PhD H.A.M. Geerts

All Publications

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