Glia-Neuron Interactions
Our lab is particularly interested in the intercellular signals that convey information between neurons and glia during homeostatic plasticity. Our previous studies suggest that glia and glia-secreted molecules are critical in the homeostatic regulation of synapse function. Impairment of these signaling modules completely abolishes synaptic homeostatic plasticity when the nervous system is challenged by perturbations. Dysfunction of these glial-expressed genes are associated with epilepsy, Autism Spectrum Disorder (ASD), and Alzheimer’s Disease. However, how these glial-derived factors affect the stability of the synapse and circuit are not clear. We are currently studying the function of glia-neuron interactions in stabilizing the synapse and circuitry using an array of electrophysiology and transcriptomics methods.
Dynamic Regulation of ECM
In the nervous system, extracellular matrix (ECM) not only provides an environment that different types of cells reside in, the dynamic regulation of ECM is also essential for shaping synapse and circuit function. We demonstrated previously that proteolytic cleavage products of ECM are important for regulating presynaptic calcium channel and neurotransmitter release. Our lab uses proteomics, electrophysiology and imaging methods to identify and study ECM molecules and their presynaptic receptors that are involved in regulating synapse physiology.
Disease Models and Transcriptomics
Maintenance of the excitation/inhibition balance and synaptic transmission by homeostatic mechanisms endows neurons and synapses with the ability to stabilize the level of function despite perturbations. Despite the fundamental importance of synaptic homeostatic plasticity, how failed homeostatic signaling leads to neurological disorders such as epilepsy, Alzheimer's disease, and autism is poorly defined. Generating disease models in Drosophila and mice will not only allow thorough analyses of how impaired synaptic homeostasis contributes to the cause and progression of the disease but is also an important step in bridging the gap between human genetics data and the cellular deficits that underlie the clinical presentation. We use CRISPR genome editing to generate genetic disease models, mapping the molecular interface between impaired homeostatic plasticity and diseases of the brain. Our bioinformatics team is also working on generating cutting-edge analytical tools and deep learning algorithms to dissect the transcriptional and epigenetic programs required in different cell types for stabilizing the nervous system.
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