Glucocorticoids are the most prescribed compounds for inflammatory diseases, including asthma and arthritis. However, long-term treatments are limited by adverse effects, such as diabetes and muscle wasting. Glucocorticoids effects are mediated by the glucocorticoids receptor (GR), a member of the ligand-dependent nuclear receptor superfamily. Recent data obtained in the lab show that levels of the histone demethylase Lsd1 increase upon glucocorticoid-induced muscle wasting, and that Lsd1 interacts with GR in skeletal muscle, indicating that Lsd1 acts as a coactivator of GR to promote muscle catabolism. In line with this hypothesis, we found that myofiber Lsd1 is required for the induction of proteolysis-related genes upon starvation. Therefore, the current project aims at determining whether GR activity can be modulated by targeting its tissue-specific co-regulators. The fellow’s tasks will be to identify the role of Lsd1 in muscle fibers in basal conditions and in glucocorticoid-induced muscle atrophy, and to determine whether an Lsd1 inhibitor can reduce muscle wasting. He/she will also characterize the associated epigenetic landscape using cutting-edge technics. Our team has recently developed several projects based on genome-wide characterization of transcription factor cistromes and transcriptomes in various tissues of genetically modified mice, thereby providing the unique opportunity to decipher the in vivo mode of action of nuclear receptors. Overall, this study should clarify the role of Lsd1 in muscle fibers and open new avenues to counteract glucocorticoid-induced side effects.