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Martin Zenke

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Martin Zenke
Born (1953-08-07) August 7, 1953 (age 71)
Korbach, Germany
NationalityGerman
Alma mater
Scientific career
Fieldsstem cell research, cell biology, molecular biology, cancer biology, bioengineering
Institutions
Thesis Transcription of SV40 Chromatin  (1982)

Martin Zenke (born August 7, 1953, in Korbach) is a German biochemist, cell biologist, professor for cell biology and scientist, who is conducting research on stem cells and biomedical engineering.

Biography

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Martin Zenke grew up in Korbach/Waldeck, Germany and finished school at Alte Landesschule in Korbach in 1972. He studied chemistry/biochemistry and medicine at Philipps-University, Marburg/Lahn, Germany (1972-1978) and graduated in 1978 with a study on “The ribonucleotide reductase in synchronized cultures of Saccharomyces cerevisiae (baker’s yeast)”.

Professional career

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In 1979 he moved to German Cancer Research Center (DKFZ), Heidelberg, Institute of Virology, Section DNA Tumor Viruses (Gerhard Sauer) for doctoral studies.[1] He received his PhD from Ruprecht-Karls-University, Heidelberg in 1982 on “Transcription of SV40 Chromatin”.[2]

From 1982 to 1985 Martin Zenke worked as postdoctoral fellow with Pierre Chambon at Université Louis Pasteur, Faculté de Médecine and Laboratoire de Genetique Moleculaire des Eucaryotes (LGME) in Strasbourg, France.[3][4][5] From 1985 to 1988 he was EMBL fellow and staff scientist[6] in the Differentiation Programme of European Molecular Biology Laboratory (EMBL), Heidelberg, Germany with Thomas Graf and Hartmut Beug.[7]

In 1988 he moved to the Research Institute of Molecular Pathology (IMP), Vienna, Austria to work as a Junior Scientist until 1995.[8][9][10][11][12][13] In 1992 he received his senior lecture qualification in Molecular Genetics from the Faculty of Natural Sciences, University of Vienna, Vienna, Austria. From 1995 to 2003 Martin Zenke was a Research Group Leader at Max Delbrück Center for Molecular Medicine (MDC) in Berlin, Germany.[14][15]

Since 2003 he is Professor of Cell Biology and Chairman, and the founding director of the Institute for Biomedical Engineering, Chair of Cell Biology at Rheinisch-Westfälische Technische Hochschule (RWTH) Medical School, Aachen, Germany.[16][17] Since 2008 he is a member of the "Central Ethics Committee for Stem Cell Research", Federal Ministry of Education and Research (BMBF) and Federal Ministry of Health (BMG), Berlin, Germany. 2011-2014 he was the Managing Director of Helmholtz-Institute for Biomedical Engineering (3 years legislative period), RWTH Aachen University, Aachen, Germany.

Main research

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1979-1986: SV40 Enhancer and SV40 Chromatin

In the 1980s Martin Zenke’s research focused on gene transcription and chromatin.[1] In 1986 he and his colleagues showed that transcriptional enhancers exhibit a modular structure and are composed of individual elements, which on their own are relatively weak but act in synergy, and thereby build up enhancer activity.[3][4][5] This is textbook knowledge nowadays but in the 1980s enhancers were initially thought to boost transcription by a unique and particular strong enhancer sequence and factor. Martin Zenke’s seminal work is depicted and referenced in Lewin’s Genes IX,[18] the standard molecular biology textbook.

1986-1998: The erbA Oncogene and Red Blood Cell Differentiation

In 1988 Martin Zenke started to work on retroviral oncogenes, in particular on the v-erbA and v-rel oncogenes.[7][9][10][13] He found that the v-erbA oncogene is a loss of function version of the c-erbA/thyroid hormone receptor and acts as a dominant negative transcriptional repressor.[7][9][10] This was the first description of oncogenic activity by loss-of-function mutation. [19][20] This discovery was surprising, since up to then oncogenic potential was believed to be solely due to activating mutations.

The erbA work led Martin Zenke to work on red blood cell differentiation,[11][12][14] focussing on the just discovered GATA transcription factors.[11][12] He found that GATA-1 promotes red blood cell development[12] whereas GATA-2 blocks red blood cell development.[11] These findings were the first to suggest GATA-2 function in early blood cell development.

1995-today: Stem Cells and Antigen Presenting Dendritic Cells

At the beginning of the 1990s, the studies on the v-rel oncogene[13] led Martin Zenke to work on antigen presenting dendritic cells (DC), a specific immune cell, which is important for immunity and immune tolerance. DC biology was poorly understood at that time and Martin Zenke was one of the first to apply gene expression profiling with DNA microarrays for gene mining. This work led to the discovery of the Id2 transcription factor in DC development.[15] The Id2 gene data sets received accession numbers 1 and 2 (E-MEXP-1 and E-MEXP-2) of the ArrayExpress database,[21] one of the two major genomic data repositories, which now contains several million entries.

The DC work is being followed mainly in the mouse system,[22][23] to study gene circuitries of DC development and function using RNA-Seq, ChIP-seq, ATAC-seq, chromosome conformation capture (4C) and CRISPR/Cas9 gene editing,[24] and more recently in the human system using induced pluripotent stem cells (iPS cells).

2005-today: Pluripotent Stem Cells and Disease Modeling

Hematopoietic stem cells have been Martin Zenke’s prime interest for many years and in the 2005s he broadened his interest to also include pluripotent stem cells, such as embryonic stem cells (ES cells) and the more recently discovered induced pluripotent stem cells (iPS cells). [25][26][27]

A particular focus is on disease and patient specific iPS cells for disease modeling and compound screening. Emphasis is put on studying hematopoietic malignancies,[27][28] thereby building on the close collaboration with preclinical and clinical partners. This focus also includes developing animal models of diseases and laboratory automation for cell production.

Martin Zenke also worked also on technology development: Automatic DNA sequencing,[29] and gene delivery into cells.[30][31]

Publications

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References

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  1. ^ a b Zenke, M; Sauer, G (Aug 11, 1982). "Spliced and unspliced virus specific RNA sequences are associated with purified simian virus 40 chromatin". Nucleic Acids Research. 10 (15): 4543–50. doi:10.1093/nar/10.15.4543. PMC 321110. PMID 6290985.
  2. ^ Zenke, Martin (1982). Transkription von SV40 Chromatin (Thesis) (in German). Frankfurt, Signatur: H 90b/9811: Heidelberg, Univ., Diss., 1982. p. 118.{{cite thesis}}: CS1 maint: location (link)
  3. ^ a b Zenke, M; Grundström, T; Matthes, H; Wintzerith, M; Schatz, C; Wildeman, A; Chambon, P (February 1986). "Multiple sequence motifs are involved in SV40 enhancer function". The EMBO Journal. 5 (2): 387–97. doi:10.1002/j.1460-2075.1986.tb04224.x. PMC 1166744. PMID 3011406.
  4. ^ a b Wildeman, A G; Zenke, M; Schatz, C; Wintzerith, M; Grundström, T; Matthes, H; Takahashi, K; Chambon, P (June 1986). "Specific protein binding to the simian virus 40 enhancer in vitro". Molecular and Cellular Biology. 6 (6): 2098–2105. doi:10.1128/mcb.6.6.2098. PMC 367750. PMID 3023918.
  5. ^ a b Davidson, I; Fromental, C; Augereau, P; Wildeman, A; Zenke, M; Chambon, P (Oct 9–15, 1986). "Cell-type specific protein binding to the enhancer of simian virus 40 in nuclear extracts". Nature. 323 (6088): 544–8. Bibcode:1986Natur.323..544D. doi:10.1038/323544a0. PMID 3020434. S2CID 4327015.
  6. ^ Zenke, Martin. "EMBL Alumni". Retrieved 26 April 2012.
  7. ^ a b c Zenke, M; Kahn, P; Disela, C; Vennström, B; Leutz, A; Keegan, K; Hayman, MJ; Choi, HR; Yew, N; Engel, JD (Jan 15, 1988). "v-erbA specifically suppresses transcription of the avian erythrocyte anion transporter (band 3) gene". Cell. 52 (1): 107–19. doi:10.1016/0092-8674(88)90535-1. PMID 2830979. S2CID 29464344.
  8. ^ Research Institute of Molecular Pathology, former groups
  9. ^ a b c Zenke, M; Muñoz, A; Sap, J; Vennström, B; Beug, H (Jun 15, 1990). "v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA". Cell. 6. 61 (6): 1035–49. doi:10.1016/0092-8674(90)90068-P. PMID 1972036. S2CID 36806100.
  10. ^ a b c Disela, C; Glineur, C; Bugge, T; Sap, J; Stengl, G; Dodgson, J; Stunnenberg, H; Beug, H; Zenke, M (November 1991). "v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII". Genes & Development. 5 (11): 2033–2047. doi:10.1101/gad.5.11.2033. PMID 1682217.
  11. ^ a b c d Briegel, K; Lim, K C; Plank, C; Beug, H; Engel, J D; Zenke, M (June 1993). "Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner". Genes & Development. 7 (6): 1097–1109. doi:10.1101/gad.7.6.1097. PMID 8504932.
  12. ^ a b c d Briegel, K.; Bartunek, P.; Stengl, G.; Lim, K.C.; Beug, H.; Engel, J.D.; Zenke, M. (1 December 1996). "Regulation and function of transcription factor GATA-1 during red blood cell differentiation". Development. 122 (12): 3839–3850. doi:10.1242/dev.122.12.3839. PMID 9012505.
  13. ^ a b c Boehmelt, G; Madruga, J; Dörfler, P; Briegel, K; Schwarz, H; Enrietto, PJ; Zenke, M (Jan 27, 1995). "Dendritic cell progenitor is transformed by a conditional v-Rel estrogen receptor fusion protein v-RelER". Cell. 80 (2): 341–52. doi:10.1016/0092-8674(95)90417-4. PMID 7834754.
  14. ^ a b Panzenböck, Birgit; Bartunek, Petr; Mapara, Markus Y.; Zenke, Martin (15 November 1998). "Growth and Differentiation of Human Stem Cell Factor/Erythropoietin-Dependent Erythroid Progenitor Cells In Vitro". Blood. 92 (10): 3658–3668. doi:10.1182/blood.V92.10.3658. PMID 9808559.
  15. ^ a b Hacker, C; Kirsch, RD; Ju, XS; Hieronymus, T; Gust, TC; Kuhl, C; Jorgas, T; Kurz, SM; Rose-John, S; Yokota, Y; Zenke, M (April 2003). "Transcriptional profiling identifies Id2 function in dendritic cell development". Nature Immunology. 4 (4): 380–6. doi:10.1038/ni903. PMID 12598895. S2CID 35329390.
  16. ^ Zenke, Martin. "Dr. Martin Zenke nimmt Ruf auf C4-Professur in Aachen an". public relations department of the Max Delbrück Center for Molecular Medicine. Retrieved 26 April 2012.[permanent dead link‍]
  17. ^ Zenke, Martin. "currently appointed professors RWTH 2003". RWTH Aachen. Retrieved 26 April 2012.
  18. ^ Lewin, B. (2008). Genes IX. Jones and Bartlett Publishers. ISBN 978-0763752224.
  19. ^ Weinberg, Robert A. (22 November 1991). "Tumor Suppressor Genes". Science. 254 (5035): 1138–1146. Bibcode:1991Sci...254.1138W. doi:10.1126/science.1659741. PMID 1659741.
  20. ^ Lewin, Benjamin (January 1991). "Oncogenic conversion by regulatory changes in transcription factors". Cell. 64 (2): 303–312. doi:10.1016/0092-8674(91)90640-k. PMID 1988149. S2CID 26966778.
  21. ^ "ArrayExpress < EMBL-EBI". www.ebi.ac.uk.
  22. ^ Seré, Kristin; Baek, Jea-Hyun; Ober-Blöbaum, Julia; Müller-Newen, Gerhard; Tacke, Frank; Yokota, Yoshifumi; Zenke, Martin; Hieronymus, Thomas (November 2012). "Two Distinct Types of Langerhans Cells Populate the Skin during Steady State and Inflammation". Immunity. 37 (5): 905–916. doi:10.1016/j.immuni.2012.07.019. PMID 23159228.
  23. ^ Romani, Nikolaus; Tripp, Christoph; Stoitzner, Patrizia (November 2012). "Langerhans Cells Come in Waves". Immunity. 37 (5): 766–768. doi:10.1016/j.immuni.2012.10.013. PMC 4285563. PMID 23159223.
  24. ^ Lin, Qiong; Chauvistré, Heike; Costa, Ivan G.; Gusmao, Eduardo G.; Mitzka, Saskia; Hänzelmann, Sonja; Baying, Bianka; Klisch, Theresa; Moriggl, Richard; Hennuy, Benoit; Smeets, Hubert; Hoffmann, Kurt; Benes, Vladimir; Seré, Kristin; Zenke, Martin (17 October 2015). "Epigenetic program and transcription factor circuitry of dendritic cell development". Nucleic Acids Research. 43 (20): 9680–9693. doi:10.1093/nar/gkv1056. PMC 4787753. PMID 26476451.
  25. ^ Ruau, David; Ensenat-Waser, Roberto; Dinger, Timo C.; Vallabhapurapu, Duttu S.; Rolletschek, Alexandra; Hacker, Christine; Hieronymus, Thomas; Wobus, Anna M.; Müller, Albrecht M.; Zenke, Martin (April 2008). "Pluripotency Associated Genes Are Reactivated by Chromatin-Modifying Agents in Neurosphere Cells". Stem Cells. 26 (4): 920–926. doi:10.1634/stemcells.2007-0649. PMID 18203677. S2CID 41497590.
  26. ^ Kim, Jeong Beom; Zaehres, Holm; Wu, Guangming; Gentile, Luca; Ko, Kinarm; Sebastiano, Vittorio; Araúzo-Bravo, Marcos J.; Ruau, David; Han, Dong Wook; Zenke, Martin; Schöler, Hans R. (July 2008). "Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors". Nature. 454 (7204): 646–650. Bibcode:2008Natur.454..646K. doi:10.1038/nature07061. PMID 18863515. S2CID 4318637.
  27. ^ a b Toledo, Marcelo A. S.; Gatz, Malrun; Sontag, Stephanie; Gleixner, Karoline V.; Eisenwort, Gregor; Feldberg, Kristina; Hamouda, Ahmed E. I.; Kluge, Frederick; Guareschi, Riccardo; Rossetti, Giulia; Sechi, Antonio S.; Dufva, Olli M. J.; Mustjoki, Satu M.; Maurer, Angela; Schüler, Herdit M.; Goetzke, Roman; Braunschweig, Till; Kaiser, Anne; Panse, Jens; Jawhar, Mohamad; Reiter, Andreas; Hilberg, Frank; Ettmayer, Peter; Wagner, Wolfgang; Koschmieder, Steffen; Brümmendorf, Tim H.; Valent, Peter; Chatain, Nicolas; Zenke, Martin (15 April 2021). "Nintedanib targets KIT D816V neoplastic cells derived from induced pluripotent stem cells of systemic mastocytosis". Blood. 137 (15): 2070–2084. doi:10.1182/blood.2019004509. PMID 33512435. S2CID 231758973.
  28. ^ Dorrance, Adrienne (15 April 2021). ""Mast"ering drug discovery with iPSCs". Blood. 137 (15): 1993–1994. doi:10.1182/blood.2020010456. PMID 33856443. S2CID 233243904.
  29. ^ Ansorge, Wilhelm; Sproat, Brian; Stegemann, Josef; Schwager, Christian; Zenke, Martin (1987). "Automated DNA sequencing: ultrasensitive detection of fluorescent bands during electrophoresis". Nucleic Acids Research. 15 (11): 4593–4602. doi:10.1093/nar/15.11.4593. PMC 340882. PMID 3588303.
  30. ^ Zenke, M.; Steinlein, P.; Wagner, E.; Cotten, M.; Beug, H.; Birnstiel, M. L. (1 May 1990). "Receptor-mediated endocytosis of transferrin-polycation conjugates: an efficient way to introduce DNA into hematopoietic cells". Proceedings of the National Academy of Sciences. 87 (10): 3655–3659. Bibcode:1990PNAS...87.3655Z. doi:10.1073/pnas.87.10.3655. PMC 53961. PMID 2339110.
  31. ^ Diebold, Sandra S.; Kursa, Margaretha; Wagner, Ernst; Cotten, Matt; Zenke, Martin (July 1999). "Mannose Polyethylenimine Conjugates for Targeted DNA Delivery into Dendritic Cells". Journal of Biological Chemistry. 274 (27): 19087–19094. doi:10.1074/jbc.274.27.19087. PMID 10383411.
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