Regulation of plasticity in cardiovascular health and disease
Tissue homeostasis and regeneration after injury rely on mobilisation of tissue resident stem and progenitor cells or de-differentiation of functional cell types. Our group investigates the regulation of such cell plasticity in the cardiovascular system and how this is perturbed in disease. In particular, we study vascular smooth muscle cells (VSMCs) and how these cells contribute to the development of atherosclerosis, the disease underlying heart attack and stroke. VSMCs exist in a contractile, quiescent state in healthy arteries, but can downregulate this phenotype in response to injury and inflammation. The resulting de-differentiated state is characterised by widespread changes in gene expression leading to perturbed extracellular matrix remodelling, proliferation and migration. Using genetic disease models, single cell approaches and global epigenetic profiling, we study how these gene expression programs are regulated and impact on phenotypic plasticity in development, tissue homeostasis and disease.