Gareth Purvis

Research project title: Mechanisms behind residual risk in cardiovascular disease

Project summary

My project is to understand the genetic and molecular mechanism behind residual risk in cardiovascular disease. Inflammation (hs-CRP) is now seen as a better indicator for disease risk in CVD than LDL in patients on optimal lipid lowering interventions. To achieve these outcomes I will use two complimentary models: Firstly using complex in vivo models of hypercholesterolemia to mimic human pathology and secondly using human iPSC organoid models to attribute genome wide associations to transcription regulators and epigenetic modifications in a cell type specific manner, to understand if there is a heritable component to residual risk.

The project brings together my experience of in vivo models of cardiometabolic disease and innate immunity; with the desire to learn new skills (human iPSC organoid models and large genetic data set integration).  Having the continued mentorship of Prof Keith Channon along with other colleagues in the Centre for Human Genetics (Prof Chris O’Callaghan) and the MRC WIMM (Prof Adam Mead and Prof Beth Psaila) will bring together expertise on human pathology in cardiovascular disease, stem cell biology, iPSC organoids and epigenetic regulation of gene transcription. This will allow us to create genome wide maps of chromatin accessibility and gene expression in heterogeneous cell types in human iPSC organoids.