Sten Eirik W. Jacobsen

Establishing the normal lineage commitment pathways from hematopoietic stem cells to lineage-restricted progenitors remains an important goal towards unravelling the regulation of blood lineage development, and how this is perturbed in hematological malignancies.

The Jacobsen Lab has for more than a decade had a focus on establishing key lineage commitment/restriction steps and blood lineage pathways in normal hematopoiesis (Adolfsson Cell 2005; Boiers Cell Stem Cell 2013; Sanjuan-Pla Nature 2013; Luis Nature Immunology 2016; Drissen Nature Immunology 2016). Distinct cancer stem cells (CSCs) might underlie relapses after complete remissions. The Jacobsen Lab has identified and characterized distinct and rare candidate CSCs and their therapeutic resistance in the chronic hematological malignancies myelodysplastic syndromes (MDS; Tehranchi New Engl J Med 2010; Woll Cancer Cell 2014) and myeloproliferative neoplasms (Mead N Engl J Med 2012; Giustacchini  Nature Medicine 2017). 

The current focus of the research program of the Jacobsen group is to apply different genetic tools and functional as well as molecular single cell analysis to unravel the dynamics of distinct stem and progenitor cells in unperturbed hematopoiesis as well as in response to distinct challenges, in mice as well as in normal human subjects. We also model the impact of recurrent genomic lesions at distinct stages of hematopoietic lineage commitment, to identify key cellular targets and molecular events in the transformation from normal to malignant hematopoiesis. In parallel we track the cellular fate and genomic evolution of clonal hematopoiesis in normal individuals as well as pre-leukemic and leukemic stem cells in patients during the natural course of hematopoietic malignancies and following treatment. Through these research directions we aim to identify novel therapeutic strategies towards regenerative hematopoiesis and targeting of leukemic stem cells.