mRNA transport and local protein synthesis, their function in axon guidance and synaptic plasticity, and dysfunction in Spinal Muscular Atrophy and Fragile X Syndrome.
The major focus of our laboratory is to understand mechanisms involved in mRNA trafficking and local protein synthesis and assess their function in axon guidance, regeneration and synaptic plasticity. We are also studying how impairments in these processes may underlie defects in Spinal Muscular Atrophy and Fragile X Syndrome.
A long-standing interest to us has been the molecular mechanism, regulation and function of beta-actin mRNA transport and its local translation within growth cones of developing axons. Ongoing research suggests that the mRNA binding protein, ZBP1, may function as a bifunctional adapter molecule that links beta-actin and other mRNAs to a specific kinesin motor. We are also studying how axon guidance molecules, such as netrin, regulate local beta-actin synthesis in growth cones to influence growth cone dynamics. The role of mRNA localization and local protein synthesis in nerve regeneration is also under study using in vivo models of nerve injury. Another project is the study of Spinal Muscular Atrophy (SMA), an inherited neurodegenerative disease affecting motor neurons. SMA is caused by the reduction of the survival of motor neuron protein SMN which may play a role in mRNA localization. Another project concerns the role of local protein synthesis within dendritic spines and its function in long-term synaptic plasticity. One mRNA binding protein under study is the Fragile X Mental Retardation Protein (FMRP) whose genetic deficiency is the cause of fragile x syndrome (FXS), the most common form of inherited mental retardation.
