ANR HYPOXIA : Betty Gardie (2024 - 2026)

Betty Gardie is the scientific leader of the ANR funded project : Highlighting Novel Mechanisms SwaYing ErythroPOietin EXpressIon and RegulAtion
 

Abstract

Erythropoietin (EPO) is a key hormone regulating red blood cell production, primarily produced by the kidney after birth. We recently identified novel germline mutations in non-coding regions of the EPO gene. These mutations lead to the abnormal expression of hepatic-like EPO (hep-EPO), revealing a new mechanism of disease. Using induced pluripotent stem cells (iPSCs) derived from patients and differentiated into hepatocyte-like cells, we demonstrated EPO overexpression, suggesting the involvement of previously unknown regulatory elements that control hep-EPO expression. Our project aims to identify additional HE patients expressing this EPO isoform, discover new regulatory mutations by sequencing the full EPO gene, investigate the molecular mechanisms of hep-EPO expression using high-throughput genomics, and explore strategies to modulate EPO production through gene editing or targeted drugs. Given EPO’s known protective roles beyond erythropoiesis—including in the cardiovascular, renal, and nervous systems—stimulating hepatic EPO could have major therapeutic potential, particularly for anemic patients with kidney failure, and hep-EPO may also serve as a biomarker of liver disease severity.