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Ruben Eggers

Technician

Email: r.eggers@nin.knaw.nl
Phone: +31 20 5665510
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Research

Root avulsions due to traction to the brachial plexus causes complete and permanent loss of function. Until fairly recent, such lesions were considered impossible to repair. Although reimplantation of an avulsed ventral root does lead to some motor axon regeneration, the degree of function recovery remains poor. Possible explanations can be found in the apparent inverse correlation between the distance (i.e. time) needed to reach the distal target muscle and the degree of motoneuron survival, axonal regeneration and pro-regenerative state of the peripheral nerve.

My PhD project aims to promote regeneration of motor axons towards the distal target musculature ultimately leading to improved function recovery. One of the tools used is application of gene therapy using a stealth gene switch for glial cell line-derived neurotrophic factor (GDNF) at the site of ventral root implantation. This system enables us to temporally control expression of this motoneuron survival- and regeneration promoting factor. This has led to prolonged motoneuron survival, increased distal motor axon outgrowth and improved electrophysiological responses of the distal target musculature.

Biosketch

Ruben Eggers graduated in Medical and Biological Laboratory research with a major in animal experiment and biotechnology at the Hogeschool Utrecht. He started as a technician in the Verhaagen group, conducting and supporting studies focused on improvement of function recovery using multiple intervention strategies in both CNS and PNS nerve lesion models. His expertise concerns technical aspects concerning microsurgery, intervention strategies using viral vectors, validation of recovery of function, histological processing and dataset analysis. Since June 2014, he simultaneously started as PhD student supervised by Prof. Joost Verhaagen and Prof. Martijn Malessy (LUMC).

Publications

  • M.J. Ruitenberg, R .Eggers, G.J. Boer, J. Verhaagen. Adeno-associated viral vectors as agents for gene delivery: application in disorders and trauma of the central nervous system. Methods (2002)
  • A.R .Harvey, W. Kampuis, R. Eggers, N.A .Symons, B. Blits, S. Niclou, G.J. Boer, J. Verhaagen. Intra-vitreal injection of Adeno-associated Viral Vectors Results in the transduction of Different types of retinal neurons in neonatal and adult rats: A comparison with lentiviral vectors. Mol.Cell Neurosci. (2002)
  • N.L.U .van Meeteren, R .Eggers, A.J. Lankhorst, W.H. Gispen, F.P.T. Hamers. Locomotor recovery after spinal cord contusion injury in rats is improved by spontaneous exercise. J. Neurotrauma (2003)
  • B. Blits, T. P. Carlstedt, M.J. Ruitenberg, F. de Winter, W. T. J. M. C. Hermens, P.A. Dijkhuizen, J. W. C. Claasens, R. Eggers, R. van der Sluis, L.Tenenbaum, G. J. Boer J. Verhaagen. Rescue and sprouting of motoneurons following ventral root avulsion and reimplantation combined with intraspinal adeno-associated viral vector-mediated expression of glial cell line-derived neurotrophic factor or brain-derived neurotrophic factor. Exp.Neurol (2004)
  • B.Y.Ahmed, S.Chakravarthy, R.Eggers, W.T.J.M.C.Hermens, J.Y.Zhang, S.P. Niclou, C. Levelt, F. Sablitzky, P.N. Anderson, A.R. Lieberman , J. Verhaagen. Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors. BMC Neurosci. (2004)
  • De Wit, J., Eggers, R., Evers, R. Castren E, Verhaagen, J. Long-term adeno-associated viral vector-mediated expression of truncated TrkB in the adult rat facial nucleus results in motor neuro degeneration. j.Neuroscience (2006)
  • Hendriks, W.T.J., Eggers, R., Ruitenberg, M.J., Blits, B., Hamers,F.P.T., Verhaagen, J, and Boer,G.J. Profound differences in spontaneous long term functional recovery after defined spinal tract lesions in the rat. J. Neurotrauma (2006)
  • Hendriks WT, Eggers R, Verhaagen J, Boer GJ. Gene transfer to the spinal cord neural scar with lentiviral vectors: predominant transgene expression in astrocytes but not in meningeal cells. J Neurosci Res. (2007)
  • Hendriks WT Eggers R,*, Carlstedt TP, Zaldumbide A, Tannemaat MR, Fallaux FJ, Hoeben RC, Boer GJ, Verhaagen J. Lentiviral vector-mediated reporter gene expression in avulsed spinal ventral root is short-term, but is prolonged using an immune “stealth” transgene. Restor Neurol Neurosci. (2007)
  • Eggers R, Hendriks WT, Tannemaat MR, van Heerikhuize JJ, Pool CW, Carlstedt TP, Zaldumbide A, Hoeben RC, Boer GJ, Verhaagen J. Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots. Mol Cell Neurosci. (2008)
  • Tannemaat MR, Eggers R, Hendriks WT, de Ruiter GC, van Heerikhuize JJ, Pool CW, Malessy MJ, Boer GJ, Verhaagen J. Differential effects of lentiviral vector-mediated overexpression of nerve growth factor and glial cell line-derived neurotrophic factor on regenerating sensory and motor axons in the transected peripheral nerve. Eur J Neurosci. (2008)
  • Tannemaat MR, Boer GJ, Eggers R, Malessy MJ, Verhaagen J. From microsurgery to nanosurgery: how viral vectors may help repair the peripheral nerve. Prog Brain Res. (2009)
  • Eggers R, Tannemaat MR, Ehlert EM, Verhaagen J. A spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral root avulsion and implantation. Exp Neurol. (2010)
  • Erich M Ehlert, Ruben Eggers, Simone Niclou and Joost Verhaagen Cellular toxicity following application of adeno-associated viral vector driven RNA interference in the central nervous system. BMC Neurosci. (2010)
  • Mason MR, Ehlert EM, Eggers R, Pool CW, Hermening S, Huseinovic A, Timmermans E, Blits B, Verhaagen Comparison of AAV Serotypes for Gene Delivery to Dorsal Root Ganglion Neurons. Molec. Ther. (2010)
  • Geeven G, Macgillavry HD, Eggers R, Sassen MM, Verhaagen J, Smit AB, de Gunst MC, van Kesteren RE. LLM3D: a log-linear modeling-based method to predict functional gene regulatory interactions from genome-wide expression data. Nucleic Acids Res. (2011)
  • Joanna Korecka, Marijn Schouten, Ruben Eggers, Ayse Ulusoy, Koen Bossers and Joost Verhaagen. Comparison of AAV Serotypes for Gene Delivery to Dopaminergic Neurons in the Substantia Nigra. In Tech: Viral Gene Therapy (2011)
  • Simone A. van den Berge, Miriam E. van Strien, Joanna Korecka, Anke A. Dijkstra, Jacqueline A. Sluijs,Lieneke Kooijman, Ruben Eggers, Lidia De Filippis, Angelo L. Vescovi, Joost Verhaagen, Wilma D.J.van de Berg, Elly M. Hol. The proliferative capacity of the subventricular zone is maintained in the parkinsonian brain. Brain (2011)
  • Korecka JA, Eggers R, Swaab DF, Bossers K, Verhaagen J. Modeling early Parkinson’s disease pathology with chronic low dose MPTP treatment. Restor.Neurol.Neurosci. (2013)
  • Roet KC, Eggers R, Verhaagen J. Non-invasive bioluminescence imaging of olfactory ensheathing glia and Schwann cells following transplantation into the lesioned rat spinal cord. Cell Transplantation (2012)
  • Fred de Winter, Stefan Hoyng, Martijn Tannemaat, Ruben Eggers, Matthew Mason, Martijn Malessy, Joost Verhaagen. Gene therapy approaches to enhance regeneration of the injured peripheral nerve. Eur J. Pharmacol (2013)
  • Ruben Eggers , Fred de Winter , Stefan A. Hoyng , Kasper C.D. Roet , Erich M. Ehlert, Martijn J.A. Malessy, Joost Verhaagen , Martijn R. Tannemaat . Lentiviral vector-mediated GDNF gradients after ventral root avulsion: effects on axon trapping, Schwann cell maturation and myelination. PLOS-one (2013)
  • Roet, K.C.D, Franssen, De bree, Essing, Zijlstra, Fagoe, Eggink, Eggers, Smit, Kesteren, Verhaagen. A multilevel screening strategy defines a molecular fingerprint of pro-regenerative olfactory ensheathing cells and identifies SCARB2, a protein that improves regenerative sprouting of injured sensory spinal axons. J.Neurosci. (2013)
  • Nitish D. Fagoe , Ruben Eggers , Joost Verhaagen, Matthew R. J. Mason. A compact dual promoter adeno-associated viral vector for efficient delivery of two genes to dorsal root ganglion neurons. Gene ther. (2014)
  • Stefan Hoyng, Sara Gnavi, Fred de Winter, Ruben Eggers, Takeaki Ozawa, Arnaud Zaldumbide, Rob Hoeben, Martijn Malessy, and Joost Verhaagen. Developing a potentially immunologically-inert tetracycline regulatable viral vector for gene therapy in the peripheral nerve. Gene ther. (2014)
  • Ilary Allodi, Vasil Mecollari, Francisco González-Pérez, Ruben Eggers, Stefan Hoyng, Joost Verhaagen, Xavier Navarro, Esther Udina. Schwann cells transduced with a lentiviral vector encoding Fgf-2 promote motor neuron regeneration following sciatic nerve injury. Glia (2014)
  • van der Kallen LR, Eggers R, Ehlert EM, Verhaagen J, Smit AB, van Kesteren RE Genetic deletion of the transcriptional repressor NFIL3 enhances axon growth in vitro but not axonal repair in vivo. PLoS One (2015)
  • Fagoe ND, Attwell CL, Eggers R, Tuinenbreijer L, Kouwenhoven D, Verhaagen J, Mason MR. Evaluation of five tests for the assessment of functional recovery following cervical or thoracic dorsal column transection in the rat. Plos One (2016)
  • Eggers R, Tannemaat MR, De Winter F, Malessy MJ, Verhaagen J. Clinical and Neurobiological advances in promoting regeneration of the ventral root avulsion lesion. Eur J. Neurosci (2016)