Walter Birchmeier

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Walter Birchmeier

Walter Birchmeier (born July 8, 1943 in Würenlingen , Canton Aargau , Switzerland) is a German-Swiss developmental biologist and cancer researcher at the Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association , Berlin. From 2004 to 2008 he was Scientific Director of the MDC.

biography

Walter Birchmeier worked as a primary school teacher from 1964 to 1966. He studied biology at the University of Zurich , where he received his doctorate with distinction. He worked as a postdoc with Gottfried Schatz at Cornell University Ithaca (USA) and at the Biozentrum of the University of Basel , and with Jon Singer at the University of California San Diego. He then carried out research as a junior group leader at the Friedrich Miescher Laboratory of the Max Planck Society in Tübingen, and as a full professor at the Institute for Cell Biology (tumor research) at the University Hospital Essen. In 1993 he moved to the Max Delbrück Center for Molecular Medicine (MDC) and was appointed professor at the Charité / Medical University of Berlin.

research

In early work, Walter Birchmeier and his research group characterized cytoskeletal proteins and the cell adhesion molecule E-cadherin, which is found in normal epithelial cells. They discovered that E-cadherin is present in reduced quantities in invasive and metastatic epithelial cells, and that this loss triggers epithelial-mesenchymal transitions (EMT). Transfection of E-cadherin into carcinoma cells converts them back into normal, non-invasive epithelial cells.

Walter Birchmeier's most important discoveries relate to two cellular signaling systems, Wnt / beta-catenin and Met / Gab1 / Shp2. Mutations or changes in the regulation of these signaling systems are responsible for developmental disorders and cancer. Walter Birchmeier and his laboratory discovered that beta-catenin binds to transcription factors of the Lef1 / Tcf family and that this mechanism transports beta-catenin into the cell nucleus and thus regulates target genes of the Wnt signal transmission system. The group also showed that beta-catenin is recruited into a protein degradation complex of Axin2 / Conductin, GSK3-beta and APC. The protein degradation complex is often changed in tumors, whereby beta-catenin is stabilized and constantly switches on Wnt target genes. The group also investigated scatter factor / hepazocyte growth factor (SF / HGF) and its receptor, the tyrosine kinase Met, in the morphogenesis of epithelial cells. They found that Met signals in the cytoplasm are transmitted by the multi-adapter protein Gab1 and the tyrosine phosphatase Shp2.

Birchmeier's laboratory also used mouse mutagenesis to characterize the normal function of Wnt / beta-catenin and Gab1 / Shp2 signaling. They showed that mutations of beta-catenin cause defects in gastrulation and, through conditional mutagenesis, that beta-catenin controls the development of progenitor cells and stem cells of the nervous system, hair and heart. Gab1 and Shp2 signals are required by precursor cells in the hair follicle and in the kidney. The group investigated oncogenic mutations of beta-catenin and SF / HGF / Met in mouse cancer stem cells. They showed that beta-catenin interacts with the epigenetic factor Mll1 and that the expression of target genes of the beta-catenin and Met signaling pathways predict the outcome of human ear, nose and breast cancers. In collaboration with the Leibniz Institute for Molecular Pharmacology in Berlin, the group has developed small-molecule substances that inhibit Wnt / beta-catenin and Met / Shp2 signaling and can thus suppress tumor development.

Walter Birchmeier is married to the biologist Carmen Birchmeier-Kohler , who studies the developmental processes in the nervous system and muscles.

Honors and memberships

Web links

Website of Walter Birchmeier's working group

Individual evidence

  1. ↑ MDC press release from 2006
  2. ^ TE Kreis, W. Birchmeier: Stress fiber sarcomeres of fibroblasts are contractile . In: Cell . tape 22 , 2 Pt 2, November 1980, ISSN  0092-8674 , p. 555-561 , PMID 6893813 .
  3. ↑ BA Imhof, HP Vollmers, SL Goodman, W. Birchmeier: Cell-cell interaction and polarity of epithelial cells: specific perturbation using a monoclonal antibody . In: Cell . tape 35 , 3 Pt 2, December 1983, ISSN  0092-8674 , p. 667-675 , PMID 6652682 .
  4. ↑ J. Behrens, MM Mareel, FM Van Roy, W. Birch Meier: Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of Uvomorulin-mediated cell-cell adhesion . In: The Journal of Cell Biology . tape 108 , no. 6 , June 1989, ISSN  0021-9525 , pp. 2435-2447 , PMID 2661563 , PMC 2115620 (free full text).
  5. ↑ J. Behrens, JP von Kries, M. Kühl, L. Bruhn, D. Wedlich: Functional interaction of beta-catenin with the transcription factor LEF-1 . In: Nature . tape 382 , no. 6592 , August 15, 1996, ISSN  0028-0836 , p. 638-642 , doi : 10.1038 / 382638a0 , PMID 8757136 .
  6. ↑ J. Behrens, BA Jerchow, M. Würtele, J. Grimm, C. Asbrand: Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta . In: Science (New York, NY) . tape 280 , no. 5363 , April 24, 1998, ISSN  0036-8075 , p. 596-599 , PMID 9554852 .
  7. ↑ KM Weidner, J. Behrens, J. Vandekerckhove, W. Birchmeier: Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells . In: The Journal of Cell Biology . tape 111 , 5 Pt 1, November 1, 1990, ISSN  0021-9525 , p. 2097-2108 , PMID 2146276 , PMC 2116316 (free full text).
  8. ↑ KM Weidner, S. Di Cesare, M. Sachs, V. Brinkmann, J. Behrens: Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis . In: Nature . tape 384 , no. 6605 , November 14, 1996, ISSN  0028-0836 , p. 173-176 , doi : 10.1038 / 384173a0 , PMID 8906793 .
  9. ↑ U. Schaeper, NH Gehring, KP Fuchs, M. Sachs, B. Kempkes: Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses . In: The Journal of Cell Biology . tape 149 , no. 7 , June 26, 2000, ISSN  0021-9525 , p. 1419-1432 , PMID 10871282 , PMC 2175135 (free full text).
  10. ↑ J. Huelsken, R. Vogel, V. Brinkmann, B. Erdmann, C. Birch Meier: Requirement for beta-catenin in the anterior-posterior axis formation in mice . In: The Journal of Cell Biology . tape 148 , no. 3 , February 7, 2000, ISSN  0021-9525 , p. 567-578 , PMID 10662781 , PMC 2174807 (free full text).
  11. ↑ Tamara Grigoryan, Peter Wend, Alexandra Klaus, Walter Birchmeier: Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice . In: Genes & Development . tape 22 , no. 17 , September 1, 2008, ISSN  0890-9369 , p. 2308-2341 , doi : 10.1101 / gad.1686208 , PMID 18765787 , PMC 2749675 (free full text).
  12. ↑ J. Huelsken, R. Vogel, B. Erdmann, G. Cotsarelis, W. Birchmeier: beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin . In: Cell . tape 105 , no. 4 , May 18, 2001, ISSN  0092-8674 , p. 533-545 , PMID 11371349 .
  13. ↑ Özlem Akilli Öztürk, Hubert Pakula, Jolanta Chmielowiec, Jingjing Qi, Simone Stein: Gab1 and Mapk Signaling Are Essential in the Hair Cycle and Hair Follicle Stem Cell Quiescence . In: Cell Reports . tape 13 , no. 3 , October 20, 2015, ISSN  2211-1247 , p. 561-572 , doi : 10.1016 / j.celrep.2015.09.015 , PMID 26456821 .
  14. ^ Regina Willecke, Julian Heuberger, Katja Grossmann, Odyssé Michos, Kai Schmidt-Ott: The tyrosine phosphatase Shp2 acts downstream of GDNF / Ret in branching morphogenesis of the developing mouse kidney . In: Developmental Biology . tape 360 , no. 2 , December 15, 2011, ISSN  1095-564X , p. 310-317 , doi : 10.1016 / j.ydbio.2011.09.029 , PMID 22015719 .
  15. ↑ Peter Wend, Liang Fang, Qionghua Zhu, Jörg H. Schipper, Christoph Loddenkemper: Wnt / β-catenin signaling induces MLL to create epigenetic changes in salivary gland tumors . In: The EMBO journal . tape 32 , no. 14 , July 17, 2013, ISSN  1460-2075 , p. 1977–1989 , doi : 10.1038 / emboj.2013.127 , PMID 23736260 , PMC 3715856 (free full text).
  16. ↑ Jane D. Holland, Balázs Györffy, Regina Vogel, Klaus Eckert, Giovanni Valenti: Combined Wnt / β-catenin, Met, and CXCL12 / CXCR4 signals characterize basal breast cancer and predict disease outcome . In: Cell Reports . tape 5 , no. 5 , December 12, 2013, ISSN  2211-1247 , p. 1214-1227 , doi : 10.1016 / j.celrep.2013.11.001 , PMID 24290754 .
  17. ↑ Liang Fang, Qionghua Zhu, Martin Neuenschwander, Edgar Specker, Annika Wulf-Goldenberg: A Small-Molecule Antagonist of the β-Catenin / TCF4 Interaction Blocks the Self-Renewal of Cancer Stem Cells and Suppresses Tumorigenesis . In: Cancer Research . tape 76 , no. 4 , February 15, 2016, ISSN  1538-7445 , p. 891-901 , doi : 10.1158 / 0008-5472.CAN-15-1519 , PMID 26645562 .
  18. ↑ Linxiang Lan, Jane D. Holland, Jingjing Qi, Stefanie Grosskopf, Jörg Rademann: Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice . In: The EMBO journal . tape 34 , no. 11 , June 3, 2015, ISSN  1460-2075 , p. 1493-1508 , doi : 10.15252 / embj.201489004 , PMID 25736378 , PMC 4474526 (free full text).
personal data
SURNAME Birchmeier, Walter
BRIEF DESCRIPTION German-Swiss developmental biologist and cancer researcher
DATE OF BIRTH July 8, 1943
PLACE OF BIRTH Würenlingen