Research and Clinical Interests

The long-range goal of my research program is to understand how synapses and functional neural circuits are generated.

The structure of the nervous system varies tremendously across phylogeny; organisms such as the C. elegans function with a few hundred neurons, whereas humans have tens of billions. Yet communication in all neural circuits is controlled by a remarkably similar, highly specialized site of cell-cell contact known as a synapse. The goal of my research program is to understand how excitatory spine synapses are formed and lost, and what impact the normal morphology and numbers of these structures have on brain function. Because the excitatory synapse is likely to be central to a number of diseases such as addiction, Alzheimer's disease, and autism, our research will have broad impact.

To date, our work has focused on elucidating the molecular mechanisms that guide how excitatory spine synapses are formed and lost, and what impact the normal morphology and numbers of these structures have on brain function. In addition we are developing a set of simple but novel genetically encoded fluorescent phosphorylation reporters (Phos) that allow us to visualize and quantify both increases and decreases in tyrosine kinase signaling induced by specific kinases. Building on the tools, techniques, and expertise we have developed we are now turning to the issue of how neurons move to the proper locations within the adult brain.

To generate functional neuronal circuits and form the proper synapses, neural progenitor cells must not only differentiate into the correct neuronal subtypes, they must also migrate to appropriate locations in the brain. This question is important not only to understand how circuits are formed, but because to meet the therapeutic promise in a wide range of human CNS diseases including addiction, neurodegenerative disorders, and stroke, how the migration and differentiation of endogenous neural progenitor is controlled must understand.

Overall, by integrating a reductionist approach with careful in vivo experiments we have the potential to generate transformative results that fundamentally advance our understanding of how synapses form, how neurons are guided, and how synapse density impacts circuit function. I am confident our work will continue to impact our understanding of basic nervous system function and provide new tools and strategies for functional recovery in malfunctioning neural networks.