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 primary human hematopoietic stem and progenitor cells utilizing various strategies including optimized lentiviral transduction protocols and inducible RNAi/CRISPR-Cas9 approaches. Furthermore, we use proteomics approaches for quantitative protein interactome analyses and ChIP-qPCR/seq approaches to investigate epigenetic regulation of gene expression in normal versus leukemic cells.
A four-year PhD/AIO 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. The aim of this study is to further dissect the exact molecular function of the PRC1.1 complex and USP7 in leukemic cells using state-of-the-art proteomics analyses, ChIP-seq/RNA-seq analysis in primary AML patient cells, and inducible knockout models. Furthermore, we will test the effectiveness of USP7 inhibitors in eradicating leukemic stem cells, both in vitro and in vivo using xenograft mouse models.