c-REL transcriptional programmes driving atherosclerosis (Ms Priscila Hirschfeld)

Atherosclerosis, a disease leading to angina, heart attack or stroke, is initiated at regions of arteries that are exposed to disturbed blood flow, which generates low wall shear stress (WSS) at the lumen.

Low WSS induces excessive endothelial cell (EC) proliferation which drives disease by enhancing leakiness to cholesterol-rich lipoproteins.

Classical members of the NF-kB family such as RelA play well-recognized roles in vascular biology, whereas the c-REL NF-kB subunit has not been studied in this context and represents a valuable resource in terms of potential drug targets.Our pilot data reveal that c-REL is strongly induced by low WSS at atheroprone sites and that it induces EC proliferation and promotes atherosclerosis.

The proposed PhD Studentship will integrate hypothesis-led approaches with unbiased transcriptome profiling and murine models to define the mechanisms of c-REL-driven EC proliferation.

The study will generate fundamental information on the biology of c-REL in EC and will identify downstream components of the c-REL pathway that could be targeted therapeutically to prevent or treat atherosclerosis.