The general aims of the division of Experimental Hematology are to obtain detailed knowledge on (molecular) mechanisms that determine hematopoietic stem cell self-renewal and differentiation, with the ultimate goal to deepen our insights in the development of acute myeloid leukemia (AML). We perform gene-function analyses in both primary human hematopoietic stem and progenitor cells utilizing various strategies including optimized lentiviral transduction protocols and inducible RNAi/CRISPR-Cas9 approaches. In addition, both using semi-high throughput in vitro cell culture screening systems and in vivo xenograft models we investigate the applicability of novel compounds to eradicate leukemic stem cells.
A 2-year technician position, funded by the Dutch Cancer Society (KWF), is available in the group of dr. V. van den Boom and prof.dr. J.J. Schuringa. Polycomb proteins are important epigenetic regulators that instruct cell fate decisions of normal hematopoietic stem cells and leukemic stem cells. We have previously shown that a specific non-canonical Polycomb complex, named PRC1.1, is essential for leukemic cell viability (Van den Boom et al. Cell Reports, 2016). Recently, we identified the deubiquitinase USP7 as an integral component of this complex. Within the current project we will perform an in-depth analysis of USP7 inhibitor sensitivity across a large cohort of AML patients, both in vitro and in vivo using xenograft mouse models. We will also dissect molecular pathways downstream of USP7 and investigate how USP7 inhibition induced PRC1.1 loss-of function affects leukemic stem cell viability.