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College of Arts & Sciences
Department of Biological Sciences


Faculty & Staff Directory

Jeff Twiss

SmartState Chair in Childhood Neurotherapeutics
Department of Biology
University of South Carolina

Office: CLS 707A
Phone Number: 803-777-9215 803-777-9216 (lab)
Email: twiss@mailbox.sc.edu
Website: USC Center for Childhood Neurotherapeutics

Lab members:

  • ·       Ashley Kalinski, Post-doctoral Fellow in Biological Sciences,Drexel University, 2015
  • ·       Seung Joon Lee, Post-doctoral Fellow (lee346@mailbox.sc.edu), Ph.D. in Biological Sciences, Seoul National University, Korea, 2006
·       Sharmini Miller-Randolph, Research Technician (mille974@mailbox.sc.edu), B.S. in Biology, Vorhees University, 2001
·      Amar Kar NathPost-doctoral Fellow, (amarnathkar@gmail.com), Ph.D. in Neuroscience, Northwestern Unversity, Chicago, 2009
  • ·       Priyanka Patel, Post-doctoral Fellow, Ph.D. in Physiology and Endocrinology, University Laval, 2015
  • ·       Pabitra Sahoo, Post-doctoral Fellow, (sahoop@mailbox.sc.edu),  Ph.D. in Biotechnology, National Centre for Cell Science, University of Pune, India, 2014
    ·       Terika Smith, Post-doctoral Fellow, Ph.D. in Biomedical Sciences, University of South Carolina, 2014
    ·     Elizabeth Thames, Research Technician (elthames@mailbox.sc.edu), M.S. in Biological Sciences, University of South Carolina
  • ·       Jeff Twiss, Professor and SmartState Chair in Childhood Neurotherapeutics (twiss@mailbox.sc.edu), M.D., Ph.D. in Molecular & Cellular Biology, Medical University of South Carolina, 1990/1992

Research Description:

Our research focuses on neural repair mechanisms, specifically on how to utilize these mechanisms to improve recovery after injury of the nervous system.  Long range communication in the nervous system is provided through the axonal processes that connect neurons with their targets.  These cytoplasmic processes can extend for several centimeters in rodents and a meter or more in larger mammals like humans.  Disruption of this communication pathway, either through injury or disease, often results in permanent loss of function unless neural connections can be restored.  Our work aims to restore neural function by finding means to improve regeneration of axons.  However, the general mechanisms that we study also impact on neural function, synaptic plasticity, and development.

Both the intrinsic growth capacity of neurons and the extrinsic environment that the injured neurons are exposed to affect neural repair.  In the brain and spinal cord, the extrinsic environment actively blocks regeneration, particularly after injury.  This does not occur in peripheral nerves, but even there regeneration is painstakingly slow with axons growing only 1-2 mm each day.  Our work concentrates on the neuron’s intrinsic mechanisms for regeneration that we suspect can be utilized to both accelerate regeneration and overcome growth inhibitory environments. 

Several years ago, our lab showed that mature axons are capable of locally synthesizing new proteins (Zheng et al., 2001).  This is a mechanism that was thought to be restricted to developing neurons, but it is now clear that some neurons maintain this capability into adulthood.  Several stimuli are now known to activate translation in axons including injury.  We now know that several hundred different mRNAs are transported into axons and these locally synthesized proteins have quite diverse functions.   Some proteins allow for retrograde signaling, others function locally for growth of the axon, and others have as yet unrecognized functions.  It is not clear how the neuron knows which mRNAs to localize and when and where to translate these mRNAs.  Both mechanisms are surprisingly selective at the mRNA level providing precise spatial and temporal regulation of protein levels within axons.  Our lab team is unraveling the molecular pathways and players that underlie these events and using this knowledge to develop new strategies for neural repair.  

Our research is funded by grant awards from NIH (P01-NS055976, R01-NS041596, R01-NS089633), Department of Defense/US Army Medical Research Program (W81XWH-13-1-0308), the US-Israel Binational Science Foundation (2011329), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.  Dr. Twiss is the USC Childhood Neurotherapeutics Chair in the South Carolina SmartState Endowment Program.  

Publications (since 2010):

T. Ma, A. Campana, P. Lange, H.-H. Lee, K. Banerjee, J.B. Bryson, L. Mahishi, S. Alam, R. Giger, S. Barnes, S. Morris, D.E. Willis, J.L Twiss, M. Filbin, and R. Ratan. (2010). A large scale chemical screen for regulators of the arginase 1 promoter identifies the soy isoflavone, daidzein as a clinically approved, small molecule that can promote neuronal protection or regeneration via a cAMP-independent pathway. J Neurosci 30:739-48.

S. Yoo, E.A. van Niekerk, TT. Merianda and J.L. Twiss. (2010). Dynamics of axonal mRNA transport and implications for peripheral nerve regeneration.  Exper Neurol 223:19-27.

D. Vuppalanchi, J. Coleman, S. Yoo, T.T. Merianda, A.G. Yadhati, J. Hossain, A. Blesch, D.E. Willis, and J.L. Twiss. (2010). Conserved 3'UTR sequences direct subcellular localization of chaperone protein mRNAs in neurons. J Biol Chem 285:18025-38.

D.E. Willis and J.L. Twiss. (2010).  Regulation of protein levels in subcellular domains through mRNA transport and localized translation.  Molec Cell Prot 9:952-62.

C.J. Donnelly, M. Fainzilber, and J.L. Twiss. (2010). Subcellular communication through RNA transport and localized protein synthesis.  Traffic 11:1498-505.

S. Li, J.J. Overman, D. Katsman, S.V. Kozlov, C.J. Donnelly, J.L. Twiss, R.J. Giger, G. Coppola, D.H. Geschwind, and S.T. Carmichael. (2010). An age-related sprouting transcriptome provides molecular control of axonal sprouting after stroke.  Nature Neurosci 13:1496-504.

L.F. Gumy, G.S.H. Yeo, Y-C. L. Tung, K. Zivraj, D.E. Willis, G. Coppola, B.Y.H. Lam, J.L. Twiss, C.E. Holt, and J.W. Fawcett. (2011). Global transcriptome analysis reveals differences between embryonic and adult dorsal root ganglion axonal mRNAs that are implicated in axonal growth and pain. RNA 17:85-98.

S. Barrientos, N.W. Martinez, S. Yoo, J.S. Jara, S. Zamorano, C. Hetz, J.L. Twiss, Alvarez J., and Court F. A. (2011).  Axonal degeneration is mediated by the mitochondrial permeability transition pore. J Neurosci 31:966-978. {This work was editorially featured in ‘This Week in Neuroscience’ J Neurosci 31(3):i}

D.E. Willis and J.L. Twiss. (2011). Profiling axonal mRNA transport. Methods Molec Biol 714:335-352.

B. Akten, MJ.. Kye, H. Le, S. Singh, J. Huang, T.T. Merianda, M.H. Wertz, D. Nie, J.L. Twiss, C.E. Beattie, J. Steen, and M. Sahin. (2011).  A novel interaction of SMN and HuD with cpg15 mRNA rescues motor neuron axonal deficits.  Proc Natl Acad Sci, USA 108:10337-42.

S. Yoo and J.L. Twiss. (2011). The road not taken: new destinations for yeast mRNAs on the move.  EMBO J 30:3564-6.

C.J. Donnelly, D.E. Willis, M. Xu, C. Tep, C. Jiang, S. Yoo, N.C Schanen, C.B. Kirn-Safran, J. van Minnen, A. English, S.O. Yoon, G.J. Bassell, and J.L. Twiss. (2011).  Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity.  EMBO J 30:4665-4677.  {This work was editorially featured by R Perry and M Fainzilber, ‘Have You Seen: When Zip-Codes are in Short Supply’ (2011) EMBO J 30:4520-2} 

D.E. Willis, M. Xu, C.J. Donnelly, C. Tep, M. Kendall, M. Erenstheyn, A. English, N.C. Schanen, C.B. Kirn-Safran, S.O. Yoon, G.J. Bassell, and J.L. Twiss. (2011). Axonal localization of transgene mRNA in mature PNS and CNS neurons.  J Neurosci 31:14481-7.

K. Ben-Yaakov, S. Dagan, Y. Segal-Ruder, O. Shalem, D. Vuppalanchi, D.E. Willis, D. Yudin, I. Rishal, A. Blesch, Y. Pilpel, J.L. Twiss, and M. Fainzilber. (2012).  Axonal Transcription Factors Signal Retrogradely In Lesioned Peripheral Nerve.  EMBO J 31:1350-63.  {This work was editorially featured by V di Liberto and V Cavalli, ‘Have You Seen: Ready, STAT, Go – Transcription Factors on the Move’ (2012) EMBO J 31:1331-3}

D. Vuppalanchi, T.T. Merianda, A. Pacheco, C.J. Donnelly, G. Williams, S. Yoo, R.R. Ratan, D.E. Willis, and J.L. Twiss.  (2012).  Lysophosphatidic acid differentially regulates axonal mRNA translation through 5’ UTR elements.  Molec Cell Neurosci 50:136-46.

R. Ben-Tov Perry, E. Doron, E. Iavnilovitch, I. Rishal, S. Dagan, M. Tsoory, G. Copolla, M.K. McDonald, D. Geschwind, J.L. Twiss, A. Yaron, M. Fainzilber. (2012). Subcellular Knockout of Importin β1 Perturbs Axonal Retrograde Signaling.  Neuron 75:294-305.  {This work was editorally featured with a Pod-Cast Video in Neuron 75 issue 2}

A. Pacheco-Garcia and J.L. Twiss.  Cap-independent translation occurs in sensory axons.  PLoS One 7:e40788.

Spillane, A. Ketschek, C.J. Donnelly, J.L. Twiss, and G. Gallo. (2012).  Nerve Growth Factor-induced Formation of Axonal Filopodia and Collateral Branches Involves the Intra-Axonal Synthesis of Regulators of the Actin Nucleating Arp2/3 Complex.  J Neurosci 32:17671-89.

T.T. Merianda, D. Vuppalanchi, S. Yoo, A. Blesch, and J.L. Twiss. (2013). Axonal Transport of Neural Membrane Protein 35 mRNA Increases Axon Growth. J Cell Sci 126:90-102.

C.J. Donnelly, M. Park, M. Spillane, S. Yoo, A. Pacheco, C. Gomes, D. Vupplanchi, M.K. McDonald, H.H. Kim, T.T. Merianda, G. Gallo, and J.L. Twiss. (2013). Competition Between b-actin and GAP-43 mRNAs for Axonal Transport Supports Distinct Modes of Axonal Growth. J Neurosci 33:3311-22.  {This work was editorially featured in ‘This Week in Neuroscience’ 33(8):i}

T.T. Merianda, C. Gomes, S. Yoo, D. Vuppalanchi, and J.L. Twiss. (2013). Axonal localization of Neuritin/CPG15 mRNA in neuronal populations through distinct 5' and 3' UTR elements. J Neurosci 33:13735-42.

S. Yoo, C.J. Donnelly, D. Vuppalanchi, A.L. Kalinski, H.H. Kim, P. Kim, T.T. Merianda, D.E. Willis, N.I. Perrone-Bizzozero, and J.L. Twiss.  (2013).  Axonally localizing GAP-43 mRNA targeted by the HuD-binding site-containing 3’UTR induces axon length elongation during nerve regeneration.  J Neurochem 126:792-804.

T.T. Merianda and J.L. Twiss. (2013).  Peripheral nerve axons contain machinery for co-translational secretion of axonally generated proteins.  Neurosci Bulletin 29:493-500.

M. Spilane, A. Ketschek, T.T. Merianda, J.L. Twiss, and G. Gallo. (2013).  Mitochondria Coordinate Axonal Filopodial Dynamics,  and Sites of Axon Branching and Sites of through Preferential Intra-Axonal Protein Synthesis. Cell Reports 5:1564-75.

B.J. Harrison, R.M. Flight, C. Gomes, G.Venkat, U. Sankar, J. Twiss, E. Rouchka, and J.C. Petruska.  (2014). IB4-binding sensory neurons express a novel 3’ UTR-extended isoform of CAMK4 that is associated with its localization to axons.  J Comp Neurol 522:308-36.

S.J. Lee, A.L. Kalinski, and J.L. Twiss.  (2014).  Awakening the stalled axon – Surprises in CSPG gradients.  Submitted to Exp Neurol. 254:12-7.

C. Gomes, T.T. Merianda, S.J. Lee, S. Yoo, and J.L. Twiss. (2014). Molecular Determinants of the Axonal mRNA Transcriptome.  Devel Neurobiol 74:218-32.

R. Villegas, N. Martinez, J. Lillo, P. Pihan, D. Hernandez, J.L. Twiss, and F. Court. (2014).  Calcium release from intra-axonal ER leads to axon degeneration through mitochondrial dysfunction. J Neurosci. 34:7179-7189.

T.T. Merianda, J. Coleman, H.H. Kim, H. Rauvala, A. Blesch, S. Yoo, and J.L. Twiss.  (2015). Axonal Amphoterin mRNA is Regulated by Translational Control and Enhances Axon Outgrowth.  J Neurosci 35:5693-706.

A.L. Kalinski, R. Sachdeva, C. Gomes, S.J. Lee, Z. Shah, J. Houle, and J.L. Twiss.  (2015).  mRNAs and protein synthetic machinery localize into regenerating spinal cord axons when they are provided a substrate that supports growth.  J Neurosci 35:10357-70 (COVER IMAGE).

A. Kalinski, T. Hines, D.S. Smith, and J.L. Twiss. Neuronal transport and spatial signaling mechanisms in neural repair.  Encylopedia of Cell Biology, Elsevier Press, Eds. RA Bradshaw and P Stahl in press.

E. Doron-Mandel, S. Alber, J.A. Oses, K.F. Medzihradszky, A.L. Burlingame, M. Fainzilber, J.L. Twiss, and S.J. Lee.  Isolation and Analyses of Axonal Ribonucleoprotein Complexes.  Submitted to Methods in Cell Biology: Neuronal Cells, Elsevier Press, ed. K. Pfister, in press.

J.L. Twiss and T.T. Merianda.  Old dogs with new tricks – Intra-axonal Translation of Nuclear Proteins.  Neural Regeneration Research in press.

Link for publications in PubMed