Objective
Macrophages exist in distinct differentiation states. Proangiogenic/immunosuppressive (M2-like) macrophages and antitumoral/proinflammatory (M1-like) macrophages represent two extremities of a continuum. Because lineage-defined subsets have not been identified yet, macrophage heterogeneity is likely to reflect the plasticity of these cells in response to microenvironmental signals. The concept that hypoxia can induce inflammation has gained general acceptance. However, little is known on how extravasated monocytes and their macrophage progeny react to a condition of low oxygen. Different macrophage phenotypes have been positively and negatively associated with the clinical outcome of vascular disorders as cancer and ischemia. These pathological conditions are characterized not only by dysfunctional vessels, which impair oxygenation, but also by strong immunoregulatory responses. Recently we have shown that reduced activity of the oxygen sensor PHD2 in macrophages skews their polarization towards a proarteriogenic (M2-like) phenotype, which confers protection against ischemia. Based on these findings, we propose to dissect upstream and downstream signals to the oxygen sensing machinery and hypoxia-response in macrophages. By using a genome-wide transcriptional profiling approach and a high-throughput interactome analysis, combined with mouse genetic tools, we will identify the gene signature of macrophages in hypoxia and unravel the molecular executors of this response. The identification of the effectors responsible for macrophage skewing in relation to oxygen availability will contribute to a better understanding of immunoregulatory cues during disease progression and unveil the multifaceted function of macrophages during vessel formation. With the focus of our research on macrophage manipulation towards a desired phenotype, we will offer new treatment options for cancer and ischemia that might result in optimized therapies and overcome resistance to current drugs.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- medical and health sciences clinical medicine oncology
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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.
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.
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.
ERC-2012-StG_20111109
See other projects for this call
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.
Host institution
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.