The impact of the microenvironment on atherosclerotic plaque stability

Summary

Acute rupture or erosion of atherosclerotic lesions cause heart attack and stroke, which is the major causes of mortality and morbidity worldwide. Whereas many of the processes involved in atherosclerotic lesion formation are known, their destabilisation remains incompletely understood.

We and others have shown that cells derived from pre-existing vascular smooth muscle cells generate the fibrous cap, which provides structural integrity to lesions. However, the cellular plasticity and behaviour of these cell is heavily influenced by other cell types and the microenvironment in the plaque.

Project aims

This project will investigate the relationship between vascular smooth muscle cell regulation and plaque inflammation using patient material obtained from carotid endarterectomy of plaques with high versus low signal in clinical imaging.

Spatial and single cell transcriptomics datasets will be subjected to computational analysis in order to identify molecular mechanisms and cellular interactions that contribute to plaque stabilisation.

CRISPR screening will be used to select candidate factors that will be functionally tested in culture and genetic disease models. Ultimately, this multi-disciplinary approach will link clinical imaging with molecular pathways, in order to pinpoint attractive targets for therapeutic intervention in cardiovascular disease.

This collaborative project will be co-supervised by Dr Jason Tarkin (clinical imaging) and Dr Meritxell Nus (immune cell biology) and will provide opportunities for training in computational analysis of single cell RNA sequencing datasets, preclinical models and molecular techniques. 

Contact details

Dr Helle Jorgensen - hfj22@cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

• PhD