Project description
New molecular targets against lung fibrosis
Idiopathic pulmonary fibrosis (IPF) is a lung disease associated with the formation of scar tissue, which leads to a gradual decline in lung function. Available drugs slow but do not stop disease progression, and lung transplantation is the only curative option. Recent findings suggest that monocyte-derived macrophages (MDMs) drive lung scarring by activating fibrotic processes. With the support of the Marie Skłodowska-Curie Actions programme, the IPF-MDM-GREMLIN project will investigate whether targeting the protein GREM1 can halt pulmonary fibrosis through its actions on MDMs. GREM1 is expressed in MDMs, and researchers will study its role in patient-derived cells and animal models.
Objective
The problem: Idiopathic pulmonary fibrosis (IPF) is a rare, progressive lung disease resulting in respiratory failure. IPF is irreversible and patient’s median survival is 3-5 years post-diagnosis. The only curative recourse is lung transplantation because nintedanib and pirfenidone, the only two treatment options slow disease progress but do not cure or cause disease regression. Specific depletion of profibrotic monocyte-derived macrophages (MDMs) protects mice against pulmonary fibrosis suggesting a causal role for MDMs in disease development. While these depletion approaches can be undertaken experimentally, they cannot be performed in humans because MDMs are required for normal immunity. Thus, a targeted blockade of the mechanisms causing excessive profibrotic activation of MDMs is required to develop novel therapeutic approaches.
The discovery: My proposal arises from the Host's recent finding that depletion of the bone morphogenetic protein antagonist GREM1 in mouse MDMs inhibits their profibrotic activation.
The proposal: My proposed work will determine whether targeted deletion of GREM1 in human MDMs inhibits their profibrotic activation and prevents pulmonary fibrosis in an animal model.
The objectives: To evaluate the above, I have identified two specific objectives (SO):
SO1. Determine the precise roles of endogenous and exogenous GREM1 in regulating the profibrotic activation of MDMs derived from IPF patients and healthy controls
SO2. Determine whether GREM1 deletion in MDMs protects against pulmonary fibrosis in an animal model
The outcomes: I will determine the role of MDM-derived GREM1 in pulmonary fibrosis potentially identifying a new therapeutic approach. I will receive critical training in a world-class institution, allowing my research to span clinical and pre-clinical studies to in-vivo imaging and omics techniques. The scientific and transferable skills I will obtain are essential for a successful academic or non-academic career.
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.
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.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine transplantation
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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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-MSCA-2024-PF-01
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4 Dublin
Ireland
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