Experimental approaches are needed to define molecular and physiological mechanisms underlying the genetic associations with CVD that can be targeted therapeutically. In proof-of-principle functional studies, we are conducting targeted experimentation of promising hypotheses identified by Genetic Discovery.
In collaboration with the Wellcome Trust Sanger Institute, we are using human induced pluripotent stem cells (iPSC) to derive cell types that play key roles in CVD aetiology, allowing characterisation of functional effects of genetic risk variants in the appropriate cellular and environmental context.
We are conducting genotype-directed deep phenotyping of healthy volunteers who carry pivotal CVD variants versus those who do not. The concept is to identify molecular phenotypes in a causal CVD pathway that differ between the relevant genotypic groups by using genetic information to help recreate informative biological gradients. For these studies, we are recruiting volunteers via recall-able bioresources, such as the Cambridge NIHR BioResource.
In collaboration with other teams, we are using genome editing techniques in cell types with relevance to CVD pathophysiology to advance the mechanistic understanding of candidate functional variants.
To find out more about this research theme, please visit the Integrative Human Genomics team website.