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.
Article from the Knut and Alice Wallenberg Foundation: "Avslöjar blodbildningens hemligheter" (In Swedish)
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
- Eva Hellström Lindberg, Department of Medicine, Huddinge, KI.
- Petter Woll, Department of Medicine, Huddinge, KI.
- Magnus Tobiasson, Department of Medicine, Huddinge, KI.
- Sten Linnarsson, Department of Medical Biochemistry and Biophysics, KI.
- Rickard Sandberg, Department of Cell and Molecular Biology, KI.
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 2005; Boiers Cell Stem Cell 2013; Sanjuan-Pla Nature 2013; Luis Nature Immunology 2016; Drissen Nature Immunology 2016; Carrelha 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 2010; Mead N Engl J Med 2012; Woll Cancer Cell 2014; Giustacchini Nature Medicine 2017, Ali Nature Biotechnology 2022, Giannakopoulou Nature Cancer 2023, Rodriguez-Meira Nature Genetics 2023, Dimitriou Blood 2023, in press).