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

Adjunct Professor
Head, Neuroscience Research Laboratory, A.I. duPont Hospital for Children

Contact

Department of Research
A.I. duPont Hospital for Children
1600 Rockland Road, Room H3B-341
Wilmington, DE 19899

Phone: (302) 651-6701
Fax: (302) 651-6767
E-mail: twiss@medsci.udel.edu

Education

B.A.: College of Charleston
M.D./Ph.D.: Medical University of South Carolina
Postdoctoral: Stanford University

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.

Selected Publications

J.L. Twiss and J. van Minnen. New insights into neuronal regeneration: the role of axonal protein synthesis in pathfinding and axonal extension. J Neurotrauma, in press.

D.E. Willis and J.L. Twiss. Evolving roles of axonally synthesized proteins in regeneration. Current Opinion in Neurobiology, in press.

G.J. Bassell and J.L. Twiss. RNA exodus into Israel: RNA controlling function in the far reaches of the neuron. EMBO Reports, in press.

D.E. Willis, K-W. Li, J-Q. Zheng, A. Smit, T.K. Kelly, T. Merianda, J. Sylvester, J. van Minnen, and J.L. Twiss (2005). Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons. J Neurosci 25:778-791.

F. Bolognani, M.A. Merhege, J.L. Twiss, and N.I. Perrone-Bizzozero (2004). Differential localization of the RNA-binding protein HuD in hippocampal neurons: association with polysomes and upregulation during contextual learning. Neurosci Letters 371:152-157.

R. Molteni, J.Q. Zheng, Z. Ying, and F. Gomez-Pinilla, and J.L. Twiss (2004). Voluntary exercise increases axonal regeneration from sensory neurons. PNAS, USA 101:8473-8478.

K.W. Dabney, M. Ehrenshteyn, C.A. Agresta, J.L. Twiss, G. Stern, L. Tice, and S.K. Salzman (2003). A model of experimental spinal cord trauma based on computer-controlled intervertebral distraction: characterization of graded injury. Spine 29:2357-2364.

J. Chang, J. Dragich, N.C. Schanen and J.L. Twiss (2003). Persistent TrkA activity is necessary to maintain transcription in neuronally differentiated PC12 cells. J Biol Chem 278:42877-42885.

S. Hanz, E. Perlson, D. Willis, J-Q. Zheng, M. Kohler, J. van Minnen, A. Sabbon, J.J. Huerta, M. Koltzenberg, J.L. Twiss, and M. Fainzilber (2003). Axoplasmic importins enable retrograde injury signaling in lesioned nerve. Neuron 40:1095-1104.

D-Y. Wu, J-Q. Zheng, M.A. McDonald, B. Chang, and J.L. Twiss (2003). PKC Isozymes in the Enhanced Regeneration of Retinal Neurites after Optic Nerve Injury. Invest Ophth Visual Sci 44:2783-2790.

J-Q. Zheng, T.K. Kelly, B. Chang, S. Ryazantsev, A.K. Rajasekaran, K.C. Martin, J.L. Twiss (2001). A functional role for intra-axonal protein synthesis during axonal regeneration from adult sensory neurons. J Neurosci 21: 9291-9303.

J.L. Twiss, D.S. Smith, B. Chang and E.M. Shooter (2000). Translational control of ribosomal protein L4 is required for rapid neurite extension. Neurobiol Dis 7: 416-428.

J.L. Twiss, H.G. Wada, K.S. Fok, S.D.H. Chan, A.N. Verity, G.T. Baxter, E.M. Shooter, and H.H. Sussman (1998). Duration and magnitude of NGF signaling depends on the ratio of p75LNTR to TrkA. J Neurosci Res 51: 442-453.

Canossa, M., Twiss, J.L., Verity, A.N., and Shooter, E.M. (1996). p75NGFR and TrkA receptors collaborate to rapidly activate a p75NGFR-associated protein kinase. EMBO J 15: 3369-3376.

J.L. Twiss and E.M. Shooter (1995). NGF promotes Neurite Regeneration in PC12 Cells by Translational Control. J Neurochem 64: 550-557.