The overall focus of my research is on how nerve cells create and maintain their connections with each other, and how synapses are modified by experience and after injury (synaptic plasticity). One component of the research follows on our discovery of the fundamental mechanism underlying local protein synthesis at synapses, which revealed a previously unknown aspect of neuronal cell biology. We were the first to advance the now well-accepted idea that local protein synthesis at synapses plays a critical role in enduring forms of synaptic plasticity and memory. Subsequent studies contributed to the understanding of mechanisms underlying the transport of mRNA into dendrites, selective docking of mRNA at active synapses, and activity-dependent mechanisms of mRNA decay. This core idea drove research in the fields of neuroscience and cell biology that now involves hundreds of other labs, leading to our current understanding that local protein synthesis plays a pivotal role in normal synaptic function, and that disorders of synaptic protein synthesis may underlie important developmental disorders including Fragile-X Mental Retardation Syndrome and autism spectrum disorders.
A major component of my research over the past 2 decades has been on axon regeneration following spinal cord injury (SCI). Our research team collaborated with Zhigang He’s team and others on a breakthrough report showing that conditional deletion of PTEN enabled unprecedented regeneration of corticospinal tract (CST) axons after SCI. Since then, we have developed approaches to enable regeneration via AAVshRNA-mediated knockdown and demonstrated that CST regeneration is accompanied by recovery of skilled motor function.
A major recent research focus has been on the design and deployment of AAV vectors to deliver gene modifying cargoes to enhance regenerative capacity after injury. Of particular interest are AAVs that undergo retrograde transport (retro-AAVs), which can deliver cargoes to neurons in the brain that give rise to spinal pathways.
Our laboratory uses a variety of techniques ranging from molecular biology, especially in situ hybridization, immunohistochemistry, electron microscopy, light microscopy including light sheet microscopy, neurophysiology, and behavioral assays of sensory and motor function. Our research is supported by grants from the National Institutes of Health and private donations.
Training of graduate students and postdoctoral fellows is very important to me, and I’m greatly honored to have received the NINDS Story Landis Award for Outstanding Mentorship in 2020.
