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INVESTIGERFE SIGNED

Investigating the regulation of iron homeostasis by erythroferrone and therapeutic applications

Total Cost €

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EC-Contrib. €

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Partnership

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 INVESTIGERFE project word cloud

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anemias    agonist    pathologies    stores    contribution    mechanism    receptor    erythroferrone    confirmed    synthesis    models    biomedical    suppressed    cells    erythroid    envision    regulatory    abortus    rheumatoid    sought    prerequisite    benefits    arthritis    cancer    regulators    release    chronic    proof    independent    thalassemic    suppresses    anemia    antagonization    showed    regulator    existence    homeostasis    treatment    frequent    leads    therapy    restricted    treatments    axes    examine    identification    ineffective    red    tremendous    first    overload    infections    disorders    recovery    search    thalassemias    therapies    mice    advantage    erfe    absorption    molecules    bowel    hormone    1950s    inflammatory    iron    assay    beta    meet    thalassemia    delineating    human    kidney    blood    mouse    model    opened    levels    action    antagonist    triggered    erythron    loading    disease    murine    signaling    hepcidin    intensifies    manipulation    secondary   

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
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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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