Johnsen, Steven, Prof. Dr. - Translational Cancer Research
1999-2002 Ph.D. Mayo Clinic College of Medicine, Rochester, Minnesota, USA
2003-2006 Doctoral Fellow, Center for Molecular Neurobiology (ZMNH), Hamburg, Germany
2006-2007 Post-Doctoral Fellow, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
2007-2012 Assistant Professor in Molecular Oncology, University of Göttingen Medical Faculty, Göttingen, Germany
2012-2014 Assoc. Professor in Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Since 2014 Professor for Translational Cancer Research, University Medical Center Göttingen, Göttingen, Germany
Major Research Interests
The 3 x 109 bp of DNA in the human genome is organized in several higher order chromatin structures which allow for the correct packaging and “reading” of the genetic material. Importantly, the proper regulation of gene transcription, DNA replication and probably most DNA-associated nuclear functions is regulated by the post-translational modification of histone proteins. Our group is focused on the role and regulation of chromatin modifications in controlling transcription and transcription-coupled nuclear processes during tumorigenesis. The primary interest of our work is the monoubiquitination of histone H2B (H2Bub1) which appears to serve a tumor suppressor role in breast cancer and is tightly associated to active gene transcription. Although this modification has been studied extensively in yeast, relatively little is known about its function and regulation in higher eukaryotic organisms.
In our future work we will address:
1. The role of H2B modifying enzymes in tumorigenesis in transgenic mouse models.
2. The regulation of tumorigenic properties and metastasis by epigenetic modifiers.
3. How epigenetic modifications control cellular differentiation and dedifferentiation.
4. The function of dynamics changes in chromatin structure in various nuclear processes
Including transcription and DNA repair.
5. The importance and regulation of 3-dimensional nuclear organization in the control
of nuclear hormone receptor-regulated gene transcription.
Selected Recent Publications
Epigenetic plasticity: A central regulator of epithelial-to-mesenchymal transition in cancer. Bedi U, Mishra VK, Wasilewski D, Scheel C, Johnsen SA. Oncotarget. 2014 Apr 30;5(8):2016-29.
SUPT6H controls estrogen receptor activity and cellular differentiation by multiple epigenomic mechanisms. Bedi U, Scheel AH, Hennion M, Begus-Nahrmann Y, Rüschoff J, Johnsen SA. Oncogene. 2014 Jan 20. doi: 10.1038/onc.2013.558.
The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells. Karpiuk O, Najafova Z, Kramer F, Hennion M, Galonska C, König A, Snaidero N, Vogel T, Shchebet A, Begus-Nahrmann Y, Kassem M, Simons M, Shcherbata H, Beissbarth T, Johnsen SA. Mol Cell. 2012 Jun 8;46(5):705-13. doi: 10.1016/j.molcel.2012.05.022.
Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependent monoubiquitination of histone H2B. Prenzel T, Begus-Nahrmann Y, Kramer F, Hennion M, Hsu C, Gorsler T, Hintermair C, Eick D, Kremmer E, Simons M, Beissbarth T, Johnsen SA. Cancer Res. 2011 Sep 1;71(17):5739-53. doi: 10.1158/0008-5472.CAN-11-1896.
CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing. Pirngruber J, Shchebet A, Schreiber L, Shema E, Minsky N, Chapman RD, Eick D, Aylon Y, Oren M, Johnsen SA. EMBO Rep. 2009 Aug;10(8):894-900. doi: 10.1038/embor.2009.108.
The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Shema E, Tirosh I, Aylon Y, Huang J, Ye C, Moskovits N, Raver-Shapira N, Minsky N, Pirngruber J, Tarcic G, Hublarova P, Moyal L, Gana-Weisz M, Shiloh Y, Yarden Y, Johnsen SA, Vojtesek B, Berger SL, Oren M. Genes Dev. 2008 Oct 1;22(19):2664-76. doi: 10.1101/gad.1703008..
Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription. Nagarajan S, Hossan T, Alawi M, Najafova Z, Indenbirken D, Bedi U, Taipaleenmäki H, Ben-Batalla I, Scheller M, Loges S, Knapp S, Hesse E, Chiang CM, Grundhoff A, Johnsen SA. Cell Reports, 2014 Jul 24;8(2):460-9. doi: 10.1016/j.celrep.2014.06.016. Epub 2014 Jul 10.
Prof. Dr. Steven Johnsen
University Medical Center Göttingen
Clinic for General, Visceral and Pediatric Surgery