Novel Therapeutic Routes via X Chromsome Reactivation.

We aim to discover novel therapeutic routes for X-linked diseases through XCR investigation. Although apparently homogenous, the inactive X chromosome (Xi) has a highly heterogenous chromatin with distinct domains characterised by different histone modifications (e.g. H3K27me3 and H3K9me3) and deposited by different chromatin modifying enzymes (e.g. PRC2, HP1, SmchD1 and TRIM28). This creates a combinatorial code that tunes X chromosome inactivation differently along the chromosome. We, therefore, aim to screen for epi-drugs and/or chromatin remodelling factors that are able to reactivate specific portions of the Xi chromosome. This will allow us to develop new therapies for those X linked-diseases such as neurodevelopmental (Rett syndrome) and neuromuscular diseases, and might be applied to sex-biased diseases.

This project is funded by an AFM telethon grant.