Interview Prof. Dr. med. Matthias Dobbelstein

What is your research focus?
The tumor suppressor p53 is subject to mutations in about 50% of all human cancers. Its activities are regulated by an ubiquitin ligase, MDM2. P53 is the world champion of all genes when it comes to the frequency of cancer-associated mutations. Thus, p53 and its binding partner MDM2 are at the center of cancer development. We are investigating what the MDM2 oncoprotein is doing in addition to antagonizing p53. According to our results, MDM2 is not only a regulator but also an effector of p53. Currently, we are trying to understand how MDM2 acts on chromatin, DNA replication, and gene expression. To this end, we use a variety of techniques and methods. We are performing DNA replication assays (“fiber assays”), chromatin immunoprecipitation, RNA sequencing analyses and immunofluorescence analyses.

We chose this research focus because of both the medical need to find better cures for cancer, and the curiosity to define the role of these genes that are subject to such frequent cancer-associated mutations. 

How did you become a researcher? What were the major influences in your career?
I became a researcher because I wanted to contribute to solving an unmet medical problem, and I loved thinking about how a cell decides when to divide. I also had an excellent mentor during my MD thesis. So right after finishing medical school, I decided to go for a postdoctoral internship. I then worked as a postdoc at Princeton University. Such an outstanding environment and a small campus with lots of interactions. Subsequently, my first group leader position was at Marburg University, at its Institute of Virology.

What can you tell us about your working group?
We have had a research lab at the UMG for 17 years now. The working group consists of 14 people in total, not including two additional research groups at the institute. Most of those 14 are doctoral students. I consider this a strength here at Göttingen: The MSc/PhD programs allow us to recruit excellent early-career scientists. We are also blessed by outstandingly dedicated technicians and experienced postdocs.

How can patients benefit from your research?
Patients will benefit mostly indirectly; we are doing basic research and we cannot predict whether or when patients will benefit from any specific research – although we strongly hope they will. Our basic research findings have contributed to the onset of clinical trials in the past. The cooperation of platinum-derived chemotherapeutics with chaperone inhibitors is an example.

What do you consider the biggest challenge in cancer research?
There are two major challenges. Firstly, finding targets that allow the specific elimination of cancer cells, without hurting normal cells and without giving rise to cancer cell resistance and, secondly, finding diagnostic approaches to detect cancer as early and as specifically as possible.

April 2022