Cellular architecture of cardiovascular disease

To identify and develop therapeutics for cardiovascular disease, we first need to understand the cellular and molecular changes that occur in the diseased heart. In the CVDi, we generate large-scale human-focused datasets that can be used to further understand disease biology and to identify genes and pathways that could be used for therapeutic development, biomarkers, and diagnostic tools. 

Our researchers and their collaborators use a combination of:

• -omics
• high content imaging
• gene editing
• specialized cellular models and functional readouts
• animal models 

to generate and test hypotheses and validate potential therapeutic targets identified through genetic studies, with the ultimate goal of finding treatments for heart disease.

Current work includes:

• In collaboration with Broad's Center for the Development of Therapeutics (CDoT), carrying out high throughput perturbation screens on genes identified in large genetic association studies or other human datasets, using key cell types found in the heart
• Understanding the cell type-specific transcriptional and epigenetic changes that occur in relevant cell types in the diseased human heart
• Developing and using complex in vitro and in vivo models to test the effects of manipulating genes and pathways on cell and tissue function
• Assessing and validating genes and targets of interest in in vitro disease models, using iPSC-derived cardiomyocytes, primary fibroblasts, and vascular smooth muscle cells