Research Interests

The Rho family of small GTPases regulate many key aspects neuronal function, including axonal guidance, dendritic arbor growth, and spine morphogenesis and plasticity. Efficient signal transduction often relies on the organization of signaling pathways around multi-protein complexes. Rho GTPase signaling depends on the balance of the opposing activities of GEF and GAP proteins. How these activities are organized is largely unknown, yet understanding this is important for determining how signaling specificity is achieved. It is also crucial for understanding how Rho GTPase signaling drives the cellular functions of neurons.

My laboratory is interested in two broad questions. 1) How is Rho-family GTPase signaling to the actin cytoskeleton regulated by multi-protein complexes? 2) How does the organization of these signaling pathways translate to the regulation of processes such as migration, neurite outgrowth and guidance, and synapse formation?

Our work is focused on a family of GAP proteins that contain multiple protein-protein interaction and subcellular targeting motifs. We originally identified these GAPs in a proteomic screen for neural proteins that regulate a Rac and WAVE-1 based signaling pathway. These GAPs have been implicated in human mental retardation and axonal guidance pathways suggesting they likely regulate important cellular functions during development. We are using a combination of protein interaction assays and informatics to identify how each of these GAPs are integrated into specific Rho-GTPase signaling pathways. To study how these GAP regulate cellular functions we use live imaging of fluorescently labeled GAPs, FRET, and morphometric analysis. We combine these with mouse genetics and primary cultures to study how these signaling complexes operate in vivo.