675526-7ab02c10-3dd2-4650-854b-704edeb354f1
Position
Associate Director
Company
Burke Neurological Institute
Bio
My early work on transcriptional regulation of gene expression during brain development hinted that a degree of post-transcriptional regulation was critical for regulating protein levels in developing glial cells. I wanted to delve further into post-transcriptional regulation during my post-doctoral work with Jeffery Twiss, who was beginning to study the role of axonal protein synthesis. Localized protein synthesis provides a means for the distal processes of neuron to rapidly and autonomously respond to its environment. Although the capability of dendrites to locally synthesize new proteins was well studies, it had long been believed that mRNAs and protein translation machinery were actively excluded from axons and that all axonal protein was thus derived from the cell body. At the time I joined the Twiss lab, they had shown that mRNAs localize into regenerating sensory axons, but there was scant evidence pointing to either the identity of the mRNAs that undergo axonal localization or how this process is regulated. The majority of my initial work focused on identifying transcripts that could localize into regenerating axons of sensory neurons and subsequently be available for local translation, with the goal of understanding the molecular mechanisms that allow a neuron to respond to injury. I focused on determining which proteins can be locally synthesized in regenerating axons and to begin to understand how their axonal levels can be modulated. I developed live cell imaging and RNA detection methodologies that can be used to dissect axonal transport and localized translational mechanisms. Joining the Twiss lab at a critical time in the infancy of a newly developing field of axonal biology allowed me to significantly contribute to our understanding of the prevalence and importance of axonal RNA transport and local translation. We have demonstrated that axonal RNA localization occurs in both PNS and CNS neurons and that inhibiting this process leads to a failure of regeneration in the PNS, resulting in abnormal repair and sensory behavior. I am currently focusing on understanding how aberrant axonal mRNA transport and local synthesis may contribute to pathophysiologic states, such as neuropathy, and to genetic disorders that result from axonal dysfunction. In addition to my research focus, I have assumed increasing administrative roles over the last three years. In 2016, I was appointed Associate Director of the Burke Neurological Institute, and in 2018 I was appointed as Director of Research for the Burke-Blythedale Pediatric Neuroscience Research Collaboration. These positions afford me the opportunity to make strategic decisions regarding the direction of the Institute and the research collaboration, and to provide critical input into new and ongoing research programs. I oversee clinical research programs focused on brain injury and spinal cord injury in both children and adults.