The main focus of our lab is to investigate the pathogenesis and treatment of skeletal ciliopathies. Ciliopathies, which affect ~1 in 1000 people and are caused by abnormal formation or function of cilia (microtubular protrusions present on the surface of most cells within the body), include a number of important human diseases such as renal cystic disease, obesity and retinal degeneration. A subset of ciliopathies, such as Jeune, Carpenter and Sensenbrenner syndromes, also feature particular skeletal involvement. Unlike classical ciliopathies, these so-called ‘skeletal ciliopathies’ are typically caused by mutations in genes encoding ciliary trafficking proteins, including core components of intraflagellar transport (IFT) and vesicle transport machinery. 

One of the main interests of our lab is therefore to investigate the mechanisms that regulate ciliary trafficking. We are currently using tandem-affinity purification (TAP) and stable isotope labeling by amino acids in cell culture (SILAC) to identify novel ciliary trafficking proteins, and high-throughput microscopy-based small molecule screens to identify compounds that target ciliary trafficking, and which may be relevant for therapy.

Another active area of research focuses on neural crest cells (NCCs). There is growing evidence that cilia are present on the surface of NCCs and their derivatives, and skeletal ciliopathies may be caused by abnormal NCC development. The hypothesis that we are currently testing is that factors that influence NCC identity or migration may be targeted for treatment of ciliopathies and other NCC-derived defects (including specific tumours). Chemical and genetic screening is undertaken to identify novel genes and Food and Drug Administration (FDA)-approved drugs that influence NCC development in zebrafish embryos, and these factors are tested for their ability to treat skeletal ciliopathies (e.g. craniosynostosis) in model organisms and to inhibit growth of NCC-derived tumour cell lines.