Dr Murray Clarke has been awarded a British Heart Foundation Senior Research Fellowship to investigate how cell type-specific necrosis drives inflammation in atherosclerosis and other chronic inflammatory diseases.
Murray Clarke has previously shown that death of vascular smooth muscle cells (VSMCs) leads to unstable atherosclerotic plaques – the primary cause of heart attacks and stroke. VSMC necrosis is incredibly inflammatory and drives plaque growth, whilst necrosis of other cell types is relatively silent. However, the mechanisms underlying such specificity were previously unknown. Murray’s work, recently published in Immunity, has revealed that an intracellular form of a receptor that usually resides on the cell surface binds the inflammatory cytokine IL-1α and inhibits its activity. The aim of his Senior Fellowship is elucidate how and why the receptor is intracellular in only certain cell types and whether its absence is a key molecular change that drives the chronic inflammation responsible for plaque growth.