Prof. Dr. rer. nat. Ulrike Stein

Translational Oncology of Solid Tumors
Charité - Universitätsmedizin Berlin
Max-Delbrück Center for Molecular Medicine
Robert-Rössle-Str. 10
13092 Berlin
Tel: +49 30 9406 3432

E-Mail: ustein@mdc-berlin.de
https://www.mdc-berlin.de/stein

University Education

  • 1979-1984 Martin-Luther University Halle, Diploma in Biochemstry
  • 1987-1991 Academy for Clinical Education, Berlin, Graduation in Medicinal Biochemistry 

Professional Experience (selection)

  • 1984-1991 PhD, Humboldt-University Berlin
  • 1991-1993  Post-Doc MDC Berlin
  • 1994-1995 Post-Doc National Cancer Institute, Frederick, MD, USA (Alumni one month research stays 1996, 1997, 1998, 2001, 2003, 2007, 2011)
  • 1996-2000 Group leader MDC
  • 2001-2006  Group leader Robert-Rössle-Clinic, Berlin
  • 2003 Habilitation, Charité University Medicine, Berlin
  • 2007- Group leader ECRC, Berlin
  • 2009- Professorship, Charité University Medicine, Berlin

Research Fields

  • i) Molecular and Translational Oncology 
  • ii) Metastasis and Biomarkers: Prognosis and Prediction
  • iii) Chemoprevention and Therapeutic Intervention of Tumor Progression and Metastasis

Scientific Scope

Background:

Colon cancer is one of the most frequent causes for cancer death worldwide. Patients with non-metastatic, local tumors have a 5-year-survival of about 90%, but less than 10%, when distant metastases have formed. Metastasis is the most lethal attribute of colon cancer and still represents the major problem in cancer treatment. Molecular, biological, translational, and clinical aspects of cancer metastasis are the main focus of our group.

Diagnostic, prognostic and predictive biomarkers for metastasis:

For instance, we identified a new gene, MACC1, which turned out to be causal, but also prognostic for formation and predictive for treatment of cancer metastases. MACC1 is a master regulator of the HGF/Met pathway, but also of further metastasis genes and pathways. We identified metastasis inducers such as S100A4 as targets of the Wnt/β-catenin pathway, and unveiled its causal and prognostic role for metastasis. Both pathways are most decisive for tumorigenesis and metastasis. The clinical use of metastasis biomarkers is based on single or combinatorial approaches including mutation, expression, and functional patterns. We established assays for monitoring metastasis genes in patients’ blood, which is of importance for clinical trials aiming at chemoprevention of metastasis.

Prevention and inhibition of metastasis:

Therapeutic translation is approached by a variety of strategies. For instance, we identified inhibitors via high throughput screening, employing libraries with 17.000 compounds to restrict the transcriptional activity of metastasis inducers. Inhibitors were evaluated using standardized mouse models for in vivo bioluminescence imaging. Identified FDA-approved drugs offer therapeutic potential for patients at high risk for metastasis and ensure the rapid initiation of clinical trials. Post-transcriptional silencing of metastasis genes with RNAi was performed intratumorally (jet-injection) or systemically (tail vein injection), leading to chemosensitization and metastasis inhibition in mouse models. Our structure-based interventions aim at the domain architecture of metastasis proteins. The identification of e.g. protein-protein-interaction domains provide the basis for tailored structure-based inhibitory small molecules.

 

Most important Awards, Grants or Scientific Achievements

  • 1994-1995 Feodor-Lynen-fellowship, Alexander von Humboldt foundation / Fogarty International Center, Bethesda, MD, USA
  • 2005 Award, Epithelial Mesenchymal Transition Conference, Vancouver, BC, Canada
  • 2009 Wissenschaftspreis (preclinical/translational part), AIO of the German Cancer Society
  • 2010 Award of the Berlin-Brandenburg Academy of Science, Monika Kutzner foundation
  • 2011 Award, 16. World Congress on Advances in Oncology, Rhode, Greece

Selected References

  • Stein, U, Arlt, F, Walther, W, Smith, J, Waldman, T, Harris, ED, Mertins, SD, Heizmann, CW, Allard, D, Birchmeier, W, Schlag, PM, & Shoemaker RH. (2006) The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer. Gastroenterology, 131,1486-1500.
  • Stein, U, Walther, W, Arlt, F, Schwabe, H, Smith, J, Fichtner, I, Birchmeier, W, & Schlag, PM. (2009) MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis. Nat Med, 15,59-67.
  • Stein, U, Smith, J, Walther, W, & Arlt, F. (2009) MACC1 controls Met – what a difference an Sp1 site makes. Cell Cycle, 8,2467-2469.
  • Stein, U, Dahlmann, M, & Walther, W. (2010) MACC1 – more than metastasis? Facts and predictions about a novel gene. J Mol Med, 88,11-18.
  • Sack, U, Walther, W, Scudiero, D, Selby, M, Aumann, J, Lemos, C, Fichtner, I, Schlag, PM, Shoemaker, RH, & Stein U. (2011) S100A4-induced cell motility and metastasis is restricted by the Wnt/β-catenin pathway inhibitor calcimycin in colon cancer cells. Mol Biol Cell, 22,3344-3354.
  • Stein, U, Arlt, F, Smith, J, Sack, U, Herrmann, P, Walther, W, Lemm, M, Fichtner, I, Shoemaker, RH, & Schlag PM. (2011) Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. Neoplasia, 13,131-144.
  • Sack, U, Walther, W, Scudiero, D, Selby, M, Kobelt, D, Lemm, M, Fichtner, I, & Schlag PM, Shoemaker RH, & Stein U. (2011) Novel effect of antihelminthic Niclosamide on S100A4-mediated metastatic progression in colon cancer. J Natl Cancer Inst, 103,1018-1036.
  • Pichorner, A, Sack, U, Kobelt, D, Kelch, I, Arlt, F, Smith, J, Walther, W, Schlag, PM, & Stein U. (2012) In vivo imaging of colorectal cancer growth and metastasis by targeting MACC1 with shRNA in xenografted mice. Clin Exp Metastasis, 29,573-583.
  • Dahlmann, M, Sack, U, Herrmann, P, Lemm, M, Fichtner, I, Schlag, PM, & Stein U. (2012) Systemic shRNA mediated knock down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation. Oncotarget, 3,783-797.
  • Schmid, F, Burock, S, Klockmeier, K, Schlag, PM, & Stein, U. (2012) SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer. Mol Cancer, 11:49. [Epub ahead of print]