Research in my lab is in three areas:
1) mechanisms of neuronal regeneration after spinal cord injury;
2) mechanisms of mRNA transport to synapses on neuronal dendrites;
3) mechanisms that produce resistance to neurodegeneration in mouse models of human neurodegenerative disorders.

Spinal cord injuries interrupt the long connections between the brain and spinal cord that mediate motor and sensory function; finding ways to induce regeneration of these pathways has been the “Holy Grail” of spinal cord injury research for over 100 years. My laboratory’s “Axon Regeneration Project” seeks to find ways to induce the regeneration of axons of the corticospinal tract that control voluntary movement. Even limited regeneration of this critical pathway could vastly improve quality of life for people with spinal cord injuries. Our experiments take advantage of mice in which molecular pathways involved in regeneration are genetically altered. The goal is to identify pathways that could be targeted by drugs, gene therapy, or other therapeutic interventions to promote functional regeneration.

The second major focus of research is on the mechanisms underlying the transport of mRNAs to synaptic sites on dendrites. This project is based on our discovery in 1982 that protein synthetic machinery is selectively positioned at postsynaptic sites on dendrites. Local translation of mRNAs at synapses plays an important role in activity-dependent synaptic modifications that underlie memory consolidation. Moreover, increasing evidence suggests that this basic mechanism is disrupted in Fragile-X Mental Retardation Syndrome and perhaps in other autism spectrum disorders. Our studies focus on the mRNA for the immediate early gene Arc, which is strongly induced by synaptic activity and learning experiences. Arc mRNA is rapidly transported into dendrites where it docks selectively at active synapses. We use live cell imaging and confocal microscopy to track the transport of fluorescently labeled Arc mRNA and define the mechanisms underlying the selective docking of Arc mRNA at the base of dendritic spines. We are also exploring how the translation and degradation of Arc mRNA is controlled.

The third focus of research follows up on our discovery that mice carry genes that confer resistance to neurodegeneration. Remarkably, resistance is up-regulated in an age-dependent fashion in transgenic mice that carry a human gene that causes Huntington’s Disease. Ongoing studies explore the molecular mechanisms that generate this remarkable phenotype.