Steven Johnsen. Full Professor for Translational Cancer Research 
University Medical Center Göttingen. Website
Medical Faculty. Department of General, Visceral & Pediatric Surgery. Justus-von-Liebig-Weg 11, 37077 Göttingen
Reseach subject
Identification and interrogation of epigenetic regulatory mechanisms controlling tumour initiation, progression and therapeutic responsiveness with a view towards translational potential to the clinical treatment of pancreatic, colorectal and esophageal cancers.
Summary
Cell fate determination during normal physiological processes requires the integration of multiple extrinsic and intrinsic signalling pathways, which ultimately converge on the genome to induce stable changes in gene expression. These gene expression changes require an intricate interplay between sequence-specific transcription factors and epigenetic regulatory proteins. Importantly, many major tumour genome sequencing projects have uncovered frequent alterations in epigenetic regulatory proteins, suggesting that genetic changes occurring during tumorigenesis or tumour progression help promote the effects elicited by the activation of oncogenic signalling to reverse cell differentiation programs and lead to pathogenesis.
Our group is examining the role of specific epigenetic regulators both in both normal physiological differentiation (e.g., in human osteoblasts) and in cancer (especially colorectal and pancreatic cancer, but also lung, prostate and breast cancer). In order to achieve this we utilize a variety of cell culture and molecular techniques to perform genome- and transcriptome-wide analyses of gene regulatory function and complement these with in vivo analysis of conditional gene knockouts and patient samples. Our goal is to gain a thorough understanding of the molecular epigenetic defects in specific subtypes of cancer which will allow us to uncover targeted therapy approaches which can be used in a “precision medicine” approach to treat cancer.
Publications
- 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. The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells. Mol Cell. 2012 Jun 8;46(5):705-13. doi: 10.1016/j.molcel.2012.05.022. PubMed PMID: 22681891.
- 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. Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription. Cell Rep. 2014 Jul 24;8(2):460-9. doi: 10.1016/j.celrep.2014.06.016. Epub 2014 Jul 10. PubMed PMID: 25017071; PubMed Central PMCID: PMC4747248.
- Najafova Z, Tirado-Magallanes R, Subramaniam M, Hossan T, Schmidt G, Nagarajan S, Baumgart SJ, Mishra VK, Bedi U, Hesse E, Knapp S, Hawse JR, Johnsen SA. BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire. Nucleic Acids Res. 2017 Jan 9;45(1):127-141. doi: 10.1093/nar/gkw826. Epub 2016 Sep 19. PubMed PMID: 27651452; PubMed Central PMCID: PMC5224504.
- Mishra VK, Wegwitz F, Kosinsky RL, Sen M, Baumgartner R, Wulff T, Siveke JT, Schildhaus HU, Najafova Z, Kari V, Kohlhof H, Hessmann E, Johnsen SA. Histone deacetylase class-I inhibition promotes epithelial gene expression in pancreatic cancer cells in a BRD4- and MYC-dependent manner. Nucleic Acids Res. 2017 Mar 27. doi: 10.1093/nar/gkx212. [Epub ahead of print] PubMed PMID: 28369619.
- Hessmann E, Johnsen SA, Siveke JT, Ellenrieder V. Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon? Gut. 2017 Jan;66(1):168-179. doi: 10.1136/gutjnl-2016-312539. Epub 2016 Nov 3. Review. PubMed PMID: 27811314; PubMed Central PMCID: PMC5256386.