MSc BY RESEARCH: Can we improve patient outcomes by providing a more personalized approach to antiplatelet therapies?

Heart attacks occur when a blockage called a thrombosis develops in the blood vessels of the heart which is a major cause of morbidity and mortality. Platelets play a central role in the development of arterial thrombosis in heart disease, responding to a variety of extracellular stimuli and agonists to undergo a rapid aggregation response, leading to a rapidly growing thrombus. Central amongst these agonists are TxA2 and ADP which operate through G protein-coupled receptors (GPCRs) on the platelet surface: TP for TxA2 and P2Y1 and P2Y12 for ADP. Current therapeutic strategies for the treatment of arterial thrombosis are largely based on these well characterized receptor systems with aspirin (which reduces TXA2 generation) and P2Y12R antagonists commonly used effective anti-platelet agents with their combination, termed dual antiplatelet therapy (DAPT). Although DAPT offers synergistic benefits in preventing thrombus formation not all patients benefit to the same extent with a marked inter-individual variability in the extent of platelet inhibition. The variability of response to DAPT results in a significant proportion of patients demonstrating either high or low platelet reactivity with an associated risk of thrombotic or bleeding events, respectively. To date, platelet function testing has achieved predominantly negative results in reducing adverse events secondary to DAPT therapy although studies have largely focussed on the entire patient population rather than those at either end of the platelet reactivity spectrum.

1) to characterize platelet receptor biology in coronary intervention patients experiencing high and low platelet reactivity and assess the effectiveness of DAPT on these patients.

2) characterize the usefulness of existing methods to assess the effect of anti-platelet agents on platelet function.

3) develop novel methods of platelet function assessment that may facilitate tailoring of therapy with a reduction in adverse clinical events.

In order to undertake this programme of research you will be supported by an established network of clinical (Bristol Heart Institute) collaborators. This grouping will provide you with both the logistical support and access to patient samples from ongoing clinical trials at the University Hospitals Bristol NHS Foundation Trust. You will receive training in a wide variety of relevant techniques ranging from advanced fluorescent single cell imaging microscopy through to the measurement of cell signalling pathways.

Please do contact me at s.j.mundell@bristol.ac.uk if you would like further information about this exciting opportunity.