Research Interests

Research in our laboratory seeks to understand the fundamental principles that govern neuronal morphogenesis and plasticity. Using a combination of state-of-the-art live cell imaging, chemical genetics and protein biochemistry, we are pursuing two major lines of research.

Axon specification and neuronal polarity
The polarization of axons and dendrites determines the ability of neurons to integrate and transmit information in the brain. We are interested in elucidating the cell intrinsic signaling circuitry underlying axon specification. Using fluorescent biosensors to monitor the activation state of “polarity regulating” signaling components, in combination with a chemical genetics strategy to perturb signaling activities with high temporal resolution, we hope to capture the initial signaling events that trigger axon formation. We are particularly interested in identifying feedback circuits that amplify the initial symmetry-breaking event and consolidate axon growth. Our work is also directed at understanding how polarized membrane traffic to the emerging axon is regulated.

Dendritic spine morphogenesis and synaptic plasticity
Most excitatory synapses in the brain terminate on dendritic spines, small membrane protrusions on dendrites that come in many different shapes and sizes. Structural changes in spines may represent a form of functional synaptic plasticity and memory storage. Our research in this area is focused on the following two topics:

(a)    The Ras/MAPK pathway is activated in response to synaptic inputs in glutamatergic neurons and contributes to the regulation of an array of cellular functions underlying synaptic and structural plasticity. We wish to understand how the small GTPase Ras decodes synaptic Ca2+ inputs and engages the MAPK pathway in an activity-dependent manner.

(b)    Abnormalities of spine morphology have been associated with cognitive disorders including mental retardation and neurodegenerative diseases. We are studying a group of genes encoding Guanine Nucleotide Exchange Factors (GEFs) and GTPase Activating Proteins (GAPs) for Rho GTPases which, when mutated, have been associated with mental retardation. We wish to understand how specific mutations in these genes affect Rho signaling pathways and ultimately result in abnormal spine morphogenesis and synaptic defects.