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Platelet Endothelial Aggregation Receptor 1

Project description

New insight into blood clotting: implications for thrombosis treatment?

Cardiovascular disease, the leading cause of death worldwide, often leads to myocardial infarction and ischemic stroke due to occlusive thrombus formation. Blood clotting is a complex process that involves many different cell types and factors. Scientists of the EU-funded PAELLA project propose to study the role of the newly identified platelet receptor PEAR1 on haemostasis, inflammation and thrombosis. Through state-of-the-art methodologies, they will activate the receptor and study its impact on platelets, testing the hypothesis that PEAR1 drives thrombo-inflammatory disease in the vasculature. The work will unveil novel aspects in the blood clotting process and may lead to new treatment strategies to combat thrombosis.

Objective

Cardiovascular disease is the leading cause of death world-wide, affecting both men and women. Myocardial infarction and ischemic stroke are two severe consequences of cardiovascular disease caused by formation of an occlusive thrombus. Blood coagulation and thrombus formation is a complex interplay between clotting factors, platelets and endothelial cells lining the blood vessels that often involve interactions with leukocytes and other inflammatory cells. I propose to study a novel receptor on platelets, PEAR1, and its role in haemostasis, inflammation and thrombosis. I will use unique, synthetic poly-sulfated sugars that I have characterised as novel agents to activate PEAR1 and take advantage of the 30 years of experience of my host, Professor Watson, in studying platelet activation, and the recent identification (unpublished) of the natural ligand in the body which activates PEAR1. I will use state-of-the-art methodology available in Birmingham including flow chamber studies, CRISPR-CAS knock-down, phosphoproteomics, super-resolution and light sheet microscopy, intravital microscopy and a PEAR1 deficient mouse model to test my hypotheses that PEAR1 plays a critical role in thrombus stabilisation at sites of injury and drives thrombo-inflammatory disease in the vasculature. Uncovering the role of the novel receptor PEAR1 may lead to new treatment strategies to combat thrombosis.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

THE UNIVERSITY OF BIRMINGHAM
Net EU contribution
€ 212 933,76
Address
Edgbaston
B15 2TT Birmingham
United Kingdom
Region
West Midlands (England) West Midlands Birmingham
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 212 933,76