Preclinical modeling

The group “Preclinical Modeling” headed by Dr. Marc Zuckermann, is part of Prof. Stefan Pfister’s division of “Pediatric Neurooncology” and focusses on establishing and utilizing in vivo tumor models for pediatric high-grade glioma.

We are using somatic gene delivery, most often in utero electroporation, to induce selected genetic aberrations orthotopically. Thereby, we are able to rapidly validate different combinations of candidate hits that have been identified in patient samples. Tumors derived from this approach are allografted, providing allogeneic and immunocompetent models.

Established allografts together with PDX models of collaborating groups are utilized to investigate biological questions and to conduct preclinical experiments with innovative treatment approaches. These include elaborate combination therapies, but also experimental treatments using adeno-associated virus-based gene therapy.



Spotlight - AG Zuckermann

Combining c-MET inhibition with radiation is effective in MET-fusion driven high-grade glioma

By investigating the cellular basis for capmatinib’s synergistic efficacy with RT, we found that the compound increases the amount and persistence of DNA double strand breaks induced by radiation.



Experimental therapy

Besides analyzing the efficacy of new and promising inhibitors in vivo, we are investigating an experimental therapy approach. Within this project, we are combining selected adeno-associated virus (AAV) variants with oncogene-specific CRISPR-nucleases to treat orthotopic in vivo models. We could identify novel tumor-specific AAV variants as well as oncogene-specific CRISPR-nucleases and are currently combining most promising candidates to evaluate their antitumor efficacy.

Overcoming resistance

In clinical trials, single agent modalities against various targets have displayed potent initial response, yet acquired resistance and tumor relapse is often inevitable. This holds true for many preclinical studies, also when using promising, modern inhibitors. Thus, we are currently aiming at generating resistant tumors in vivo in order to analyze the underlying resistance mechanisms. These efforts will not only provide valuable insight into tumor evolution under treatment but also inform future combinatorial therapy approaches.

Combination therapies

One recently emerged focus of the group is the combination of targeted treatment with radiotherapy (RT). We identified that combining MET inhibition with radiation is highly effective for the treatment of MET-driven pediatric high-grade glioma (pHGG) in multiple preclinical models, greatly outperforming single therapies. We are currently expanding this concept to further pHGG entities.



Sigaud, R. *, L. Rösch, C. Gatzweiler*, J. Benzel*, L. von Soosten*, H. Peterziel, F. Selt, S. Najafi, S. Ayhan, X. F. Gerloff, N. Hofmann, I. Büdenbender, L. Schmitt, K. I. Foerster, J. Burhenne, W. E. Haefeli, A. Korshunov, F. Sahm, C. M. van Tilburg, D. T. W. Jones, S. M. Pfister, D. Knoerzer, B. L. Kreider, M. Sauter*, K. W. Pajtler*, M. Zuckermann*, I. Oehme*, O. Witt*, and T. Milde*. 'The First-in-Class Erk Inhibitor Ulixertinib Shows Promising Activity in Mapk-Driven Pediatric Low-Grade Glioma Models. ' Neuro Oncol, 10: 1093.


Ernst, K., K. Okonechnikov, J. Bageritz, J. P. Mallm, S.M. Pfister, M. Zuckermann*, and D. T. W. Jones*. 'Establishment of a simplified preparation method for single-nucleus RNA-sequencing and its application to long-term frozen tumor tissues', bioRxiv 2020.10.23.351809.


Zuckermann, M., M. Hlevnjak, H. Yazdanparast, M. Zapatka, D. T. W. Jones, P. Lichter, and J. Gronych.


Zuckermann, M., V. Hovestadt, C. B. Knobbe-Thomsen, M. Zapatka, P. A. Northcott, K. Schramm, J. Belic, D. T. Jones, B. Tschida, B. Moriarity, D. Largaespada, M. F. Roussel, A. Korshunov, G. Reifenberger, S. M. Pfister, P. Lichter, D. Kawauchi, and J. Gronych. 'Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling', Nature Communications, 6: 7391.



Team members
  • Tuyu Zheng (PhD student, co-supervised with Kristian Patjler)
  • Kati Ernst (PhD student, co-supervised with David Jones)
  • Chun Ho Chan (PhD student)
  • Laura von Soosten (PhD student, co-supervised with David Jones)
  • Nina Hofmann (technician)
  • Alessia Cais (PhD student)
  • Marta Cook (MD student)
  • Eric Konrath (animal caretaker)
  • Chiara Lukasch (technical assistant, co-supervised with Lena Kutscher)

Dr. Marc Zuckermann

Group leader "Preclinical modeling"

Postal address:
Hopp Children's Cancer Center Heidelberg
Im Neuenheimer Feld 580
D-69120 Heidelberg