About this research groupThis research group includes research that identificates genes that are disrupted in neurodevelopmental disorders. It also studies mechanisms of disease, epigenetic mechanisms and gene regulatory pathways, and develops therapeutic interventions for Kleefstra syndrome and Myotonic Dystrophy. read more (DCMN)
AimsHans van Bokhoven is a full professor and head of the Molecular Neurogenetics unit. The focus of his research is on neurodevelopmental disorders, in particular intellectual disability (ID), autism (ASD), neural migration disorders and other cognitive disorders. Over the years, his research has identified a large number of genes (around 100) that carry causative mutations in a variety of (neuro)developmental disorders that have an important medical and socio-economical impact to our society. This work has generated many new opportunities for diagnostics, counseling and clinical management of patients with cognitive disorders. His recent research elaborates on the notion that the overlapping comorbidities seen amongst different neurodevelopmental and psychiatric disorders have a common molecular basis. He has been a pioneering advocate of this concept of converging networks and pathways amongst neurodevelopmental disorders, such as synaptic activity and chromatin disruptions. These common mechanisms provide an excellent starting point for fundamental research and research aimed to develop new strategies for intervention. To that end, we follow a multi-level strategy that, besides neurogenetics, includes functional analyses of in vitro and in vivo models. In vivo studies comprise neurobiological and behavioral research in animal models, in particular Drosophila melanogaster (fruit flies) and mice. In vitro studies encompass the manipulation and neurophysiological assessment of primary neurons from wildtype and mutant rodent model organisms. In addition, we have established a core group for the generation of induced pluripotent stem cells, which we use to generate neural lineages for functional studies and for pre-clinical testing of pharmaceutical interventions.
DiscoveriesSome discoveries are found below.
Identification of novel disease genes for human disorders.
IdentificationIdentification of many (>100) novel “disease genes” for human disorders. Prominent examples of disorders explained by Hans's research include EEC syndrome (TP63), Robinow syndrome (ROR2), Feingold syndrome (MYCN), Kleefstra syndrome (EHMT1), Walker-Warburg syndrome (Dystroglycanopathy genes), Möbius syndrome, and many genes for Intellectual Disability (ID).
Leading in highlighting the importance of epigenetic regulator genes in the occurrence of neurodevelopmental disorders.
Epigenetic regulator genesThe notion that ID genes converge to common biological pathways, which formed the basis of his inaugural lecture “Networks in the Brain”. Hans was one of the first to highlight the importance of epigenetic regulator genes in the occurrence of intellectual disability, autism, and other neurodevelopmental disorders.
We have set up a pipeline for generating and functional analysis of patient-derived neural cell lineages.
PipelineWe have set up a pipeline for generating and functional analysis of patient-derived neural cell lineages. Proof-of-concept was established by establishing excitatory neurons, starting from fibroblasts from patients with Kleefstra syndrome caused by mutation of the EHMT1 gene. These patient-derived neurons exhibit synaptic defects that mimic those of corresponding mouse models. In addition, culturing of these neurons on multi-electrode arrays dishes revealed gene-specific neural network anomalies. These aberrant network activities are currently used to screen chemical compound libraries to identify drugs can restore the defect, which has already revealed potential lead compounds for further inverstigation in animal models.