ProjectCH 1541/2-1 – Regulatory molecular mechanisms governing immunothrombotic adversities in heparin-induced…

Basic data

Acronym:
CH 1541/2-1
Title:
Regulatory molecular mechanisms governing immunothrombotic adversities in heparin-induced thrombocytopenia: validation of novel therapeutic strategies
Duration:
01/01/2025 to 31/12/2027
Abstract / short description:
Platelet express the noncanonical G-protein coupled chemokine receptor CXCR7. Recently we have validated the potential of CXCR7 as an anti-thrombotic mediator in arterial thrombosis, and following myocardial infarction through a profound modulation of the platelet lipidome that consequently substantiates platelet inhibitory signalling through the cAMP-PKA pathway. The proposed project, aims to disclose the molecular mediators of thrombo-inflammation in HIT with a particular focus on the therapeutic validation of the CXCR7-cAMP axis. The main research objectives of the proposed project are: I. To investigate the therapeutic potential of targeting CXCR7 in HIT-induced platelet-mediated thrombo-inflammatory functions (in vitro and ex vivo studies) in conjunction with neutrophils II. To explore the molecular mechanisms (through phosphoproteomics, lipidomics evaluation in response to HIT-monoclonal antibody triggered FcγRIIA mediated platelet activation) governing enhanced thrombotic risk in HIT. Translational perspective will focus on delineating the regulatory effect of the CXCR7-cAMP axis (in vitro. ex vivo) to combat thrombotic disposition in HIT patients. III. Preclinical evaluation of the use of pharmacological CXCR7-agonist compared to antiplatelet therapy iloprost as a therapeutic strategy to regulate immunothrombotic complications in HIT (in vivo studies with murine models). IV. To analyse possible changes in CXCR7 expression in HIT patients as a potential novel drug target on platelets and neutrophils (clinical study) and ascertain its anti-thromboinflammatory efficacy in ex vivo studies. If the results of this study show the anticipated outcome, planning for prospective clinical studies to assess the use of CXCR7 agonist as a new treatment of HIT will be initiated. In addition, the expression of CXCR7 will be implemented in the routine diagnostic approach for HIT to supplement other laboratory assays.

Involved staff

Managers

Faculty of Medicine
University of Tübingen
Research training group: Non-canonical G protein signaling pathways
Research training groups

Contact persons

Institute for Clinical and Experimental Transfusion Medicine
Hospitals and clinical institutes, Faculty of Medicine

Local organizational units

Institute for Clinical and Experimental Transfusion Medicine
Hospitals and clinical institutes
Faculty of Medicine

Funders

Bonn, Nordrhein-Westfalen, Germany
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