Group "Preclinical research"

Research interests of the Embryonal Brain Tumor and Preclinical Research Group, headed by Dr. Marcel Kool (PhD), which is also part of the DKFZ divison "Pediatric Neurooncology" (headed by Prof. Dr. Stefan Pfister), are the (epi)genomic analyses of medulloblastomas, ependymomas, ATRTs, ETMRs and CNS-PNETs. This includes the recently discovered new molecular entities CNS-NB, CNS-EFT-CIC, HGNET-BCOR, and HGNET-MN1. For our analyses we use high-throughput and up-to-date DNA- and (mi)RNA-sequencing, DNA methylation profiling, RNA profiling and ChIP-sequencing.

Over the years we got quite a good idea of what is driving most of these less frequent but often aggressive brain tumors, but there is still much to learn from further (epi)genomic analyses as the main drivers and/or therapeutic targets are not clearly defined in all tumors. The aim is, therefore, to characterize these in a better way, identify clinically relevant and distinct molecular subgroups and the genes and pathways that drive them, and, most importantly, develop proper human and mouse model systems reflecting the different diseases and the inter- and intra-tumor heterogeneity. Additionally, we strive to find novel candidates for rational targeted therapies. We aim to translate knowledge obtained from these (epi)genomic studies into novel strategies for most optimal treatments of patients.

Novel drug targets, often in combination with established cytotoxic drugs and/or chemotherapy, are being investigated using the model systems (cell lines, patient-derived orthotopic xenografts [PDX], and organoid cultures). The current focus of the group is on targeting MYC(N)-driven brain tumors, SHH-driven medulloblastomas, PFA and RELA-ependymomas, and ETMR tumors, using a wide spectrum of drugs.

Main research aspects

In collaboration with several international partners (James Olson, Xiao-Nan Li, Robert Wechsler-Reya and others) we have built up a large repertoire of 100-150 different orthotopic brain tumor PDX models, which cover the main pediatric brain tumor entities and their respective molecular subgroups and which are all being characterized at a molecular level by us at the DKFZ. All models and matching molecular data will be made available for the community through easy-accessible websites, such as R2. The group is also involved in the molecular characterization of an even larger (~400) series of PDX models across many different high risk pediatric cancers as part of the IMI-2 / ITCC-P4 consortium. In collaboration with Hans Clevers and Marc van de Wetering at the Princess Maxima Center in Utrecht, we also try to grow several of these PDX models as organoid cultures. All these different model systems will be used for further preclinical studies, including high-throughput drug screens, shRNA screens, and CRISPR/Cas9 screens, to find new and better drug targets and for understanding primary and acquired therapy-related resistance mechanisms.


  • Marcel Kool, PhD (Group Leader, also deputy of the division Pediatric Neurooncology)
  • Pascal Johann, MD (Physician Scientist)
  • Sjoerd van Rijn (Postdoc)
  • Daniel Senfter (PostDoc)
  • Aniello Federico, PhD (PostDoc)
  • Sebastian Brabetz (PhD student)
  • Sander Lambo (PhD student)
  • Jens-Martin Hübner (PhD student)
  • Anke Heit (PhD student)
  • Sonja Krausert (PhD student)
  • Monika Mauermann (Technician)
  • Norman Mack (Technician)
  • Benjamin Schwalm (Technician)


  • Fabian Kratochwil (Technician)
  • Christin Schmidt (PhD student and Postdoc)
  • Kristian Pajtler (Physician Scientist, currently PI of independent group within the division "Early cancer diagnostics & reverse translation")
  • Hendrik Witt, MD (Physician Scientist)

Marcel Kool, PhD

Group leader "Preclinical research"

Postal address:
Hopp Children's Cancer Center Heidelberg
Im Neuenheimer Feld 280
D-69120 Heidelberg

Selected publications

1. Mack SC, Pajtler KW, Chavez L, et al. Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling. Nature 2018;553:101-105.

2. Sturm D, Orr BA, Toprak UH, et al. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell 2016;164:1060-72.

3. Johann PD, Erkek S, Zapatka M, et al. Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes. Cancer Cell 2016;29:379-93.

4. Pajtler KW, Witt H, Sill M, et al. Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell 2015;27:728-43.

5. Kool M, Jones DT, Jäger N, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 2014;25:393-405.