Dr Kool studies the genomics and epigenomics of pediatric brain tumors and how to translate findings from these studies into novel therapies. More effective and less toxic therapies are highly needed as there are many types of childhood brain tumors for which the survival is still very poor or where survivors suffer from serious long-term side effects caused by their intensive therapies. In order to develop such new therapies, preclinical models, molecularly well-characterized, and representing the broad spectrum of different pediatric brain tumor entities and the inter-tumor heterogeneity within each of these entities are needed. These will be used to get a better understanding of tumor origin and biology and to find new ways how to target them.
The types of pediatric brain tumors that the Kool group is mostly focusing on are ependymomas (EPN) and embryonal brain tumors. The latter include medulloblastomas (MB), atypical / teratoid rhabdoid tumors (ATRT), embryonal tumors with multilayered rosettes (ETMR), and other tumor types previously called primitive neuroectodermal tumors of the central nervous system (CNS-PNETs). PI Marcel Kool is a world leading expert in the classification and molecular characterization of these types of tumors and has published several landmark papers for each of these different entities. Dr Kool leads two research groups, one at Princess Maxima Utrecht, The Netherlands and the other at the Hopp Children’s Cancer Center (KiTZ) in Heidelberg, Germany. Both groups are part of these same research program and focus on different aspects of ependymomas and embryonal brain tumors. The group in Heidelberg works on the genomic and epigenomic analyses of these types of tumors and how to translate (epi)genomic findings to the clinic using patient-derived xenograft (PDX) mouse models. They are also strongly involved in the ITCC-P4 consortium that aims to establish and characterize >400 PDX models of solid pediatric cancers and use these for high throughput in vivo preclinical studies. The group in Utrecht is modeling these tumors using organoid technology to better understand the biology of these tumors and to perform preclinical experiments.