Cardiovascular Functional Genomics

The Ward Lab is interested in understanding the mechanisms of global transcriptional regulation, and the control of tissue-specific gene expression in the context of cardiovascular development, stress and disease. Some of the questions we are interested in include:

•  How does the same DNA sequence in virtually every cell in the body give rise to a diversity of tissue types?

•  How is the genome able to respond to perturbations in the environment?

•  What makes a genome susceptible or resistant to disease?

• Ultimately, how does the genome encode a multitude of different phenotypes?

A clue comes from the fact that the majority of the human genome is non-coding. Regulatory regions, within non-coding DNA sequence, have been shown to direct the correct spatial and temporal expression of genes. Indeed, the impact of non-coding DNA sequence has been highlighted through genotype-phenotype associations, and the study of complex traits and disease. One such disease is cardiovascular disease (CVD), which results from many contributing genetic and environmental factors. However, disentangling the effects of multiple genetic loci associated with a human phenotype, and the effect of the environment, is challenging. The ability to generate induced pluripotent stem cells (iPSCs) from easily accessible human tissue, differentiate these cells into relevant cell types, and subject them to directed perturbations, provides a powerful system to dissect the relationship between genotype and phenotype.

The goal of the Ward lab is to dissect the global role of regulatory elements, including those derived from transposable elements, in directing gene expression in healthy, stressed and disease states in CVD-relevant cell types. We use a combination of induced pluripotent stem cell technology, functional genomics, evolutionary biology and genetics approaches to tackle this problem.