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Interplay of epithelial mechanics and neutrophil activation as a pathomechanism in refractory IBD and colorectal cancer patients

Objective

Inflammatory bowel diseases (IBD) are a heterogeneous group of disorders characterized by gastrointestinal tract inflammation, being Crohn's Disease and Ulcerative Colitis, the most clinically abundant. IBD affects around 6.8 million people all over the world, being Europe the continent with the highest prevalence. Although anti-TNF-α monoclonal antibodies are a breakthrough therapy, almost 40% of IBD patients do not respond to therapy or acquire resistance. This leads to uncontrolled inflammation that, prolonged in time, constitutes a higher Colorectal Cancer risk. This justifies the current efforts to identify innovative therapy targets for IBD understanding of the molecular processes behind (personalized medicine). The fact that an increased intestinal permeability precedes the onset of inflammation possesses epithelial disruption as a potential etiological factor in IBD. Moreover, in recent years, several publications have highlighted that an impaired epithelial barrier is linked to resistance to therapy. Nevertheless, how altered epithelial mechanics can influence the structural properties of the extracellular matrix and immune cells migrating through it is not fully understood. On the other hand, the role of neutrophils as resistance-to-therapy players has emerged very recently. Then, we hypothesize that an alteration in epithelial cell mechanics constitutes a primary event that impacts the proliferation and behavior of the first immune cell responders: neutrophils. This would further contribute to ECM remodeling and fibroblasts polarization to IAFs (another mechanism implicated in therapy resistance). Then, INTERCONNECTIONS aims to elucidate how an altered epithelial dynamics constitutes a primary event that directly (through an altered transepithelial migration) or indirectly (affecting the mechanical framework) could promote the accumulation of activated neutrophils.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

UNIVERSITATSKLINIKUM ERLANGEN
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.

€ 173 847,36
Address
MAXIMILIANSPLATZ 2
91054 ERLANGEN
Germany

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Region
Bayern Mittelfranken Erlangen, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

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