Rett syndrome is a rare neurodevelopmental disorder where treatment is purely symptomatic with no curative treatment. The paucity of any disease-modifying therapeutics entering the clinic is primarily due to the lack of useful clinical biomarkers and a complete understanding of the complex underlying disease pathophysiology and function of MeCP2. Recently, the application of high-throughput approaches known as “omics” has developed rapidly and revolutionised the diagnosis and the understanding of the pathophysiology of many neurological disorders. Additionally, cortical brain organoids are an emerging human 3D model that mimics various developmental features at the cellular and molecular levels and provides a powerful model for studying neurodevelopmental disorders. 

By harnessing the power of omics platforms along with advanced stem cell technology, my project aims to dissect the molecular complexity of Rett syndrome to identify genes, proteins, metabolites, and cellular pathways from the blood that are differentially dysregulated among patients in the cohort (relative to controls) in an unbiased approach. This integrated approach will identify the dysregulated pathways in Rett syndrome individuals, providing an impartial approach to therapeutic targets that will lead to preclinical validation, the initiation of transformative Phase I clinical trials and the translation of novel therapeutics from clinical trials into clinical care.