The Ogawa Lab investigates the molecular mechanisms underlying neuropsychiatric disorders, with a particular focus on the formation, organization, and maintenance of neuronal structures such as the axon initial segment (AIS) and axo-axonic synapses. The AIS is a specialized neuronal domain essential for action potential initiation and serves as the postsynaptic site for inhibitory inputs from Chandelier cells, a unique subclass of interneurons. Disruption of AIS structure or axo-axonic synapses has been strongly implicated in neuropsychiatric and neurological disorders, including autism spectrum disorders, schizophrenia, and bipolar disorder.
Our research integrates proteomics, adeno-associated viral (AAV) vectors, and CRISPR/Cas9-based genome editing to identify and functionally characterize proteins required for AIS organization and axo-axonic synapse assembly. Using differential and proximity-based proteomic approaches, we have discovered novel AIS-enriched and axo-axonic synapse-associated proteins, including Contactin-1 (Nature Communications) and Gephyrin (PNAS), and revealed their essential roles in synapse formation and neuronal circuit integrity.
To address those fundamental biological questions, the Ogawa Lab develops innovative experimental strategies that overcome long-standing technical barriers in neuroscience. To this end, we established the Hide-and-Seek genome editing system, which enables efficient, cell-type-specific manipulation of multiple genes in vivo without the need for complex breeding of transgenic mouse lines. This platform dramatically increases experimental throughput and allows systematic functional characterization of axo-axonic synapse-associated molecular mechanisms that were previously inaccessible.
Through these approaches, the Ogawa Lab aims to uncover general principles governing neuronal polarity, synapse assembly, and circuit stability, while providing broadly applicable tools for the neuroscience community.