Steroid receptor and epigenetic co-regulator function in tissue homeostasis

Androgens increase muscle mass, but their therapeutic efficacy in sarcopenia is limited due to their effects on prostate cells. Conversely, long-term treatments with anti-androgens have numerous side effects, including muscle wasting. The latter is also observed with glucocorticoid treatments (e.g. prednisone, dexamethasone), the most commonly prescribed drugs for chronic inflammatory disorders, such as asthma and arthritis. Interestingly, androgen and glucocorticoid receptors recognize similar DNA sequences.

Our project aims to understand the mechanisms underlying the action of these hormones to reduce their side effects on skeletal muscles via two approaches: (i) identifying the molecular determinants that confer androgen- and glucocorticoid- tissue specificity, and (ii) modulating the activity of epigenetic coregulators, including the histone demethylase Lsd1.