Research

The research interest in my lab is to unravel the molecular pathways that regulate self-renewal and lineage commitment of stem cells. To facilitate our research we develop and apply genetic engineering tools.

Embryonic stem cells can proliferate without losing the capacity to differentiate into all three germ layers. Embryonic stem cells can grow in vitro using defined protocols. But it is difficult to expand other stem cell types or intermediate progenitor cells ex vivo. Therefore we developed conditional immortalization as a system for expansion of rare cell types. The system is based on tetracycline-regulated expression of SV40 Large T Antigen and enables the isolation of adult cell types for conditional expansion. We performed cellular cloning of mesenchymal stromal cells isolated from tet-regulated Large T Antigen mice and identified populations with distinct differentiation properties. 

Furthermore, we try to understand the epigenetic mechanisms that regulate stem cell differentiation in vitro and during mouse embryonic development. Lately, we concentrated on the role of the histone 3 lysine 27 demethylases UTX (KDM6A) and UTY (KDM6C). Using conditional mutagenesis in mice we showed that UTX, located on the X-chromosome, is required for embryonic development and haematopoiesis in adult female mice. Now we are studying the role of UTY during development and in adult haematopoiesis.

Finally, we develop and improve genetic engineering tools. We expanded the site-specific recombination toolbox by generating codon-optimized versions of Flp-, Dre- and Vika recombinases deleter and reporter mice. We established methods for Transposon mediated BAC transgenesis in embryonic stem cells and mouse zygotes. Further, we applied and developed CRISPR associated protocols for bi-allelic gene targeting in human embryonic stem cells. Currently we are developing a method for conditional depletion of proteins based on the Auxin inducible Degron system.