Research in my lab examines protein trafficking mechanisms at synapses, and seeks to understand how these mechanisms are used to regulate synaptic transmission. 

The dendrites of neurons receive and integrate inputs from hundreds or thousands of partner cells, and most of this input arrives at highly specialized sites called synapses that are distributed over the dendritic tree. Improper regulation of synaptic transmission is implicated in an enormous variety of psychiatric disorders: an imbalance of glutamatergic neurotransmission in particular has been identified in the pathophysiology of diseases ranging from schizophrenia and autism to epilepsy and addiction, and increasing evidence suggests that excitatory synapses are among the earliest targets of Alzheimer's Disease (AD) pathogenesis. A key means of synaptic regulation is the control of the number and subsynaptic position of postsynaptic neurotransmitter receptors, and so understanding the mechanisms involved has broad implications not only for understanding the etiology of many diseases but more generally for defining the cellular basis of nervous system function and disorder.

We focus on processes that operate rapidly and very locally to regulate synaptic function on a moment-to-moment basis. These mechanisms are of particular interest because they likely underlie the initial stages of memory formation, and their perturbation produces severe and long-lasting damage to synaptic and neuronal morphology. Mechanisms we are studying currently include the trans-synaptic molecular bridges that align presynaptic nerve terminals with postsynaptic specializations, the continuous internalization and recycling of synaptic receptors, and the postsynaptic actin cytoskeleton that controls postsynaptic morphology and regulates receptor trafficking in many ways.  

Understanding the complex set of molecular reactions that underlie endocytosis and other trafficking events requires examining these events in live cells. Thus, the lab has turned to high-resolution, high-speed, multi-color confocal imaging of proteins in cultured neurons as a way of examining the kinetics and spatial features of the molecular events at individual living synapses. We utilize a number of novel fluorescence assays to examine protein positioning and movement at the synapse in living cells at the highest resolution possible. These tools provide the perfect complement to whole-cell and single-channel electrophysiological assays, which naturally track receptor function at high speed but typically with little or no spatial resolution. The lab aims to combine these approaches with molecular perturbation of protein function to provide unprecedented spatial, temporal, and molecular understanding of the protein trafficking events in spines.

• Harold MacGillavry, PhD, Postdoctoral Fellow
• Emily Lu, PhD student in Molecular Medicine
• Tamar Davis, Research Assistant
• Haiwen Chen, MD/PhD student in the Program in Neuroscience
• Sarah Ransom, PhD student in the Program in Neuroscience
• Tuo Peter Li, MD/PhD student in the Program in Neuroscience

• Nicholas Frost, MD/PhD, moved to residency at UCSF
• Justin Kerr, PhD, moved to Postdoctoral Fellow at NIH
• Mustafa Chowdhury, Postdoctoral Fellow
• Minerva Contreras, Research Assistant
• Ella Kong, Research Assistant