms of these diseases.
We model drug-induced heart muscle thickening (hypertrophy) and related conditions, as well as other drug-induced effects, such as cardiotoxicity from chemotherapy (Cardio-Oncology). These models provide a valuable platform for assessing the impact of potential therapies, enabling the identification and development of drugs that can mitigate or prevent adverse cardiac effects.
Myocardial fibrosis plays a key role in many heart diseases, including cardiomyopathies, myocardial infarction, and chronic conditions such as hypertension and diabetes. To address this, we are developing Cardioid models to study and screen for fibrotic remodeling, where damaged tissues attempt to heal. These models enable the identification and evaluation of potential drug candidates, with the goal of mitigating or preventing the development of myocardial fibrosis and post-injury cardiac remodeling.
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.