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Marlinde van den Boogaard

Postdoc
Marlinde van den Boogaard

Target identification and validation in neuroblastoma

Marlinde leads the target validation pipeline in our group. A highly efficient pipeline covering the full spectrum of targeted drug development is currently functional. The process starts with the validation of targets using high throughput analysis as Affymetrix mRNA profiling, RNAseq, Whole Genome Sequencing and single cell analysis. We are now building a dataset of over 500 neuroblastoma tumors for which WGS and RNA profiling data is available. We will perform integrative analysis on these samples that will allow identification of new driving events and relate genomic events to clinical subgroups within neuroblastoma. Potential new target genes are subsequently validated in cell line systems using a variety of molecular genetic manipulation techniques. The most promising target genes are then further validated using small molecule inhibitors in vitro and in vivo. Several new models are developed to consolidate this process. Tumor organoids are used and new in vivo xenograft and transgenic models are implemented. The current studies are in various stages of development and targets are MDM2, CDK4/6, CDKN2A, MEK pathway (RAS, NF1, PHOX2B, CIC), ATRX and MTH1 in neuroblastoma with the CtoA mutator phenotype.