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. Fields of science medical and health sciencesclinical medicinerheumatologymedical and health sciencesclinical medicinegastroenterologyinflammatory bowel diseasemedical and health sciencesbasic medicinepathologymedical and health sciencesclinical medicinehematologymedical and health sciencesbasic medicinephysiologyhomeostasismedical and health sciencesclinical medicinenephrologykidney diseases Keywords iron anemia erythropoiesis Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-STG - ERC Starting Grant Call for proposal ERC-2016-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Net EU contribution € 1 499 235,00 Address RUE DE TOLBIAC 101 75654 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 235,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France Net EU contribution € 1 499 235,00 Address RUE DE TOLBIAC 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 235,00