Project description
Immune mechanisms of therapeutic resistance in Crohn’s disease
Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal tract, affecting millions of people worldwide and imposing a significant physical, emotional and economic burden. Current therapies, such as TNF-blockade, aim to suppress inflammation, but many patients fail to respond. The EU-funded CD-ResOMics project will investigate how immune regulation contributes to primary therapy failure. Researchers will analyse gene expression profiles of single cells from intestinal biopsies of treatment responders and non-responders over time. Paired blood samples will identify potential biomarkers for patient stratification. The study will reveal the cellular and molecular bases of resistance, guiding improved therapeutic strategies for Crohn’s disease.
Objective
Crohn´s Disease (CD) is a chronic inflammatory disease that affects the gastrointestinal tract, affecting millions of people worldwide and presenting a considerable economic burden to health systems. CD has a serious impact in quality of life, not just physically, but also emotionally and socially. Pathogenesis results from a complex interaction between environmental factors, microbiome, genome, and inflammatory system, leading to disruption of the intestinal mucosa. The imbalance between inflammatory and regulatory cells in maintaining an active disease is well known, and most therapies aim to stop the cascade of inflammatory and pro-inflammatory cytokines (i.e. TNF-blockade). One of the major challenges for treatment is the fact that not all patients respond to therapy. Moreover, the mechanisms behind resistance are still not completely understood, making it hard to correctly stratify patients as responders and non-responders at time of diagnosis. We aim to elucidate changes in immune regulation that explain primary response failure to TNF-blockade in CD. We hypothesise that dysfunction of regulatory cells may prevent reinstatement of homeostasis following inflammation targeting. We will establish single-cell transcriptomics of immune cells from biopsies at the time of diagnosis, as well as in patients responding to treatment and non-responders. Then, we will use computational methods to investigate how immune cells change with time, acquiring a state supporting therapeutic resistance. Moreover, we will illuminate the relationship between immune dysregulation and anatomic niches using spatial transcriptomics. Finally, we will analyse paired peripheral blood samples, for the identification of putative biomarkers for stratification of patients according to TNF-blockade response.
This proposal will provide unprecedented insights on the mechanisms involved in therapeutic resistance in CD, which could potentially lead to the development of new treatment approaches.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.4.1 - Widening participation and spreading excellence
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-WIDERA-2023-TALENTS-02
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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.
1649-035 LISBOA
Portugal
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.