Jeffery L. Twiss, M.D., Ph.D.

Research Interests

Our laboratory is interested in how the nervous system responds to injury. Since the mammalian central nervous system has little capacity for repair, injury results in loss of function - such paralysis after spinal cord injury. We want to prevent or, at least, lessen such functional loss. Several lines of evidence indicate that the molecular state of a neuron before injury dictates how well that cell can respond to injury. Essentially, the neuron initially makes use of what precursor and cytoprotective molecules it has. After axonal injury, translational control of existing mRNAs is used during the first stages of nerve regeneration to expedite axonal regrowth. We have focused on two major aspects of how such control occurs. First, we want to know what intracellular signals are used to maintain transcription before injury and what extracellular stimuli contribute to this neuronal gene expression. Both trophic factors and activity contribute to maintenance of gene expression by regulating neuronal transcription factors. Second, we want to determine how the injured neuron knows which mRNAs it needs to translate after injury. Interestingly, mRNA translation after injury is specific for the mRNAs encoding protein products that are needed for regeneration. Furthermore, neuronal protein synthesis is regulated both temporally and spatially in the injured neuron. Thus, not only does the neuron know which mRNAs to translation but also when and where. The injured neurons has developed some means to the translational machinery and specific mRNAs into the regenerating axons.

Current Projects

• NINDS/NIH - Translational regulation during nerve regeneration.
• Nemours - Gene regulation after spinal cord injury.
• Nemours - Intracellular mechanisms of neural repair.

Research Group

• Tanuja Merianda, Ph.D. - Postdoctoral Fellow (Ph.D., Mysore University, India). Studying mRNA transport and trafficking of axonally synthesized proteins.
• Dianna Willis, Ph.D. - Postdoctoral Fellow (Ph.D., University of Delaware). Studying mechanisms of mRNA localization and translation in regenerating axons.
• Jun-Qi Zheng, Ph.D. - Research Associate (Ph.D., Hyogo University, Japan). Studying temporal and spatial control of mRNA translation during axonal regeneration and in activity-primed neurons.
• Jay Chang, B.S. - Graduate Student (B.S., University of California, Los Angeles). Studying the mechanisms of maintenance of gene expression in mature neurons.
• Erna van Niekerk, B.S. - Graduate Student (B.S., University of Delaware). Studying biogenesis of neuronal ribosomes and subcellular localization of neuronal ribosomal protein mRNAs.