Acute myeloid leukemia (AML) is a fatal disorder of the blood-forming bone marrow cells. In most patients, the cellular origin of AML is thought to be a normal hematopoietic stem cell (HSC) that through a series of genetic lesions gives rise to cells with leukemia-initiating capacity, also termed leukemia stem cells (LSCs), which propagate into frank AML. The major goals of our research is to identify therapeutic targets essential for LSCs, to generate novel insights into LSC biology, and to provide in vivo proof of concept for a therapeutic effect. To this end, we use pooled CRISPR/Cas9-screens and lentiviral barcoding of LSC. We have a translational focus and our research has already resulted in a spin-off company (Cantargia). If successful, our research may translate into new therapeutic opportunities in AML, a disease associated with poor prognosis.