In our research group, we investigate the regulation of haematopoietic stem cell (HSC) maintenance and fate by transcription factors and their target genes, determine whether these elements are altered in human leukaemias (in particular acute myeloid leukaemia, AML), and elucidate their contribution to leukaemogenesis. In addition, we investigate how cell extrinsic factors regulate HSC self-renewal and how they impact myeloid commitment. Our three main research lines are:
To determine the function of C/EBPa target genes in normal and malignant haematopoiesis.
To define the role of the b-catenin-TCF/LEF transcription-mediating complex in normal and aberrant haematopoiesis.
To assess the effects of inflammation/infection in HSC fitness and leukaemogenesis.
To reach these goals, we employ murine and human primary cells, as well as murine models. We perform a variety of in vitro assays to assess cell proliferation, apoptosis, colony-forming potential, re-plating ability, differentiation, and migration. Further, we carry out murine bone marrow cell transplantation assays, challenge mice with infectious agents, and perform HSC mobilization assays in vivo. Using primary cells from patients suffering from AML, we generate PDX models. To get novel insights into the molecular mechanism of stem cell regulation and transformation, we employ molecular biology approaches including RNA-seq, ATAC-seq and ChIP-seq/qPCR.
Together, we aim at understanding the mechanisms that control HSC maintenance and fate, and determine cell intrinsic and extrinsic factors that contribute to the development of leukaemia. Ultimately, our work will contribute to establishing knowledge for the development of better AML therapies.