News

01.08.2019

Welcome interview: Eva Hörmanseder

Eva Hörmanseder is joining Helmholtz Zentrum München to establish her research group ‘Maintaining and Reprogramming Cell Fates’ at the Institute of Epigenetics and Stem Cells. Eva performed her PhD studies with Thomas Mayer at the University of Konstanz then moved to Cambridge to conduct her post-doctoral research with John Gurdon at the Gurdon Institute. Here she talks about her research and future goals as she establishes her team. 


 

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

I am curious to understand how the cells in our bodies remember their cell type, and how we can erase this cellular memory efficiently and safely to generate any new wanted cell type on demand. Differentiated cell types arise during embryonic development, and once they are committed to a certain fate, they normally do not change to another type. For example, a skin cell does not naturally change to, or give rise to a neuronal cell. However, this stable commitment of a cell can be reverted by certain experimental procedures, as for example when the nucleus of a specialised cell is transplanted to an enucleated egg. During this reprogramming, the gene expression pattern of the differentiated cell can be changed to that of an embryonic cell. I find this process so interesting, because identifying how reprogramming takes place can help us to understand how cells maintain their identity. This is important because many pathological conditions arise from loss of cell identity. In addition, the embryonic stem cells that can be obtained by reprogramming a specialised cell of one kind, e.g. a skin cell, can then be made to produce healthy specialized cells of another kind, e.g. brain cells. This has potential application in cell-replacement therapy, where these cells can compensate the loss of irreversibly damaged or defective cells.

 What are the main challenges in studying cell-fate reprogramming and how are you approaching them?

A main challenge in the field of cell-fate reprogramming is currently the low efficiency of the process, because most of the times, reprogramming is not successful and the establishment of new cell fates fails. The reason why adult body cells like skin do not respond to nuclear reprogramming is likely related to an inherent resistance of one kind of cell to change to another kind. Indeed, cells produced by transplanting the nucleus of a specialised cell to an egg often continue to show characteristics, such as expression of genes, of the specialised cell they were derived from. For example, reprogrammed skin cells continue to express skin genes and to fails to fully activate embryonic genes. In my lab, we will in particular look at the problem of inactivating genes during reprogramming, which is barely understood. We want to know how the active state of gene expression resists reprogramming and is instead maintained and propagated from one cell to the next. We also want to understand if the expression of genes from the old cell type prevents the generation of new cell types during reprogramming.  We will tackle these questions by combining the classic reprogramming approach of nuclear transplantation to frog eggs with state-of-the-art multiomics and machine learning approaches. In this way, we will understand how to improve cell fate reprogramming and hopefully, in the long run, aid the generation of high quality embryonic cells that can be used for cell replacement.

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

The vibrant and excellent scientific environment! To study cell-fate reprogramming, it is crucial to be surrounded by experts in stem cells, chromatin biology and epigenetics, like in the Institute of Epigenetics and Stem Cells. Additionally, I am also excited to work in an environment that will then allow me to directly translate my findings to other fields of research, as for example the generation of induced pluripotent stem cells, insulin producing beta cells, or regeneration.

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

It will be exciting to reveal the crucial mechanisms that resist the conversion of a differentiated cell identity to embryonic cell types during reprogramming in vertebrate eggs. Understanding the mechanisms that stabilise active states of gene expression would be especially interesting, as we do not understand and are currently lacking sufficient strategies to interfere with this aspect of cellular memory. Here, my research could lead to innovative technological approaches to specifically induce and modulate cell fate transitions. This would increase the efficiency, functionality and safety of reprogrammed cells. In addition, we will also gain novel insights into the epigenetic mechanisms that stabilise cell fates and that are impaired for example in cancer and in ageing. Such mechanisms could be targeted to prevent or treat diseases.  

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