Neurodevelopmental disorders (i.e. intellectual disability, autism) affect >1% of the population, and often have a genetic basis. Our lab seeks to get insight in the molecular and cellular mechanisms underlying these disorders, with the ultimate goal to develop treatments. Our research into these disorders is divided into three research lines: (1) Improving genetic diagnosis, (2) Understanding the mechanisms underlying neurodevelopmental disorders (3) Translational studies (i.e. clinical trials) to improve the quality of life of the affected individuals.
To improve genetic diagnosis, we have developed together with van Woerden lab a functional genomics screen (PRiSM) to rapidly determine if a genetic variant is pathogenic. This screen is not only important for providing a diagnosis, but also allows us to get more insight in the genes underlying neurodevelopment.
Understanding the mechanisms underlying neurodevelopmental disorders
To get more insight in the pathophysiology of neurodevelopmental disorders, we typically make use of genetically engineered mouse models as a tool to dissect the underlying mechanisms. Mouse models are analyzed at the biochemical, cellular (electrophysiological) and behavioral level. By analyzing the mice at all these levels we hope to understand the specific function of these genes and proteins in brain development and learning and memory. Besides mouse models, we are currently also exploring the value of iPS cells to study these disorders. The genes and proteins that we specifically focus on are proteins associated with the RAS-ERK-MTOR signaling pathway and the proteasome.
To translate our findings to the patients, we are part of the ENCORE expertise center for neurodevelopmental disorders, for which Ype Elgersma is the scientific director. ENCORE has large expertise outpatient clinic for Angelman Syndrome, Neurofibromatosis (NF1), Tuberous Sclerosis (TSC), Fragile X and genetic forms of autism.