Welcome interview: Stephan Hamperl

Stephan Hamperl, Junior Group Leader at the IES. Source: IES/HMGU

Stephan Hamperl recently joined Helmholtz Zentrum München to establish his research group Chromatin Dynamics and Genome Stability at the Institute of Epigenetics and Stem Cells.  Stephan performed his PhD studies with Joachim Griesenbeck at the University of Regensburg and then moved to Stanford University in California to conduct his post-doctoral research with Karlene Cimprich.  Here he talks about his research and future goals as he establishes his team.

Let’s start with a general overview and hearing about the main aims of your research:

Chromosomes are fascinating structures – highly compacted to fit in our nucleus but at the same time highly dynamic to allow access to the cellular machineries involved in DNA repair, DNA replication, transcription, chromosome organization and many more. This versatility is essential for cell survival, proliferation, cell cycle progression and reproduction. I’m fascinated by the fact that all of these fundamental processes use the same DNA template, often in opposing directions and at different rates. How do cells regulate and coordinate all this traffic on our genome so that they don’t interfere with each other? One major aim of my research team is to understand how cells regulate gene expression with the DNA replication program and therefore prevent collisions between the transcription and replication machineries. We also aim to identify hotspots in our genome where such conflicts occur and identify the molecular players and chromatin-based mechanisms that are involved to resolve and overcome them.

What are the main challenges in studying transcription-replication interference and how are you approaching them?

The main challenge to study such conflicts is that they are rare events and occur transiently at random positions on the genome so that it is difficult to accurately detect and monitor them. To overcome this, we have established model systems where we can induce transcription-replication conflicts on specific model loci in a controlled manner. In the future, we plan to extend these analyses and detect conflicts on the endogenous genome with single-cell and single-molecule based assays.

What attracted you to starting your lab at the Institute Epigenetics and Stem Cells at Helmholtz Zentrum München?

When establishing my group, I was looking for a stimulating environment where I can bring in my own knowledge but also extend and complement my scientific questions to other model systems. The focus of the IES at Helmholtz Zentrum München on cellular plasticity and cell fate decisions was ideal as these decisions are associated with massive changes of the chromatin structure and it will be interesting to see how the coordination of gene expression and DNA replication is affected when the cell changes its identity. In addition, Munich offers a great research landscape to do chromatin research and there are many excellent groups within the Helmholtz but also at other institutes in Munich with great opportunities for collaborations.

What excites you the most about the future of your research?

I think the most exciting avenue of my research is that the coordination of these processes must be dynamic and adjusted to the current situation of the cell. There are many physiological (e.g. development or growth factor/hormone stimulation) as well as pathological examples (oncogene activation or viral infections), where certain transcriptional programs are turned on. It is feasible that this increased transcriptional output may come at the cost of more frequent interference with the replication machinery. Intriguingly, all of these conditions are associated with increased genomic instability and chromosomal rearrangements, both hallmarks of cancer genomes. A better understanding of these conflicts and how to avoid them may therefore also inform about novel genetic and epigenetic therapeutic targets of human diseases.

Visit Stephan’s webpage for more information on his research and ongoing activities at the IES.