INVESTIGERFE SIGNED
Investigating the regulation of iron homeostasis by erythroferrone and therapeutic applications
Total Cost €
0EC-Contrib. €
0Partnership
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Project "INVESTIGERFE" data sheet
The following table provides information about the project.
| Coordinator |
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Organization address contact info |
| Coordinator Country | France [FR] |
| Total cost | 1˙499˙235 € |
| EC max contribution | 1˙499˙235 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2016-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2017 |
| Duration (year-month-day) | from 2017-05-01 to 2022-04-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE | FR (PARIS) | coordinator | 1˙499˙235.00 |
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Project objective
The existence of an “erythron-related regulator” that intensifies iron absorption and its release from stores to meet the requirements for red blood cells synthesis was proposed in the 1950s. Delineating this mechanism is of high biomedical importance as the pathway could be targeted to develop novel treatments for iron-restricted anemias that are very frequent but for which current therapies are ineffective (e.g. infections, inflammatory bowel disease, cancer, or chronic kidney disease) and for iron-loading anemias (e.g. thalassemias). We have recently identified the hormone erythroferrone (ERFE) and showed that it could be the long-sought erythroid regulator of iron homeostasis. ERFE suppresses the synthesis of the iron-regulatory hormone hepcidin to facilitate the recovery from anemia but leads to secondary iron overload in β-thalassemia. The potential of ERFE in the treatment of iron disorders is tremendous but understanding its mechanism of action is a prerequisite to envision ERFE-based therapies. The identification of ERFE has opened new research areas and our project will be organized around four axes. 1) Develop an assay to measure ERFE levels in human pathologies. Its contribution is not known and needs to be confirmed. 2) Identify the receptor for ERFE, the signaling pathways triggered by ERFE, and molecules with agonist/antagonist effects, a prerequisite in the development of new therapies. 3) Search for potential other erythroid regulators. We will take advantage of the Erfe-/- mice to determine whether hepcidin could be suppressed by an ERFE-independent mechanism. 4) Study the potential of ERFE manipulation in therapy in the mouse. We will first establish a proof of principle in a mouse model of anemia (B. abortus). The benefits of ERFE antagonization will be addressed in thalassemic mice. We will also examine the role of ERFE in murine models of chronic anemia: chronic kidney disease, inflammatory bowel disease, rheumatoid arthritis and infections.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Sabrina Bondu, Anne-Sophie Alary, Carine Lefèvre, Alexandre Houy, Grace Jung, Thibaud Lefebvre, David Rombaut, Ismael Boussaid, Abderrahmane Bousta, François Guillonneau, Prunelle Perrier, Samar Alsafadi, Michel Wassef, Raphaël Margueron, Alice Rousseau, Nathalie Droin, Nicolas Cagnard, Sophie Kaltenbach, Susann Winter, Anne-Sophie Kubasch, Didier Bouscary, Valeria Santini, Andrea Toma, Mathild A variant erythroferrone disrupts iron homeostasis in SF3B1 -mutated myelodysplastic syndrome published pages: eaav5467, ISSN: 1946-6234, DOI: 10.1126/scitranslmed.aav5467 |
Science Translational Medicine 11/500 | 2020-01-30 |
| 2019 |
Irene Artuso, Mariateresa Pettinato, Antonella Nai, Alessia Pagani, Ugo Sardo, Benjamin Billoré, Maria Rosa Lidonnici, Cavan Bennett, Giacomo Mandelli, Sant-Rayn Pasricha, Giuliana Ferrari, Clara Camaschella, Léon Kautz, Laura Silvestri Transient decrease of serum iron after acute erythropoietin treatment contributes to hepcidin inhibition by ERFE in mice published pages: e87-e90, ISSN: 0390-6078, DOI: 10.3324/haematol.2018.199810 |
Haematologica 104/3 | 2020-01-30 |
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