dr. D. Schubert (Dirk)
Universitair docent - Donders Center of Medical Neurosciences
Gastonderzoeker - Donders Institute for Brain, Cognition and Behaviour
Universitair docent - Donders Institute for Brain, Cognition and Behaviour
The scaffold of proper structural and functional organization of the neuronal networks depends on the activity of a multitude of different transcription factors, growth factors and neuromodulators during brain development. Many neurological disorders and their related cortical dysfunctions can be linked with abnormal activity of one or more factors or neuromodulators - be it because of genetic variations or because of pharmacological modulation during critical periods of brain development.
In our group, we currently focus on linking gene to neuronal network function in health and disease. To this end we investigate the structural and functional organization and maturation of the neural networks on two levels and with two translational links:
1: The role of the neuromodulator serotonin on the development of the somatosensory system (rodent model systems).
2: Epigenetic factors and neuronal network formation in models systems ( human induced pluripotent stem cell derived neuronal cultures) for intellectual disability and schizophrenia.
For our research we combine molecular, neuroanatomical, electrophysiological in vitro techniques (from single cell patch clamp over paired recordings to multielectrode array recordings), with optical stimulation (optogenetics), modelling as well as molecular assays, cell culture and behavioural approaches, partially via intense collaborations with other research groups.
- Cadherin-13 is a critical regulator of GABAergic modulation in human stem cell derived neuronal networks. Mossink B, van Rhijn J-R, Shan Wang S,..., Schubert D†, Nadif Kasri†. (2021) Mol Psychiatry (2021). https://doi.org/10.1038/s41380-021-01117-x. †Authors contributed equally to this work Volledige tekst
- Human neuronal networks on micro-electrode arrays are a highly robust tool to study disease-specific genotype-phenotype correlations in vitro. Mossink B, Verboven AHA, van Hugte EJH, Klein Gunnewiek TM, Parodi G, Linda K, Schoenmaker C, Kleefstra T, Kozicz T, van Bokhoven H, Schubert D, Nadif Kasri N, Frega M. (2021) Stem Cell Reports. 2021 Jul 13:S2213-6711(21)00326-X. doi: 10.1016/j.stemcr.2021.07.001. Epub ahead of print. PMID: 34329594. Volledige tekst
- EHMT1 regulates Parvalbumin-positive interneuron development and GABAergic input in sensory cortical areas. Negwer M, Piera K, Hesen R, Lütje L, Aarts L, Schubert D, Nadif Kasri N. 2020. (2020 Oct) Brain Struct Funct. 1:3. https://doi.org/10.1007/s00429-020-02149-9 Volledige tekst
- Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome. Kummeling, J., Stremmelaar, D.E., Raun, N. et al. . Mol Psychiatry (2020 May). https://doi.org/10.1038/s41380-020-0725-5 Volledige tekst
- Distinct Pathogenic Genes Causing Intellectual Disability and Autism Exhibit a Common Neuronal Network Hyperactivity Phenotype. Frega M, Selten M, Mossink B, Keller JM, Linda K, Moerschen R, Qu J, Koerner P, Jansen S, Oudakker A, Kleefstra T, van Bokhoven H, Zhou H, Schubert D*, Nadif Kasri N*. Cell Rep. 2020 Jan 7;30(1):173-186.e6. doi: 10.1016 Volledige tekst
- 2017 - 2022 Schizophrenia (SZ) is a serious mental illness characterized by frequent episodes of hallucination, delusions, and cognitive disabilities. SZ represents one of the major challenges for society, with large unmet patient needs and substantial health care costs. Synaptic dysfunction has recently been implicated in the pathophysiology of SZ, yet the precise mechanisms remain elusive. The SYNSCHIZ project targets synaptic dysfunction at multiple levels of investigation, from its genetic underpinnings through experimental investigation of electrophysiological properties in stem cell derived neurons and advanced mathematical modeling up to the level of brain network dysfunction in individuals with SZ. Thus, SYNSCHIZ aims to uncover how SZ risk genes yield aberrant neuronal excitability and brain connectivity to determine novel pathways and mechanisms. Meer informatie
- 2021 - 2025 Epilepsy is a common neurological disease, affecting approximately 180,000 people in the Netherlands. Treating childhood-onset genetic epilepsies is challenging. This project brings together researchers with expertise in epilepsy, neuropathology and neurophysiology to elucidate the mechanisms underlying altered neuronal network function in epilepsy, using human brain tissue and human cell models. Meer informatie