Rob Hoeben

Vakgebied(en)

  • Professor
  • Virus and Stem cell biology

Introductie

Rob C. Hoeben, PhD, is professor of gene transfer (since 2000) at the Leiden University, and Head of the Virus and Stem Cell Biology lab of the Department of Molecular Cell Biology at the Leiden University Medical Centre, in Leiden, The Netherlands. He is a graduate in Biology from Utrecht University (1986) and obtained his PhD at Leiden University in 1991. He performed postdoctoral research on the use of adenovirus and retrovirus vectors for treatment of liver disorders. He has been one of the first to document synthesis of functional factor VIII in primary human cells after retroviral gene transfer, he revealed the position-dependent inactivation of retrovirus vectors in fibroblasts, and documented the hepatotoxicity of the HSVtk/GCV system in the liver and the involvement of mitochondria therein. The ‘911’ helper cell line was developed for research-grade production of adenoviral vectors and, in collaboration with scientists at Crucell BV (Leiden) he developed the PER.C6 cell line and the associated virus-production platform. With Prof. Huizinga (Rheumatology) and Prof. Nelissen (Orthopaedic Surgery), were used he initiated a Phase I clinical study ‘Gene Therapy n Aseptic Prosthetic Replacement Loosening’ in which PER.C6-produced adenoviruses were used. He collaborates with Prof. Verhaagen for evaluating the use of immuno-stealth genes for gene therapy in the nervous system.

He is inventor of eleven US and one European patent, covering PER.C6 and associated technology. He is on the board of the Dutch Society of Gene Therapy, and Member of COGEM (Committee on Genetic Modification), which advises the Minister of Infrastructure and the Environment on the use of Genetically Modified Organisms. Prof. Hoeben published more than 115 papers in international peer-reviewed journals.

Current research interests include:

  1. Developing of tumour-targeted viruses for cancer therapy;
  2. Evaluating of viral immune evasion strategies for use in experimental gene therapy;
  3. Generating of insulin-producing cells from human mesenchymal stem cells;
  4. Developing lentivirus-derived vectors as platform-technology.

Selected recent publications (15)

  1. Ilett, E.J., Bárcena, M., Errington-Mais, F., Griffin, S., Harrington, K., Pandha, H., Coffey, M., Selby, P.J., Limpens, R.W., Mommaas, M., Hoeben, R.C., Vile, R.G.,  Melcher, A.A. (2011) Internalization of oncolytic reovirus by human dendritic cell carriers protects the virus from neutralization. Clin. Cancer Res. 17:2767-2776.
  2. Uil, T.G., Vellinga, J., De Vrij,J., Van den Hengel, S.K., Rabelink, M.J.W.E., Cramer, S.J., Eekels, J.J.M., Ariyurek, Y., van Galen, M., Hoeben, R.C. (2011) Directed adenovirus evolution using engineered mutator viral polymerases Nucl. Acids Res.  39(5): e30
  3. De Vrij, J., Willemsen, R.A., Lindholm. L., Hoeben, R.C. 2010 Adenovirus-derived vectors for prostate cancer gene therapy. Human Gene Ther. 21:795-805.
  4. Carlotti, F., Zaldumbide, A., Loomans, C.J., Van Rossenberg, E., Engelse, M., De Koning, E.J., Hoeben, R.C. 2010  Isolated human islets contain a distinct population of mesenchymal stem cells. Islets 2: 164-173.
  5. Wang, X., Herr, R.A., Rabelink, M., Hoeben, R.C., Wiertz, E.J., Hansen, TH. 2009 Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates. J. Cell Biol.187: 655–668.
  6. Chadt, A., Leicht, K., Deshmukh, A., Jiang, L.Q., Scherneck, S., Bernhardt, U., Dreja, T., Vogel, H., Schmolz, K., Kluge, R., Zierath, J.R., Hultschig, C., Hoeben, R.C., Schürmann, A., Joost, H.G., Al-Hasani, H. 2008 A mutation in the positional candidate gene Tbc1d1 in the SJL mouse strain confers leanness and protects from high-fat diet induced obesity. Nat. Genet. 40:1354-1359.
  7. Van den Wollenberg, D.J.M., Van den Hengel, S.K., Dautzenberg, I.J.C., Cramer, S.J., Kranenburg, O., Hoeben, R.C. 2008 A strategy for genetic modification of the spike-encoding segment of human reovirus T3D for reovirus targeting. Gene Ther. 15:1567–1578.
  8. De Poorter, J.J., Hoeben, R.C., Obermann, W.R., Huizinga, T.W., Nelissen, R.G. 2008 Gene therapy for the treatment of hip prosthesis loosening: adverse events in a  phase 1 clinical study. Hum. Gene. Ther. 19: 1029-1038.
  9. Eggers, R., Hendriks, W.T., Tannemaat, M.R., Van Heerikhuize, J.J., Pool, C.W., Carlstedt, T.P., Zaldumbide, A., Hoeben, R.C., Boer, G.J., Verhaagen J. 2008 Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots. Mol. Cell. Neurosci. 39:105-117.
  10. de Vrij, J., T. G. Uil, S. K. van den Hengel, S. J. Cramer, D. Koppers-Lalic, M. C. Verweij, E. J. Wiertz, J. Vellinga, R. A. Willemsen, and R. C. Hoeben. 2008. Adenovirus targeting to HLA-A1/MAGE-A1-positive tumor cells by fusing a single-chain T-cell receptor with minor capsid protein IX. Gene Ther. 15:978-989.
  11. de Poorter, J. J., R. C. Hoeben, S. Hogendoorn, V. Mautner, J. Ellis, W. R. Obermann, T. W. Huizinga, and R. G. Nelissen. 2008. Gene therapy and cement injection for restabilization of loosened hip prostheses. Hum. Gene Ther. 19:83-95.
  12. Zaldumbide, A., M. Ossevoort, E. J. Wiertz, and R. C. Hoeben. 2007. In cis inhibition of antigen processing by the latency-associated nuclear antigen I of Kaposi sarcoma herpes virus. Mol. Immunol. 44:1352-1360.
  13. Smakman, N., D. J. van den Wollenberg, S. G. Elias, T. Sasazuki, S. Shirasawa, R. C. Hoeben, R. Borel, I, and O. Kranenburg. 2006. KRAS(D13) promotes apoptosis of human colorectal tumor cells by ReovirusT3D and oxaliplatin but not by tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res. 66:5403-5408.
  14. Vellinga, J., M. J. Rabelink, S. J. Cramer, D. J. van den Wollenberg, M. H. Van der, K. N. Leppard, F. J. Fallaux, and R. C. Hoeben. 2004. Spacers increase the accessibility of peptide ligands linked to the carboxyl terminus of adenovirus minor capsid protein IX. J. Virol. 78:3470-3479.
  15. Carlotti, F., M. Bazuine, T. Kekarainen, J. Seppen, P. Pognonec, J. A. Maassen, and R. C. Hoeben. 2004. Lentiviral vectors efficiently transduce quiescent mature 3T3-L1 adipocytes. Mol. Ther. 9:209-217.

Granted patents

  1. Fallaux, F.J., Hoeben, R.C., Van der Eb, A.J., Bout, A., Valerio, D. (1999) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 5,994,128
  2. Bout, A., Hoeben, R.C. (2000) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 6,033,908
  3. Hoeben,  R.C., Bout, A. (2001) Method for intracellular DNA amplification. US patent 6,238,893
  4. Fallaux, F.J., Hoeben, R.C., Bout, A., Valerio, D., Van der Eb, A.J., Schouten, G. (2001) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 6,265,212
  5. Fallaux, F.J., Hoeben, R.C., Van der Eb, A.J., Bout, A., Valerio, D. (2001) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 6,306,652
  6. Fallaux, F.J., Hoeben, R.C., Bout, A., Valerio, D., Van der Eb, A.J., Schouten, G.J. (2002) Means and methods for nucleic acid delivery vehicle design and nucleic acid transfer. US patent 6,395,519
  7. Fallaux, F.J., Hoeben, R.C., Van der Eb, A.J., Bout, A., Valerio, D. (2003) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 6,602,706
  8. Fallaux, F.J., Hoeben, R.C., Bout, A., Valerio, D., Van der Eb, A.J. (2004) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 6,692,966
  9. Fallaux, F.J., Hoeben, R.C., Van der Eb, A.J., Bout, A.,  Valerio, D. (2004) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 6,783,980
  10. Fallaux, F.J., Hoeben, R.C., Bout, A., Valerio, D., Van der Eb, A.J. (2004) Packaging systems for human recombinant adenovirus to be used in gene therapy. European patent 0833934
  11. Fallaux, F.J., Hoeben, R.C., Van der Eb, A.J., Bout, A.,  Valerio, D. (2006) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 7,052,881 
  12. Fallaux, F.J., Hoeben, R.C., Van der Eb, A.J., Bout, A.,  Valerio, D. (2006) Packaging systems for human recombinant adenovirus to be used in gene therapy. US patent 7,105,346
  13. Huizinga, T.W.J., Hoeben, R.C., Nelissen, R.G.H.H., Mountain, A. (2010) Enzyme-prodrug therapy for prosthetic joint repair. European patent 1725267
  14. Huizinga, T.W.J., Hoeben, R.C., Nelissen, R.G.H.H., Mountain, A. (2010) Enzyme-prodrug therapy for prosthetic joint repair. US patent  7,674,454


Contactgegevens

Leids Universitair Medisch Centrum
Gebouw 2
Kamer T-02-056

Einthovenweg 20
2333 ZC Leiden
Tel: 071 5269241

Postzone S-1-P
Postbus 9600
2300 RC Leiden

E-mail: r.c.hoeben@lumc.nl