Neurodevelopmental disorders encompass a broad constellation of conditions including intellectual disability, epilepsy, autism, schizophrenia, and other neuropsychiatric conditions. One emerging theme in the field is that disrupted inhibitory neuronal development and function is found in association with many neurologic and psychiatric disorders. This would be consistent with the growing body of knowledge that inhibitory neurons are highly diverse and key for virtually all aspects of neurobiology from neural circuit development to modulating neuronal activity to information processing.
In the Chao Lab, we integrate cross-species approaches in humans to uncover the genetic etiologies of neurodevelopmental disorders, fruit flies to elucidate the molecular pathways, and mice to explore the cascade of events in the mammalian brain. A wide variety of approaches and techniques are employed in our laboratory including genetically engineered mouse and fruit fly models, structural and functional analyses with electrophysiology, confocal and super-resolution imaging, transcriptomics, molecular and cellular assays, and comprehensive behavioral profiling. Neurodevelopmental disorders that we study include genetic syndromes characterized by epilepsy, autism, ataxia, leukodystrophy, and/or neurodegeneration. These syndromes are due to a variety of genetic and molecular alterations including transcription factor dysfunction (EBF3), protein translation dysfunction (EIF2AK1, EIF2AK2, EIF4A2), and synaptic machinery (STXBP1, presynaptic scaffolding proteins).
Our goal is to decipher how genetic alterations perturb the balance of excitation and inhibition in the brain, impact cerebro-cerebellar circuits in autism and ataxia, impact neural development across multiple brain structures, and lead to abnormal neurologic output.