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PhD H.A.M. Geerts

Position
Support Staff
Main activities
Research
Specialisation
Molecular genetics and cell biology on the pediatric tumor neuroblastoma
Focus of research

 Oncogenic pathways in the pediatric tumor neuroblastoma, with a focus on early developmental programs

Key publications
  • Revet Ingrid, Huizenga Gerda, Koster Jan, Volckmann Richard, van Sluis Peter, Versteeg Rogier, Geerts Dirk MSX1 induces the Wnt pathway antagonist genes DKK1, DKK2, DKK3, and SFRP1 in neuroblastoma cells, but does not block Wnt3 and Wnt5A signalling to DVL3 Cancer letters 2010;289 (2):195-207 [PubMed]
  • Molenaar Jan J., Ebus Marli E., Geerts Dirk, Koster Jan, Lamers Fieke, Valentijn Linda J., Westerhout Ellen M., Versteeg Rogier, Caron Huib N. Inactivation of CDK2 is synthetically lethal to MYCN over-expressing cancer cells Proceedings of the National Academy of Sciences of the United States of America 2009;106 (31):12968-12973 [PubMed]
  • Xu Bei, Geerts Dirk, Qian Kun, Zhang Hanwang, Zhu Guijin Myeloid ecotropic viral integration site 1 (MEIS) 1 involvement in embryonic implantation Human reproduction (Oxford, England) 2008;23 (6):1394-1406 [PubMed]
  • Revet Ingrid, Huizenga Gerda, Chan Alvin, Koster Jan, Volckmann Richard, van Sluis Peter, Øra Ingrid, Versteeg Rogier, Geerts Dirk The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma Experimental cell research 2008;314 (4):707-719 [PubMed]
  • Geerts Dirk, Wallick Christopher J., Koomoa Dana-Lynn T., Koster Jan, Versteeg Rogier, Go Ramon Christopher V., Bachmann André S. Expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in neuroblastoma: correlation with clinical features, cellular localization, and cerulenin-mediated apoptosis regulation Clinical cancer research 2007;13 (21):6312-6319 [PubMed]
All Publications
Research programmes

PhD H.A.M. Geerts (Developmental genes in neuroblastoma pathogenesis)

 Neuroblastoma is an aggressive childhood tumor, which accounts for 15% of all childhood cancer deaths. Survival rates for neuroblastoma have seen only limited progress over the last decades. We aim to apply tumor-driven and fundamental research of neuroblastoma to identify and validate targeted therapy with novel drugs. We study neuroblastoma by systematic high throughput analysis of tumor series, to identify aberrant genes and expression patterns associated with survival and clinical and molecular parameters. The function of candidate genes is studied by induction of cDNA and shRNA expression in neuroblastoma cell lines. Downstream pathways of genes inducing strong phenotypes are identified by mRNA profiling of time series after induction. Bioinformatic tools integrate the clinical data, the data from the tumor series, and the experimental data and allow the prioritization of genes that are relevant for tumor biology in vivo. This way we work towards an understanding of the multiple pathways that together drive neuroblastoma cell proliferation and are aberrantly functioning in the distinct clinical sub-sets of neuroblastoma. Small molecule drugs are employed to inhibit identified target genes, in the search for synthetic lethal genes and new drug combinations. Two interesting pathways I study are a differentiation route (1) and the NF-kB pathway (2). See