Advancing Epigenetics Towards Systems Biology

Dirk Paul

University of Cambridge

Functional genomics of cardiovascular disease

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dirk paul

Our goal is to identify and validate causal pathways in cardiovascular disease. Large-scale genome-wide association studies (GWAS) have been very fruitful in pinpointing genomic regions that associate with the disease. However, the precise mechanism underlying most of these genetic associations remains elusive. To this end, we use both computational and experimental approaches to expose new mechanisms leading to atherosclerosis, the major cause of cardiovascular disease. We apply cutting-edge technology, including human induced pluripotent stem cells and CRISPR/Cas9 (epi-)genome editing, to elucidate the biological underpinnings of candidate causal genes and pathways. In parallel, we conduct recall-by-genotype studies, in which individuals with a potential functional genetic variant are called back for additional hypothesis-driven phenotyping. Our efforts, which integrate genetic epidemiology, functional genomics and epigenomics, as well as clinical medicine, facilitate a better understanding of the aetiology of cardiovascular disease to inform the development of new therapeutics.

Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
Human Genetics, Wellcome Trust Sanger Institute.