foto

Dr. W.J. van Nes

Position
Postdoc
Main activities
Research
Specialisation
Molecular biology
Focus of research

Notch signaling in neuroblastoma stem cells

Neuroblastoma is a childhood tumour from the peripheral sympathetic nervous system. Aggressive stages are widely metastatic to the bone and bone marrow, frequently relapse due to therapy resistance and patients are faced with an extremely poor prognosis.

We are studying the mechanisms of migration and invasion of human neuroblastoma cells in vitro and in vivo. Our data reveals that Notch signaling exerts a master switch in cell migration, as identified by strong phenotypic alterations in cell morphology and -migration accompanied by the induction of large numbers of genes involved in cell motility. 

Furthermore Notch signaling is prominently activated in a subset of stem-like tumour-initiating-cells. We have developed sphere-forming assays and selected subsets of cells that are currently evaluated for tumorigenic potential in vivo and analyzed for transcriptional activation of pathways involved in stem cell maintenance.

We aim at further elucidating the in vivo contribution of the Notch pathway in metastasis of stem-like neuroblastoma cells. Ultimately, understanding the molecular mechanisms that maintain the undifferentiated and metastatic states will guide the route to new therapeutic avenues for neuroblastoma patients.

Team:

Johan van Nes, PhD, group leader

Nurdan Akogul, Technician

Marloes Broekmans, Technician

Laurel Tate-Beya, PhD-student

Tim van Groningen, PhD-student

Key publications
  • van Nes J, de Graaff W, Lebrin F, Gerhard M, Beck F, Deschamps J, The Cdx4 mutation affects axial development and reveals an essential role of Cdx genes in the ontogenesis of the placental labyrinth in mice. DEVELOPMENT 2006;133 (3):419-428 [PubMed]
  • Young T, Rowland JE, van de Ven C, Bialecka M, Novoa A, Carapuco M, van Nes J, de Graaff W, Duluc I, Freund JN, Beck F, Mallo M, Deschamps J, Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos. DEV CELL 2009;17 (4):516-526 [PubMed]
  • Deschamps J, van Nes J, Developmental regulation of the Hox genes during axial morphogenesis in the mouse. DEVELOPMENT 2005;132 (13):2931-2942 [PubMed]
All Publications
Research programmes

Prof. dr. R. Versteeg (Regulatory networks in cancer)