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 Division of Pediatric Neurooncology at DKFZ (headed by Prof. Dr. Stefan Pfister), are the (epi-)genetic analyses of medulloblastomas, ependymomas, ATRTs, ETMRs, and CNS-PNETs. These include the recently discovered new molecular entities CNS-NB-FOXR2 activated, 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.

Within the last few years, we have gotten a pretty good idea of what drives most of these less common but often aggressive brain tumors. However, we can still learn a lot with the help of further (epi-)genetic analysis. To do this, we are using cutting-edge technologies, including single-cell omics, for example, because the triggers and/or therapeutic targets are not known for all tumors.


Our goal is therefore to better characterize them, to identify clinically relevant and distinct molecular subgroups as well as the genes and signaling pathways driving them, and, most importantly, to develop suitable human and murine model systems through which the various diseases and interactions can be recapitulated and which reflect the heterogeneous situation within a tumor. In addition, we are committed to finding new candidates for targeted therapies. Our goal is to translate findings from these genomic studies into novel strategies for optimal treatment of patients.

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






Spotlight - AG Kool

ITCCP4: Preclinical lab models

We are currently working on creating a new Spotlight for you and therefore ask for a little patience. However, we are also part of the international research project ITCCP4: Preclinical Laboratory Models, for example. The overall goal of the initiative is to accelerate the development of new drugs for children with cancer and to develop new biomarkers.




Model platforms on pediatric brain tumors

In collaboration with several international partners (James Olson, Xiao-Nan Li, Robert Wechsler-Reya and others), we have built a large repertoire of 100-150 different orthotopic brain tumor PDX models covering the major pediatric brain tumor entities and corresponding molecular subsets that we at DKFZ are characterizing at the molecular level. All models and corresponding molecular data are made available to the community via easily accessible websites such as R2.

As part of the IMI-2 / ITCC-P4 consortium, our group is also involved in the molecular characterization of an even larger (~400) set of PDX models for many different high-risk pediatric cancers. In September 2019, Dr. Marcel Kool established a second research group at the Princess Máxima Center for Pediatric Oncology in Utrecht, The Netherlands, with the overall goal of fostering interactions and collaborations between the two pediatric cancer centers. The focus of research in this other group is on brain (tumor) organoids derived either from fresh tumor tissue or from embryonic or induced pluripotent stem cells. We use these organoids as preclinical model systems for preclinical studies, including high-throughput drug screens, shRNA screens, and CRISPR / Cas9 screens, to find new and better targets and to understand primary and acquired therapy-related resistance mechanisms (


Gojo J, Englinger B, Jiang L, et al. Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma. Cancer Cell 2020;38:44-59.

Lambo S, Gröbner S, Rausch T, et al. The molecular landscape of ETMR at diagnosis and relapse. Nature 2019;576:274-280.

Chun HE, Johann PD, Milne K et al. Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration. Cell Reports 2019;29:2338-2354.

Erkek S, Johann PD, Finetti MA, et al. Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation. Cancer Cell 2019;35:95-110.

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

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

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.

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.

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.

Team members
  • Dr. Marcel Kool (Group Leader & Deputy Department Head of the Division of Pediatric Neuro-oncology)
  • Dr. Pascal Johann, MD (Physician Scientist)
  • Dr. Daniel Senfter (PostDoc)
  • Dr. Aniello Federico (PostDoc)
  • Dr. Johannes Gojo (PostDoc)
  • Dr. Aylin Camgoz (PostDoc)
  • Dr. Sander Lambo (Postdoc)
  • Anke Heit (PhD student)
  • Sonja Krausert (PhD student)
  • Felix Schmitt-Hoffner (PhD student)
  • Anne Jenseit (PhD student)
  • Enrique Blanco Carmona (PhD student)
  • Monika Mauermann (Technical Assistant)
  • Norman Mack (Technical Assistant)
  • Benjamin Schwalm (Technical Assistant)
  • Annette Büllesbach (Medical PhD student)

Marcel Kool, PhD

Group leader "Preclinical research"

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