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Emmy Dolman

  • Molenaar group
Emmy Dolman
Personalized models in neuroblastoma

  • Emmy leads the Personalized models research line. Our precision medicine program will be supported by personalized tumor models that can be used to test targeted compounds. First attempts to generate neuroblastoma organoids have shown promising results but culturing of sufficient cells took on average 4 months and the culturing procedures were only successful in 50% of the high-risk neuroblastoma. In order to optimize growth conditions for neuroblastoma organoids, we are currently systematically testing a repository of components of growth factors, pathway activating or inactivating components and various growth matrices and co-culture methods. The optimal conditions are selected by determining optimal growth and tumor take rates. In addition, we are performing single cell RNAseq on tumor biopsies to determine the heterogeneity of neuroblastoma tumors. We will compare this with single cell RNAseq analysis of organoids that are derived through various growth conditions. These organoids are now used for automatic testing of a large compound library using robotics in a semi high-throughput set-up. A large series of pediatric cancer cell lines has been tested using this pipeline to generate a reference dataset. We will also use the same pipeline to test non-malignant tissue organoids. High throughput compound testing will be prioritized for patient samples that are also tested in the iTHER pipeline. Thereby we can determine if the identified actionable events in a patient in the iTHER project indeed select for increased sensitivity for corresponding targeted compounds. In addition, we can identify potential therapeutic options for patients in which no actionable events were identified. Finally, we will use the organoid systems and the robotics system to test for optimal combination treatment options. These combination treatment options can be tested in in vivo models (PDX/GEMMS) that will be generated through an IMI2 funded program.