The overall research goal of my laboratory is to define cellular and molecular mechanisms mediating the development and maintenance of a functional nervous system, and the consequences of their going astray. We are interested particularly in molecules that spatially and temporally coordinate cytoskeletal reorganization at and vesicle delivery to the expanding plasma membrane of developing neurons. In my lab, we have focused on the role of the brain-enriched E3 ubiquitin ligases TRIM9 and TRIM67 in controlling cytoskeletal dynamics and vesicle trafficking during axon guidance and branching in embryonic cortical neurons. We have uncovered mechanisms by which these ligases alter the stability of growth cone filopodia and membrane delivery via exocytosis, which are critical for axon guidance and axon branching. The functions of TRIM9 and TRIM67 we have uncovered are dependent upon their ligase activity, yet surprisingly so far, independent of protein degradation, thus revealing novel roles for this post-translational modification in cytoskeletal and trafficking regulation and morphogenesis. Together with the development of microfluidic-based approaches, we are parsing new mechanisms of axon guidance. By adding neuroanatomical and behavioral studies, our work extends the molecular mechanisms regulating neuronal morphogenesis and function to disruptions in specific axon fiber tracts in vivo and compromised animal behaviors.
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