Everything that makes us human is contained within 1.4 kg of tissue: the human brain, an extraordinary organ defined by its immense complexity and energy-efficient computational power. In the Knoblich lab, we are fascinated by how this complex architecture arises during development—how distinct neuronal cell types are specified, how they migrate to their precise locations, and how they assemble into functional circuits. To investigate these fundamental processes, we pioneered cerebral organoids: patient-derived three-dimensional tissue models generated from human pluripotent stem cells that faithfully recapitulate human neurodevelopment. Beyond modeling early embryonic brain development, our organoids now allow us to explore protracted postnatal neurodevelopmental processes, such as interneuron migration and functional network assembly. By combining organoid technology with spatial transcriptomics, single-cell genomics, multiplexed electrophysiology, and viral circuit tracing, we decipher the biological mechanisms behind severe neurodevelopmental and neuropsychiatric conditions, including autism spectrum disorders, epilepsy, and brain malformations.

We aim to decipher the fundamental biological principles of human brain development and understand how genetic perturbations cause severe neurodevelopmental and functional brain disorders. To achieve this, we combine advanced human organoid models with functional genetic screening, trans-synaptic circuit mapping, and electrophysiology across multiple scales—from single-cell gene regulatory networks to functional neural circuit activity. Ultimately, our vision is to establish predictive, multimodal models that bridge experimental neurobiology and clinical applications, enabling the translation of cellular and network-level insights into novel diagnostic and therapeutic strategies.