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Thrombotic MEMOry-Linking a break in tolerance to platelets to REthrombosis

Project description

Targeting platelet-directed immunity as an anti-thrombotic strategy

Accumulating evidence indicates that thrombosis - the formation of blood clots - leaves systemic traces and is much more than a local event. The EU-funded T-MEMORE project will test a novel concept that venous thromboembolism is a chronic disease caused by an immune response against activated platelets. Researchers will dissect the mechanisms of platelet production and removal in the bone marrow, spleen and liver and determine the profile of patients at risk or with recurrent thrombotic events. Manipulation of platelet-directed immunity will be tested as an alternative to the standard preventative therapy for venous thromboembolism with anticoagulant.

Objective

Thrombotic diseases like venous thromboembolism (VTE) are leading causes of mortality worldwide, due to their unpredictable, relapsing occurrence. The strongest predictor of a thrombotic event is a previous thrombosis, implicating that VTE has systemic memory effects beyond local clot formation triggering thrombotic relapse. In T-MEMORE, I will go beyond the state-of-the art of thrombosis research by testing the ground-breaking concept that VTE is not only a local event, but a chronic, systemic disease caused by an immune response to platelets mimicking a break in tolerance.
My recent research revealed that venous thrombosis is the outcome of a sterile inflammation primarily directed against one target: activated platelets. I found that platelet-directed immunity in turn fosters platelet activation and thrombotic vessel occlusion. The systemic and long-term thrombotic memory effects of platelet-directed immunity are unknown, but have important implications for unmet clinical needs: (1) identification of patients at risk of rethrombosis; (2) personalisation of the duration and type of secondary prevention; (3) discovery of new approaches for VTE prophylaxis beyond anticoagulants with their inherent bleeding risk.
The thrombotic memory effect caused by a local thrombosis will be deciphered by innovative functional in vivo imaging in the bone marrow as the site of platelet production as well as spleen and liver as sites of platelet removal (objective 1). The potential of manipulating platelet-directed immunity to prevent thrombotic relapse will be tested in a clinically relevant model of rethrombosis (objective 2). In a translational approach, I aim to uncover a platelet-directed immune profile in patients with recurrent VTE, which would be a key step towards a personalized, molecular-guided therapy (objective 3). The overarching aim of T-MEMORE is to prove the concept of thrombotic memory as an innovative approach for the targeted prevention of VTE recurrence.

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Topic(s)

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2020-STG

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Host institution

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 483 145,00
Address
GESCHWISTER SCHOLL PLATZ 1
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 483 145,00

Beneficiaries (1)

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