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
• 2014-2019 Professor for Translational Cancer Research, University Medical Center Göttingen, Göttingen, Germany
• since 03/2019 Professor at Mayo Clinic College of Medicine, Rochester, Minnesota, USA



Major Research Interests

Overview
Tumor cells utilize a very diverse array of mechanisms to proliferate uncontrolled and metastasize. Irrespective of the underlying cause of a tumor, essentially all tumor-specific changes ultimately converge in the altered “expression” of genes in the cell. The goal of our work is to understand the molecular processes by which tumor-specific changes in gene activity lead to tumorigenesis and tumor progression. More importantly, we aim to utilize this information to identify better and more efficient therapies for various gastrointestinal tumors.

Targeting epigenetics for anti-cancer therapy
Since essentially all tumor-specific changes that occur during the formation and metastasis of cancer ultimately converge on the genetic material, it makes the processes which control gene activity ideal anti-cancer targets. In fact, researchers worldwide, as well as numerous pharmaceutical companies, have made significant progress in identifying new approaches to target “epigenetic” processes in cancer. Numerous clinical studies are ongoing which will help to determine which types of cancer may respond best to these therapies.

“Bromodomain” proteins in gastrointestinal cancers
The Johnsen group has been studying a specific group of “epigenetic” regulators called “bromodomain” proteins. These proteins essentially function as the “middle man” which convert different signaling processes into changes in the ability of a gene to be in an “on” or “off” state. Importantly, these proteins can be specifically targeted by small molecule drugs, many of which are in early clinical trials for different types of cancer. We are currently examining the molecular mechanisms by which bromodomain proteins work in cancer as well as deciphering the characteristics of individual tumors, which determine whether they will respond to these treatments. In this way, we hope to uncover new approaches to be able to identify specific therapeutic approaches for treating individual patients based on the molecular makeup of their tumors, an approach frequently referred to as “precision oncology”.


Selected Recent Publications



• Mishra VK, Subramaniam M, Kari V, Pitel KS, Baumgart SJ, Naylor RM, Nagarajan S, Wegwitz F, Ellenrieder V, Hawse JR, Johnsen SA (2017) Krüppel-like Transcription Factor KLF10 Suppresses TGFβ-Induced Epithelial-to-Mesenchymal Transition via a Negative Feedback Mechanism. Cancer Res. ;77(9):2387-2400.
• Nagarajan S, Bedi U, Budida A, Hamdan FH, Mishra VK, Najafova Z, Xie W, Alawi M, Indenbirken D, Knapp S, Chiang CM, Grundhoff A, Kari V, Scheel CH, Wegwitz F, Johnsen SA (2017) BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells. Nucleic Acids Res.;45(6):3130-3145.
• 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 (2017) Histone deacetylase class-I inhibition promotes epithelial gene expression in pancreatic cancer cells in a BRD4- and MYC-dependent manner. Nucleic Acids Res. doi: 10.1093/nar/gkx212.
• Xie W, Nagarajan S, Baumgart SJ, Kosinsky RL, Najafova Z, Kari V, Hennion M, Indenbirken D, Bonn S, Grundhoff A, Wegwitz F, Mansouri A, Johnsen SA(2017) RNF40 regulates gene expression in an epigenetic context-dependent manner. Genome Biol.;18(1):32.
• 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 (2017) BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire. Nucleic Acids Res.;45(1):127-141.
• 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 (2014) Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription. Cell Rep.;8(2):460-9.
• 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(2012) The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells. Mol Cell.;46(5):705-13.