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INVESTIGERFE SIGNED

Investigating the regulation of iron homeostasis by erythroferrone and therapeutic applications

Total Cost €

EC-Contrib. €

Partnership

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INVESTIGERFE project word cloud

Explore the words cloud of the INVESTIGERFE project. It provides you a very rough idea of what is the project "INVESTIGERFE" about.

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

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. telephone: n.a. 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 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. telephone: n.a. fax: n.a.	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

List of publications.
year	authors and title	journal	last update
2019	Sabrina Bondu, Anne-Sophie Alary, Carine LefÃ¨vre, Alexandre Houy, Grace Jung, Thibaud Lefebvre, David Rombaut, Ismael Boussaid, Abderrahmane Bousta, FranÃ§ois Guillonneau, Prunelle Perrier, Samar Alsafadi, Michel Wassef, RaphaÃ«l 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 BillorÃ©, Maria Rosa Lidonnici, Cavan Bennett, Giacomo Mandelli, Sant-Rayn Pasricha, Giuliana Ferrari, Clara Camaschella, LÃ©on 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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