We conduct cutting-edge cardiovascular research.
Our research focuses on the biomechanical mechanisms that control atherosclerosis, a disease of arteries that can lead to angina, heart attack and stroke. Disturbed blood flow generates frictional forces (shear stress) that trigger pathophysiological changes in endothelial cells that promote atherosclerosis initiation and the progression of plaques into dangerous unstable forms prone to rupture or erosion.
Computational fluid dynamic (CFD) simulation of the blood flow patterns in a normal carotid artery bifurcation. Movie kindly provided by Professor David Steinman (lab webiste: https://bsl.mie.utoronto.ca/)
The laboratory combines genomics approaches with unbiased functional screening and biochemical studies to identify the signaling pathways and transcriptional programs that regulate endothelial cell responses to flow. The goal is to identify molecules within these pathways that can be targeted to prevent or treat atherosclerosis.
The cross-disciplinary nature of our work has led to interactions with physicist and engineers as well as molecular and cellular biologists and clinical scientists.
Staining of RelA and VCAM-1 in the murine aorta
(Circ Res 2011;108:950-959).
TWIST1 expression is enriched at a low shear stress region of the aorta (Mahmoud et al. Circ Res. 2016 119: 450-462).
Model of integrin structural changes in response to mechanical force
(Xanthis et al J Cell Sci 2019;132;jcs229542).
Current Projects (current funding >£2M).
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MRC Project Grant: "Role of the transcription factor GATA4 in atherosclerosis progression" 2021-2024
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BHF Programme Grant: “Role of the transcription factor TWIST1 in endothelial pathophysiology and atherosclerosis progression”. 2020-2025
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BHF Intermediate Basic Science Fellowship: “Role of the mechanoreceptor Pkd1 in endothelial dysfunction and atherosclerosis”. Awarded to Dr Jovana Serbanovic-Canic.
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BHF PhD Studentship: “c-REL transcriptional programmes driving atherosclerosis”. 2020-2023
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A* STAR PhD: "Role of the transcription factor TWIST1 in stroke”. 2021-2024"