Contact

 

Dr. Björn Tews
Phone: +49 6221 421570

E-mail: b.tews@dkfz.de

Identification and modulation ....

 

of molecular mechanisms governing brain tumor invasion.

Molecular Mechanisms of Tumor Invasion

DKFZ
 
 
 

Our group/department has:

  • proposed that epigenetic silencing of PRDX1 is frequent in 1p/19q-deleted gliomas and likely contributes to radio- and chemosensitivity of these tumors (Dittmann* and Danner* et al., Oncogene 2012).
  • identified the GPCR sphingosine 1-phosphate receptor 2 (S1PR2) as a Nogo-A-Δ20-specific receptor. Nogo-A is a potent myelin-derived inhibitor of cell spreading and neurite outgrowth in the central nervous system. We provide a novel biological concept of multi-ligand GPCR signaling in which this sphingolipid-activated GPCR is also bound and activated by a high molecular weight membrane protein, Nogo-A, in trans. To our knowledge, this is the first example of a rhodopsin-like GPCR that can bind to a mammalian membrane protein (Kempf* and Tews* et al., PLoS Biol 2013, WO2012164103).
  • generated a novel transgenic rat model using RNAi and used it to study the role of the membrane protein Nogo-A in synaptic plasticity and cognition. The resulting significant increase in long-term potentiation in both hippocampus and motor cortex indicates a repressor function of Nogo-A in synaptic plasticity. Furthermore, the transgenic rats exhibited prominent schizophrenia-like behavioral phenotypes (Tews* and Schönig* et al., PNAS 2013).

2010 – 2013

  • The sphingolipid receptor S1PR2 is a receptor for Nogo-A repressing synaptic plasticity (Kempf A*, Tews B*, Arzt ME, Weinmann O, Obermair FJ, Pernet V, Zagrebelsky M, Delekate A, Iobbi C, Zemmar A, Ristic Z, Gullo M, Spies P, Dodd D, Gygax D, Korte M, Schwab ME, PLoS Biol 2013).
  • Synthetic microRNA-mediated downregulation of Nogo-A in transgenic rats reveals its role as regulator of synaptic plasticity and cognitive function (Tews B*, Schönig K*, Arzt ME, Clementi S, Rioult-Pedotti MS, Zemmar A, Berger SM, Schneider M, Enkel T, Weinmann O, Kasper H, Schwab ME, Bartsch D, PNAS 2013).
  • Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro (Dittmann LM*, Danner A*, Gronych J, Wolter M, Stühler K, Grzendowski M, Becker N, Bageritz J, Goidts V, Toedt G, Felsberg J, Sabel MC, Barbus S, Reifenberger G, Lichter P, Tews B, Oncogene 2012).
  • Differential retinoic acid signaling in tumors of long- and short-term glioblastoma survivors (Barbus S*, Tews B*, Karra D, Hahn M, Radlwimmer B, Delhomme N, Hartmann C, Felsberg J, Krex D, Schackert G, Martinez R, Reifenberger G, Lichter P, J Natl Cancer Inst 2011).
  • Molecular signatures classify astrocytic gliomas by IDH1 mutation status (Toedt G*, Barbus S*, Wolter M, Felsberg J, Tews B, Blond F, Sabel MC, Hofmann S, Becker N, Hartmann C, Ohgaki H, von Deimling A, Wiestler OD, Hahn M, Lichter P, Reifenberger G, Radlwimmer B, Int J Cancer 2011).
  • 2011: CellNetworks Cluster of Excellence & DKFZ
  • 2006: Award of excellence for the dissertation, Ruprecht Karls-University Heidelberg
  • 2002: Award of excellence for the diploma thesis, Justus Liebig-University Giessen