Prof. Dr. rer. nat. Reinhold Schäfer

Senior Professor at the Charité Comprehensive Cancer Center (CCCC)

Molecular Tumor Biology

Charité - Universitätsmedizin Berlin

Email: reinhold.schaefer(at)charite.de

Phone: 030 450 564 640

University Education

1976 Ph.D., Universität Bonn

Professional Experience (selection)

1976-1978 Postdoctoral fellow at the Division of Molecular Genetics, Max Planck Institute for Experimental Medicine (MPI), Göttingen
1978-1985 Postdoctoral fellow at the Institute of Cell Biology (Tumor Research), West German Cancer Center, Universität Essen
1985-1988 Principal investigator, Ludwig Institute for Cancer Research, Bern, Switzerland
1988-1996 Head, Division of Cancer Research, Department of Pathology, University Hospital Zürich, Switzerland
1996-2008 Professor of Molecular Tumor Pathology, Institute of Pathology, Charité
2009-2018 Deputy director (Translational Research), CCCC
2019- Senior Professor at CCCC

Most important Awards, Grants or Scientific Achievements

1988 Swiss Cancer Award (Robert-Wenner-Preis), Swiss Cancer Society
2001 Award of the Stifterverband für die deutsche Wissenschaft

Scientific Scope

General interest:

Understanding the global genome-wide effects of RAS oncogenes on cellular transformation, tumor formation and therapy resistance.

Specific research themes:

1) Investigation of alterations of the genetic program mediated by mutant RAS genes in generic cell culture models, patient tumor-derived organoid cultures by means of multi-omics approaches.

2) Identification of specific vulnerabilities of cells expressing RAS mutants and exploiting their relevance for targeted therapy.

3) Identification of small molecular weight compounds able to block the activity of RAS pathway-responsive transcription factors in solid tumor models (colorectal cancer, pancreatic cancer, melanoma).

4) Characterization of transcription factor networks that execute transformed properties and phenotypes mediated by chronic activation of the RAS signaling system.

5) Translation of preclinical evidence obtained in model systems into early clinical trials.

Network model of hierarchical and regulatory interactions among KRAS-responsive transcription factors and cytoplasmic signaling. Arrows point at direct activating interactions between network components. The markings +/- placed at the top of a protein symbol represent activation or inhibition of transcription factors by cytoplasmic signaling; the markings placed at the bottom of a sprotein symbol imply stimulation or inhibition of signaling activity (kinase phosphorylation) by downstream transcription factors. From: Stelniec-Klotz et al. Molecular Systems Biology, 2012

Future directions

Validation of drug response predictions obtained in generic models in patient tumor-derived organoid cultures (PDO) and xenotransplants (PDX). Analysis of the downstream effects of targeted intervention at the systems level. Provision of a mechanistic understanding of drug sensitivities and resistance.

Selected references

Kuhn, N., Klinger, B., Uhlitz, F., Sieber, A., Rivera, M., Klotz-Noack, K., Fichtner, I., Hoffmann, J., Blüthgen, N., Falk, C., Sers, C., Schäfer, R. (2020) "Mutation-specific effects of NRAS oncogenes in colorectal cancer cells." Adv Biol Regul.2020 Dec 31:100778. doi: 10.1016/j.jbior.2020.100778.
Klotz-Noack, K., Klinger, B., Rivera, M., Bublitz, N., Uhlitz, F., Riemer, P., Lüthen, M., Sell, T., Kasack, K., Gastl, B., Ispasanie, S.S.S., Simon, T., Janssen, N., Schwab, M., Zuber, J., Horst, D., Blüthgen, N., Schäfer, R., Morkel, M., Sers, C. (2020) "SFPQ Depletion Is Synthetically Lethal with BRAFV600E in Colorectal Cancer Cells." Cell Rep. Sep 22;32(12):108184. doi: 10.1016/j.celrep.2020.108184.
Gastl, B., Klotz-Noack, K., Klinger, B., Ispasanie, S., Salib, K.H.F., Zuber, J., Mamlouk, S., Bublitz, N., Blüthgen, N., Horst, D., Morkel, M., Schäfer, R., Sers, C. (2020) "Reduced replication origin licensing selectively kills KRAS-mutant colorectal cancer cells via mitotic catastrophe." Cell Death Dis. Jul 1;11(7):499. doi: 10.1038/s41419-020-2704-9.
Schumacher, D., Andrieux, G., Boehnke, K., Keil, M., Silvestri, A., Silvestrov, M., Keilholz, U., Haybaeck, J., Erdmann, G., Sachse, C., Templin, M., Hoffmann, J., Boerries, M., Schäfer, R., Regenbrecht, C.R.A. (2019) "Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures." PLoS Genet. Mar 29;15(3):e1008076. doi: 10.1371/journal.pgen.1008076. eCollection 2019 Mar. Erratum in: PLoS Genet. 2019 May 29;15(5):e1008183.
Regan, J.L., Schumacher, D., Staudte, S., Steffen, S., Johannes Haybaeck, J., Keilholz, U., Schweiger, C., Golob-Schwarz, N., Mumberg, D., Henderson, D., Lehrach, H., Regenbrecht, C.R.A.R., Schäfer, R., Lange, M. (2017) "Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells."Cell Reports 21, 2813–2828.