TameThiflam
Financiado
Targeting mechanisms of Thrombo-inflammation
The recent Covid-19 pandemic dramatically illustrated (i) the clinical relevance of thrombo-inflammation (the interplay of coagulation and inflammation) and (ii) our limited understanding of molecular mechanisms of thrombo-inflamm...
The recent Covid-19 pandemic dramatically illustrated (i) the clinical relevance of thrombo-inflammation (the interplay of coagulation and inflammation) and (ii) our limited understanding of molecular mechanisms of thrombo-inflammation. Thrombo-inflammation is a frequent disease-driving mechanism, impairing out-come of viral or bacterial infection, cardiovascular disease, cancer and other diseases. The lack of mechanistic insights hampered the development of specific therapies. My group recently discovered a new molecular link between coagulation and inflammation that addresses this enormous unmet medical need: the initiator of coagulation, tissue factor (TF, F3, CD142), forms a previously unknown heterodimer with the cytokine receptor IFNAR1 (Interferon-alpha/beta receptor alpha chain) on resting cells. In this heterodimer, TF and IFNAR1 are both inactive. Upon stimulation (e.g. fVII/fVIIa, LPS, polyIC) the heterodimer dissociates, activating TF-mediated coagulation, IFNAR1-mediated inflammation, and cellular metabolism. This provides a novel, yet simple molecular switch simultaneously controlling coagulation, inflammation, and metabolism. This “switch” is expected to provide a new conceptional framework for thrombo-inflammatory diseases. To enable future translation of this novel mechanism, I aim to address the following open questions (i) how is this molecular switch regulated in an organ and context specific fashion (in vitro work; cell-specific inducible TF±IFNAR1 deficient mice)? (ii) what are the consequences of this molecular switch for intracellular signaling, inflammation, mitochondrial metabolism (omics with bioinformatic analyses)? and (iii) what are the molecular structures required for the TF-IFNAR1 interaction (cross-linking, crystallography, phage display, computational modeling)? I expect that answering these questions will lead to new diagnostic and therapeutic approaches revolutionizing the way we detect and treat thrombo-inflammatory diseases.
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Duración del proyecto: 59 meses
Fecha Inicio: 2024-11-01
Fecha Fin: 2029-10-31
Fecha Fin: 2029-10-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-11-01
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2023-ADG:
ERC ADVANCED GRANTS
Cerrada
hace 1 año
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
UNIVERSITAET LEIPZIG
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5