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

Adjunct Professor

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

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

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

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

• Merianda TT, Lin AC, Lam JSY, et al. A functional equivalent of endoplasmic reticulum and Golgi in axons for secretion of locally synthesized proteins. Mol Cell Neurosci. 2009;40(2):128–142.
• Toth CC, Willis D, Twiss JL, et al. Locally synthesized calcitonin gene-related Peptide has a critical role in peripheral nerve regeneration. J Neuropathol Exp Neurol. 2009;68(3):326–337.
• Kumar A, Kamboj S, Malone BM, et al. Analysis of protein domains and Rett syndrome mutations indicate that multiple regions influence chromatin-binding dynamics of the chromatin-associated protein MECP2 in vivo. J Cell Sci. 2008;121(Pt 7):1128–1137.
• Yudin D, Hanz S, Yoo S, et al. Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve. Neuron. 2008;59(2):241–252.
• van Niekerk EA, Willis DE, Chang JH, Reumann K, Heise T, Twiss JL. Sumoylation in axons triggers retrograde transport of the RNA-binding protein La. Proc Natl Acad Sci U S A. 2007;104(31):12913–12918.
• Wang W, van Niekerk E, Willis DE, Twiss JL. RNA transport and localized protein synthesis in neurological disorders and neural repair. Dev Neurobiol. 2007;67(9):1166–1182.
• Willis DE, van Niekerk EA, Sasaki Y, et al. Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs. J Cell Biol. 2007;178(6):965–980.
• Bassell GJ, Twiss JL. RNA exodus to Israel: RNA controlling function in the far reaches of the neuron. Workshop on RNA control on neuronal function. EMBO Rep. 2006;7(1):31–35.
• Chang JH, Vuppalanchi D, van Niekerk E, Trepel JB, Schanen NC, Twiss JL. PC12 cells regulate inducible cyclic AMP (cAMP) element repressor expression to differentially control cAMP response element-dependent transcription in response to nerve growth factor and cAMP. J Neurochem. 2006;99(6):1517–1530.
• Twiss JL, van Minnen J. New insights into neuronal regeneration: the role of axonal protein synthesis in pathfinding and axonal extension. J Neurotrauma. 2006;23(3-4):295–308.
• Willis DE, Twiss JL. The evolving roles of axonally synthesized proteins in regeneration. Curr Opin Neurobiol. 2006;16(1):111–118.
• Willis D, Li KW, Zheng J-Q, et al. Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons. J Neurosci. 2005;25(4):778–791.
• Bolognani F, Merhege MA, Twiss J, Perrone-Bizzozero NI. Dendritic localization of the RNA-binding protein HuD in hippocampal neurons: association with polysomes and upregulation during contextual learning. Neurosci Lett. 2004;371(2-3):152–157.
• Dabney KW, Ehrenshteyn M, Agresta CA, et al. A model of experimental spinal cord trauma based on computer-controlled intervertebral distraction: characterization of graded injury. Spine. 2004;29(21):2357–2364.
• Molteni R, Zheng J-Q, Ying Z, Gomez-Pinilla F, Twiss JL. Voluntary exercise increases axonal regeneration from sensory neurons. Proc Natl Acad Sci U S A. 2004;101(22):8473–8478.
• Rajasekaran SA, Gopal J, Willis D, Espineda C, Twiss JL, Rajasekaran AK. Na,K-ATPase beta1-subunit increases the translation efficiency of the alpha1-subunit in MSV-MDCK cells. Mol Biol Cell. 2004;15(7):3224–3232.
• Chang JH, Mellon E, Schanen NC, Twiss JL. Persistent TrkA activity is necessary to maintain transcription in neuronally differentiated PC12 cells. J Biol Chem. 2003;278(44):42877–42885.
• Hanz S, Perlson E, Willis D, et al. Axoplasmic importins enable retrograde injury signaling in lesioned nerve. Neuron. 2003;40(6):1095–1104.
• Wu D-Y, Zheng J-Q, McDonald MA, Chang B, Twiss JL. PKC isozymes in the enhanced regrowth of retinal neurites after optic nerve injury. Invest Ophthalmol Vis Sci. 2003;44(6):2783–2790.
• Zheng JQ, Kelly TK, Chang B, et al. A functional role for intra-axonal protein synthesis during axonal regeneration from adult sensory neurons. J Neurosci. 2001;21(23):9291–9303.
• Twiss JL, Smith DS, Chang B, Shooter EM. Translational control of ribosomal protein L4 mRNA is required for rapid neurite regeneration. Neurobiol Dis. 2000;7(4):416–428.
• Twiss JL, Wada HG, Fok KS, et al. Duration and magnitude of nerve growth factor signaling depend on the ratio of p75LNTR to TrkA. J Neurosci Res. 1998;51(4):442–453.
• Canossa M, Twiss JL, Verity AN, Shooter EM. p75(NGFR) and TrkA receptors collaborate to rapidly activate a p75(NGFR)-associated protein kinase. Embo J. 1996;15(13):3369–3376.
• Twiss JL, Shooter EM. Nerve growth factor promotes neurite regeneration in PC12 cells by translational control. J Neurochem. 1995;64(2):550–557.

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