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Contenido archivado el 2024-05-30

Molecular dissection of inflammatory pathways

Objetivo

Inflammatory diseases are highly prevalent, often chronic diseases that cause diminished quality of life and are connected with major causes of death in Western societies. Despite their societal impact, their pathomechanism is incompletely understood, hindering development of novel therapeutic strategies. In particular, little is known about the intracellular signal transduction processes involved in the tissue destruction phase of aggressive autoimmune diseases such as rheumatoid arthritis. The present proposal aims to clarify this issue using in vivo and in vitro studies on genetically manipulated mice. During the proposed studies, mice deficient in various signal transduction molecules such as Syk, PLCg2, Gab2 and p190 RhoGAPs will be used to test their contribution to inflammatory responses. In vitro studies will test the activation of major effector cells of inflammation (neutrophils, macrophages and osteoclasts) while in vivo studies will utilize mouse models such as autoantibody- and cytokine-induced inflammatory arthritis or autoantibody-induced glomerulonephritis. Further studies will be performed to test the contribution of the above signaling molecules to disease pathogenesis in a lineage-restricted manner, using the Cre-lox approach. Finally, wild type and mutant versions of the signaling molecules tested will be retrovirally re-expressed into the relevant knockout hematopoietic stem cells in vivo to allow structure-function studies during in vivo inflammation. Two novel transgenic strains and a knock-in (floxed) mutant will also be generated during the course of the project. Using state-of-the-art approaches and techniques, this project will provide information at unprecedented molecular detail on signal transduction mechanisms involved in inflammatory diseases, and is expected to point to possible future targets of novel anti-inflammatory therapies.

Convocatoria de propuestas

ERC-2007-StG
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Régimen de financiación

ERC-SG - ERC Starting Grant

Institución de acogida

SEMMELWEIS EGYETEM
Aportación de la UE
€ 1 200 000,00
Dirección
ULLOI UTCA 26
1085 Budapest
Hungría

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Región
Közép-Magyarország Budapest Budapest
Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Irén Baumgartnerné Holló (Ms.)
Investigador principal
Attila Mocsai (Dr.)
Enlaces
Coste total
Sin datos

Beneficiarios (1)