ESR 6: Contribution of coagulation to clot formation via clustering and signaling of platelet receptors

Host: Universiteit Maastricht, The Netherlands

Supervisory team: Paola van der Meijden, Hugo ten Cate (School for Cardiovascular Diseases, Maastricht University, NL), Jon Gibbins, Chris Jones (University of Reading, UK), Jolan Harsfalvi (University of Budapest, HU)

Project locations: Maastricht University NL (years 1 and 3); University of Reading UK (year 2); University of Budapest HU (spread 3 months)

Joint PhD Degree: Maastricht University and University of Reading

Project Details: The triad of platelet-coagulation-inflammation is a fundamental driving force in cardiovascular disease, but mechanisms and platelet receptors involved are still largely unknown. In this translational project of TAPAS, ESR6 will focus on unravelling the interactions of this triad, in particular how these interfere with the clustering of GPIb and GPVI receptors. A microfluidics assay with varying platelet, coagulation and inflammatory triggers will be employed to assess a ‘thrombotic risk’ in vitro, in parallel with established static assays (year 1, Maastricht University). The impact of platelet receptor inhibition on the ultrastructure of formed clots will be assessed by optical tweezer nanotechnology (University of Budapest). The information on clot/thrombus formation will be used to build a kinetic model of the contributions of the triad components, i.e. platelet-coagulation-inflammation (year 2, University of Reading). In year 3, the most important interactions will be validated for GPIb and GPVI ligands, using blood samples from controls and patients with a risk of thrombosis, such in combination with clinically used antithrombotics (Maastricht University).

Desirable student skills: Biomedicine, Medical biology; wet lab experience

Relevant references: Mackman N, Spronk HMH, Stouffer GA, Ten Cate H. Dual Anticoagulant and Antiplatelet Therapy for Coronary Artery Disease and Peripheral Artery Disease Patients. Arterioscler Thromb Vasc Biol. 2018; 38(4):726-732.

Nagy M, Heemskerk JWM, Swieringa F. Use of microfluidics to assess platelet-based control of coagulation. Platelets 2017; 28: 441-448.

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