The newly appreciated role of NPM1c on chromatin now gives us the opportunity to look at the mechanism of action of this oncoprotein from a different angle. For this we are employing several different strategies, such as chromatín-focused interactomics studies and proximity labelling mass-spec approaches to explore the chromatin complexes associated with NPM1c.

Components of the nuclear export pathway such as Exportin-1 (XPO1) and Nucleoporins such as NUP98 and NUP214 are commonly mutated in leukemia. Our data suggests that XPO1 is crucial for the chromatin recruitment of NPM1c. In our lab we want to understand how different components of the nuclear export machinery are hijacked in leukemia cells.

To understand the changes that occur when a normal stem or progenitor cell develops into a leukemia cell we are using NPM1c knock-in mouse models and patient derived xenograft models.

Many of the chromatin regulators we study have other important functions in the cell. We therefore use rapid degradation of our endogenous target proteins to study the direct consequences on chromatin and gene expression.

Description goes hereIn order to identify the mechanism of action our candidates epigenetic regulators, we perform CRISPR-based saturation mutagenesis screens. This allows us to identify essential domain specifically in our leukemia cell lines.

To identify novel epigenetic vulnerabilities in leukemia cells, we are using reporter cell lines to perform CRISPR and epigenetic drug screens. This will not only help us to understand more about the mechanism of epigenetic regulation oncogenic gene expression, but also to identify novel therapeutic strategies.