Hematopoietic Stem Cell Biology Group – Sten Eirik W. Jacobsen Lab

The group's focus is to unravel normal and malignant hematopoietic stem and progenitor cell biology at the single cell level. The research group aims to understand how normal blood cell formation from stem cells in the bone marrow is organized and regulated and on how normal stem cells are transformed into malignant stem cells.

A group of people.

About our research

Our research is focused at understanding how normal blood cell formation from stem cells in the bone marrow is organized and regulated to ensure replenishment of millions of blood cells per second, and on how normal stem cells upon acquisition of oncogenic mutations are transformed into malignant stem cells. The Jacobsen Group has demonstrated that the bone marrow contains different normal blood forming stem cells with different functions. We have also identified and characterized the cancer stem cells in different blood malignancies and demonstrated that these are resistant to different types of standard treatments and responsible for the relapse of the disease after otherwise successful therapy.

The goal of The Jacobsen Group’s research program is to identify new and more efficient therapies. We do that in part through stimulation of normal stem cells to enhance normal blood cell replenishment in patients in who blood formation is defective. In part it's also by developing treatments that more specifically target and eliminate the cancer stem cells towards curative treatments in blood cell malignancies.

The Jacobsen Group’s research program is in part pursued at the Haematopoietic Stem Cell Biology Laboratory, MRC Molecular Haematolgy Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Current research focus

The current research focus of the Jacobsen Group is to apply different genetic tools and functional, as well as molecular single cell analysis. The aim is to unravel the dynamics of stem and progenitor cells in unperturbed hematopoiesis, as well as in response to distinct challenges, in mice and normal human subjects. We also study in patients and model in mice the impact of recurrent genetic lesions at distinct stages of hematopoietic lineage commitment. This is to unravel key cellular targets and molecular events in the transformation from normal to malignant hematopoiesis. The goal is identifying novel cellular and molecular therapeutic targets. Through these research directions we aim to identify novel therapeutic strategies towards regenerative hematopoiesis and targeting of leukemic stem cells.

Collaborations

Karolinska Institutet

International collaboration

  • Adam Mead, MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital University of Oxford
  • Claus Nerlov, MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital University of Oxford
  • Johanna Olweus, Department of Cancer Immunology, Oslo University Hospital
  • Seishi Ogawa, Department of Pathology and Tumor Biology, Kyoto University

Projects

Unravelling normal and malignant hematopoietic stem and progenitor cell biology at the single cell level

The Jacobsen Group 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 2005Boiers Cell Stem Cell 2013Sanjuan-Pla Nature 2013Luis Nature Immunology 2016Drissen Nature Immunology 2016Carrelha Nature 2018, Meng Nature Cell Biology 2023, Belander Strålin Cell Research 2023), and identified and characterized distinct and rare cancer stem cells and their therapeutic resistance in chronic hematological malignancies (Tehranchi New Engl J Med 2010Mead N Engl J Med 2012Woll Cancer Cell 2014Giustacchini Nature Medicine 2017, Ali Nature Biotechnology 2022, Giannakopoulou Nature Cancer 2023, Rodriguez-Meira Nature Genetics 2023, Dimitriou Blood 2023, in press).

Publications

Selected publications

Funding

  • Karolinska Institutet
  • Knut and Alice Wallenberg Foundation
  • The Swedish Research Council
  • Torsten Söderbergs Foundation
  • The Swedish Cancer Society
  • The Swedish Pediatric Cancer Society
  • Karolinska Institutet, Strategic Research Area (SRA), Stem Cells and Regenerative Medicine, Department of Medicine, Huddinge

Staff and contact

Group leader

All members of the group