Investigating the functional impact of SHANK2 mutations in differentiated human induced pluripotent stem cells as a model for neurodevelopmental disorders

• Applicant: Dr. Simone Berkel
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 407247919

To gain novel insight into the pathogenesis of neurodevelopmental disorders such as intellectual disability and autism, we plan to analyze the functional impact of SHANK2 mutations in differentiated human induced pluripotent stem cells. SHANK2 encodes for a postsynaptic scaffolding protein at glutamatergic synapses in the brain, which plays a central role in synapse formation, maintenance and function. To date, several patients with intellectual disability and autism have been identified with SHANK2 de novo mutations. Investigating the impact of different SHANK2 mutations on neuronal differentiation, synapse formation and general neuronal function, will elucidate the role of SHANK2 during early human neuronal development and will help to identify the molecular and cellular alterations in individuals with SHANK2 deletions. The improved understanding of the pathogenesis of autism and intellectual disability gained by this study can be used for the development of pharmacological intervention strategies.

• DFG Programme: Research Grants