Mechanism and function of mRNA transport and local protein synthesis in neurons; Inherited neurological diseases resulting for altered regulation of RNA; spinal muscular atrophy; fragile x syndrome
The main research interest of our laboratory is to understand the mechanism and function of mRNA transport and local protein synthesis in neurons of the central and peripheral nervous system. We are using in vitro and in vivo models of synaptic activity and nerve injury, as well as mouse models of neurological diseases, to assess the function of mRNA regulation in axon guidance, nerve regeneration and synaptic plasticity. We have a long-standing interest in the mechanism, regulation and function of ?-actin mRNA localization to growth cones of developing axons. More recently, we have been interested how impairments in mRNA regulation may underlie spinal muscular atrophy (SMA) and fragile x syndrome (FXS), two inherited neurological diseases affecting children. Efforts are also underway to evaluate different therapeutic modalities in these mouse models. Our research utilizes a multi-disciplinary approach that involves primary neuronal culture, brain/nerve micro-dissection, viral vectors, fluorescently tagged mRNA and proteins, fluorescence live-cell imaging, and molecular and biochemical methods to isolate and characterize RNA-protein interactions. These studies will provide new insight into molecular and cellular mechanisms important for neuronal development and plasticity, as well as into defects in these pathways that underlie neurological diseases.