Prof. Dr. Thorsten Stiewe

Genomic stress: demise and resurrection of the guardian angel p53

Hazards from the environment or originating within our body constantly challenge the integrity of our DNA and cause genomic stress. As genomic stability is essential for health at the cellular, organismal or species level, our cells have developed coping mechanisms to deal with DNA damage. This is centrally coordinated by the p53 protein, which is therefore dubbed ‘guardian of the genome’. When p53 fails, this ultimately triggers cancer. It is therefore not surprising that p53 mutations are the most frequent alterations observed in cancer cells and that drugs which restore the anti-cancer activity of mutant p53 are considered a holy grail of tumor therapy. However, fixing a broken protein is pharmacologically far from trivial and no p53 mutant is like the other. I will present experimental insight from our lab into the complexity of the p53 mutome, discuss functional consequences and clinical implications of distinct p53 mutations, and highlight novel concepts for therapeutic p53 restoration.

Curriculum vitae

Date of Birth: 15.11.1970

University Education

2006                   Habilitation, Biochemistry and Molecular Biology, University of Würzburg

2004                   Approbation

2000                   Dr. med., University of Essen

1997                   State examination in Medicine, University of Essen

 

Employment and Positions

2015 – present   Director of the Institute of Molecular Oncology

2010 – present   Head of Genomics Core Facility, Philipps University Marburg

2010 – present   Professor of Molecular Oncology (W3), Philipps University Marburg

2007 – 2010       Professor of Molecular Oncology (W2), Philipps University Marburg

2002 – 2007       Junior Group Leader, Rudolf-Virchow-Center (DFG Research Center for Experimental Biomedicine), University of Würzburg

2000 – 2002       Post-doctoral fellow, Institute of Molecular Biology, West German Cancer Center, University of Essen

1997 – 2000       Graduate student, Institute of Molecular Biology, West German Cancer Center, University of Essen

 

Other Activities

2012 – present   Member of the Steering Committee of the Universities of Gießen and Marburg Lung Center (UGMLC), Coordinator of the section "Lung Cancer"

2011 – present   Member of the German Center for Lung Research (DZL)

2008 – 2013       Coordinator of the DFG Integrated Graduate School "Molecular Cancer Biology" (SFB/Transregio TR17)

2004 – 2013       Executive board member of the DFG Transregio TR17 "Ras-dependent pathways in human cancer"

 

Awards and Honours

2014                   Award for Research on Animal Welfare of the Federal State of Hesse

2010                   European Research Council Starting Grant

2007                   C.G. Schmidt Medal for Cancer Research

2002                   Junior Group Award by the DFG Research Center Würzburg

2002                   Wissenschaftspreis Medizin, University Essen

2001                   Forschungspreis Westdeutsches Tumorzentrum e.V.

 

Publications

http://www.ncbi.nlm.nih.gov/pubmed/?term=stiewe+t

 

Ten most important publications

 

  1. Timofeev O, Klimovich B, Schneikert J, Wanzel M, Pavlakis E, Noll J, Mutlu S, Elmshäuser S, Nist A, Mernberger M, Lamp B, Wenig U, Brobeil A, Gattenlöhner S, Köhler K, Stiewe T (2019). Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses. EMBO J, in press.

  2. Stiewe T, Haran TE (2018). How mutations shape p53 interactions with the genome to promote tumorigenesis and drug resistance. 38, 27-43. (review article)

  3. Vogiatzi F, Brandt DT, Schneikert J, Fuchs J, Grikscheit K, Wanzel M, Pavlakis E, Charles JP, Timofeev O, Nist A, Mernberger M, Kantelhardt EJ, Siebolts U, Bartel F, Jacob R, Rath A, Moll R, Grosse R, (2016). Mutant p53 promotes tumor progression and metastasis by the endoplasmic reticulum UDPase ENTPD5. 113, E8433-E8442.

  4. Wanzel M, Vischedyk JB, Gittler MP, Gremke N, Seiz JR, Hefter M, Noack M, Savai R, Mernberger M, Charles JP, Schneikert J, Bretz AC, Nist A, Stiewe T (2016). CRISPR-Cas9-based target validation for p53-reactivating model compounds. 12, 22–28.

  5. Charles JP, Fuchs J, Hefter M, Vischedyk JB, Kleint M, Vogiatzi F, Schäfer JA, Nist A, Timofeev O, Wanzel M, Stiewe T (2014). Monitoring the dynamics of clonal tumour evolution in vivo using secreted luciferases. Nat Commun 5, e3981.

  6. Timofeev O, Schlereth K, Wanzel M, Braun A, Nieswandt B, Pagenstecher A, Rosenwald A, Elsässer HPStiewe T (2013). p53 DNA binding cooperativity is essential for apoptosis and tumor suppression in vivo. 3, 585-97.

  7. Schlereth K, Beinoraviciute-Kellner R, Zeitlinger MK, Bretz AC, Sauer M, Charles JP, Vogiatzi F, Leich E, Samans B, Eilers M, Kisker C, Rosenwald A, Stiewe T (2010). DNA binding cooperativity of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell 38, 356-68.

  8. Stiewe T (2007). The p53 family in differentiation and tumorigenesis. 7, 165-8. (review article)

  9. Cam H, Griesmann H, Beitzinger M, Hofmann L, Beinoraviciute-Kellner R, Sauer M, Huttinger-Kirchhof N, Oswald C, Friedl P, Gattenlohner S, Burek C, Rosenwald A, Stiewe T (2006). p53 family members in myogenic differentiation and rhabdomyosarcoma development. 10, 281-93.

  10. Stiewe T, Pützer BM (2000). Role of the p53-homologue p73 in E2F1-induced apoptosis. 26, 464-9.

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