We are using cerebral organoid technology coupled with patterning factors to generate distinct parts of the human brain. The fusion culture of different region-specific organoids (aka ‘Assembloids’) enables us to observe and measure interactions between different brain areas, such as the long-distance migration of interneurons or the generation of major axon tracts. We use this approach to study principles of human neurodevelopment and mechanisms behind human neurological disorders including epilepsy and autism.
We are studying diverse neurodevelopmental disorders that result from loss-of-function of crucial genes and/or exposure to chemical or infectious agents. Coupled with patient-derived iPSCs, we are applying Crispr gene editing technology to generate loss-of-function mutations in key genes to understand the biological mechanisms underlying various neurodevelopmental diseases including microencephaly and brain cancers. We take advantage of the latest revolution in next-generation single cell sequencing technologies and microscopy methods available on our campus to apply high throughput screening methods and detailed analysis of specific disease cases.
A major factor underlying various psychiatric disorders is perturbed diversity, connections or functions of the neurons. We are using the organoids to investigate the development and specificity of neuronal connections and complex circuitry in the brain. Towards this end, we combine cell biological assays, viral tracing as well as functional recordings to study synaptic connections and neuronal activity.