The research of Steven A. Johnsen, Ph.D., is focused on understanding the molecular underpinnings of gastrointestinal malignancies and noncancerous gastrointestinal diseases that place individuals at risk of developing cancer later in life. In particular, Dr. Johnsen's research group focuses on understanding the molecular underpinnings of pancreatic cancer and inflammatory bowel disease (IBD).
Pancreatic cancer is one of the most aggressive forms of cancer, and there is a dramatic need for improved therapeutic options for patients. Dr. Johnsen's group uses a wide variety of state-of-the-art molecular biology techniques and works closely with clinicians to identify molecular alterations that determine the course of pancreatic cancer progression and response to therapy. In particular, the group is seeking to identify the Achilles' heel in cancer-specific transcriptional mechanisms, which can be exploited for more effective tumor therapy.
Dr. Johnsen's research has been funded by numerous German and European agencies and is currently funded by the Mayo Clinic Pancreatic Cancer SPORE and startup funds from Mayo Clinic.
Transcriptional deregulation in pancreatic cancer. Dr. Johnsen's research group has extensive experience using a number of modern molecular techniques, in particular high-throughput sequencing techniques such as ChIP-, ATAC-, RNA- and ChRO-seq, to identify molecular determinants of cell fate specification. In particular, the group is examining transcription factor-driven epigenetic mechanisms and investigating under which context specific histone-modifying enzymes and epigenetic reader proteins (such as the BET family of bromodomain-containing proteins) may provide highly effective anti-cancer targets.
Using these approaches, Dr. Johnsen's group has successfully uncovered an essential role for ΔNp63, the N-terminal truncated isoform of p63, as a defining feature of the most aggressive form of pancreatic cancer, and uncovered additional transcription factor codependencies, which also may serve as therapeutic targets. Future work will continue to investigate these and other transcriptional and epigenetic pathways and uncover the utility of targeting them in anti-cancer treatment.
- IBD. A defining feature of many cancers is the highly suppressive environment that enables tumor cells to evade the immune system. In contrast, while pancreatic cancer represents an extreme example of inadequate immune responsiveness, IBD such as Crohn's disease or ulcerative colitis is a medical indication at the opposite end of the spectrum, where a hyperactive immune response and highly inflammatory environment underlie the disease physiology. Thus, Dr. Johnsen seeks to gain insights into the molecular mechanisms controlling both extremes in order to identify potential therapeutic targets that can be toggled in one direction or the other to help improve quality of life for individuals with IBD and, ultimately, eradicate the disease.
Significance to patient care
Dr. Johnsen's research serves not only to increase understanding of the molecular epigenetic and transcriptional mechanisms controlling pancreatic cancer development, progression and therapeutic responsiveness but also to unravel new targets for improving patient outcomes. Close collaborations with clinician-scientists provide important opportunities for translation of findings into clinical use for the treatment of pancreatic cancer and inflammatory bowel disease.
- Professor of Translational Cancer Research, Department of General, Visceral & Pediatric Surgery, University of Gottingen, Germany, 2014-2019
- Associate Professor of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany, 2012-2014
- Assistant Professor of Molecular Oncology, University of Gottingen, Germany 2007-2012
- Recipient, Ruth L. Kirschstein Predoctoral Individual National Research Service Award, National Institutes of Health, 2004-2007
- Humboldt Research Fellowship, Federal Ministry of Education and Research, Germany, 2003-2004