Kim lab studies how the brain establishes complex yet specific neural circuits during development and postnatal periods. Abnormal formation of the brain and neural circuits is linked to neurodevelopmental and psychiatric disorders including autism spectrum disorders, intellectual disability, mood disorders, and schizophrenia. Identification of cellular and molecular mechanisms of brain circuit establishment may lead to a better understanding of the pathogenesis underlying neurological disorders affecting cognition, emotion, and social interaction.
Neural stem cell/progenitor homeostasis in the brain
Balanced control of neural stem cell/progenitor proliferation, maintenance, neurogenesis and astrocyte production is crucial in generating functional neural circuits during brain development and in adults. Aberrant genesis and differentiation of neural progenitors are implicated in many neurological diseases. However, the regulatory mechanisms and decisive molecules of neural progenitor homeostasis remain poorly understood in the field. There are cross-talks among neurotrophic factors, mammalian target of rapamycin (mTOR), and glycogen synthase kinase-3 (GSK-3) signaling pathways in the brain. We study if cooperation of these molecules plays a key role in the maintenance and further differentiation of neuronal and astrocyte progenitor pools during brain development and in adults.
Regulation of pyramidal neuron positioning and differentiation in the brain
Formation of neural circuits depends on positioning and differentiation of neurons. Positioning and dendritic arborization are fundamental processes during pyramidal neuron development in the brain. Abnormalities in these processes cause several types of brain malformations and are associated with neurodevelopmental disorders. We study mechanisms of abnormal positioning and differentiation of cortical and hippocampal pyramidal neurons in mouse models of neurodevelopmental disorders. We focus on molecules involved in neurotrophin, mTOR, and MACF1 signaling pathways.
Development of GABAergic inhibitory neurons and neurological diseases
Generation and differentiation of GABAergic inhibitory neurons play critical roles in the generation of brain circuitry and cognitive and emotional behaviors. Autism-like behaviors and intellectual dysfunction are frequently caused by altered inhibitory signaling due to abnormal GABAergic inhibitory neurons in humans and animal models of autism and intellectual disability. Molecular mechanisms for inhibitory neuron generation and positioning in the brain remain largely elusive, which has hindered research into potential treatments for neurodevelopmental and psychiatric disorders. Using multiple genetic mouse models, we study inhibitory neuron development.
Experimental techniquesMouse genetics
- Mouse behavioral testing
- In utero manipulation of rodent brains
- Ex vivo preparations of brain tissues
- Stereotaxic gene delivery using viruses
- Neural circuit analysis using genetic tools
- Neural cell and slice culture
- Molecular and biochemical techniques
- Time-lapse and high resolution imaging