HUMAN CILIA DISEASE BIOLOGY
Our group’s aims are to understand the proteins responsible for building and maintaining ciliary functions in human health and disease. Our current research focus is on how different clinical outcomes for ciliopathy patients arise from different genetic mutations and on translating our lab research to the bedside by development of new genetic-based therapies.
- Genetic diagnostics for PCD, ciliary chondrodysplasias (Jeune Asphyxiating Thoracic Dystrophy) and related sensory ciliopathies. In collaboration with the PCD National Service centres, we are working to develop state-of-the-art diagnostics services for ciliopathies. With the North Thames Regional Genetics Service we have developed a diagnostic ciliopathy gene panel testing service. This ‘Ciliome’, was awarded UKGTN clinical accreditation for delivery nationally. http://www.labs.gosh.nhs.uk/laboratory-services/genetics/molecular-genet...
- Understanding how ciliopathy genotype influences the underlying clinical symptoms and disease lifecourse. From these arising genetic advances we are working to develop a better understanding of how genetics influences the clinical outcomes for ciliopathy patients, and this is already leading to advances in prognostic predictions and improved counselling for affected individuals and their families.
- Gene discovery and functional biology of PCD and Jeune Asphyxiating Thoracic Dystrophy. We are using next-generation sequencing and other omic techniques to identify novel causes of ciliopathy diseases in patients that cannot be diagnosed using the current gene panels. In parallel we are investigating the known disease causes to look at the protein networks that regulate the structure and functions of cilia. For PCD we are focused on the dynein arm assembly process using biochemical and proteomic approaches.
- Novel therapies for PCD and Jeune Asphyxiating Thoracic Dystrophy. We are currently developing in vivo models of PCD and Jeune Asphyxiating Thoracic Dystrophy. We have several projects funded for development of novel genetically targeted ciliotherapies. Together with Chris O'Callaghan and Stephen Hart at UCL GOS-ICH, our groups are targeting therapies at a particularly prevalent mutational types causing PCD.
- Retinal and neurological defects underlying juvenile Batten disease. In collaboration with Clare Futter (UCL IoO) we are working to understand the basis of retinal and neuronal degeneration in juvenile Batten disease using the Cln3Δex1-6 knockout model.