Cardiac Development and Reprogramming
The mammalian heart is the first functional organ to form in the embryo and emerges from a simple cardiac tube that is transformed into a sophisticated four-chambered muscular pump. At the molecular level, this fascinating process is tightly orchestrated by gene regulatory networks. These gene networks are themselves under the control of cis-regulatory modules encoded in our genomes and known as “transcriptional enhancers”. Enhancers drive the tissue- and cell type-specific expression patterns of genes and on the linear chromosome can be located hundreds of thousands of base-pairs away from the transcriptional start site. Recent epigenomic profiling studies predict the presence of up to a million of such transcriptional enhancers in human genomes.
Our lab uses innovative approaches in molecular genetics, functional genomics and genome editing to study how developmental cardiac genes are controlled at the cis-regulatory level. For example, we are using CRISPR/Cas9 in mouse embryos for functional dissection of the cardiac enhancer landscapes of key transcription factor (TF) genes essential for heart development. We are further exploring the regulation of these TFs in the cardiac reprogramming process which holds therapeutic potential for the regeneration of heart muscle in context of ischemic heart disease.
The identification of cardiac enhancers and understanding of their regulatory relationships and cellular specificities will be critical to establish accurate mechanistic links between genomic mutations, cardiac development and congenital heart disease.
More information about our group can be found on our laboratory website.