Objective
Multinucleated Giant Cells (MNGCs) arise from the fusion of myeloid cells and are subclassified into osteoclasts, foreign body giant cells, and Langhans giant cells. While osteoclasts are well-characterized in bone physiology, the biology of inflammation-induced MNGCs remains poorly understood. Recent findings from the Lambrecht lab identified an IRF4-dependent transcriptional program in alveolar macrophages (AMs) that drives their fusion into MNGCs in a murine model of IL-33-induced eosinophilic airway inflammation. To dissect these processes, the lab developed the SPAM-deleter model, allowing timed depletion and reconstitution of AMs for precise in vivo analysis of MNGC formation. Additionally, lipid nanoparticle–mediated guide RNA delivery enables rapid CRISPR-Cas9 gene editing in primary AMs in vivo and ex vivo, thus eliminating the need for new mouse lines. These innovative tools create an unprecedented opportunity to uncover the cellular and molecular mechanisms driving inflammatory MNGC formation and function.
I hypothesize that during inflammation, AMs fuse into MNGCs in an osteoclast-like manner, modulate lung tissue function, and later dissociate into individual AMs to repopulate the niche upon resolution of inflammation.
To test this, I will:
- Identify the molecular and cellular drivers of lung MNGC fusion
- Determine the fate of MNGCs after resolution of inflammation
- Define the functional role of MNGCs in chronic lung inflammation
This project will generate novel resources for MNGC research including their transcriptional profile and a MNGC deficient mouse model. While centered on MNGC formation and fate, this project ultimately aims to determine how MNGCs contribute to chronic lung inflammation and how their formation can be therapeutically modulated. By identifying key mechanisms and players, this work will lay the foundation for future strategies to target MNGCs in inflammatory lung disease.
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.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences basic medicine physiology
- natural sciences biological sciences genetics RNA
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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)
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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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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
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(opens in new window) HORIZON-MSCA-2025-PF
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9052 ZWIJNAARDE - GENT
Belgium
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.