Sten Eirik W. Jacobsen Lab (Hematopoietic Stem Cell Biology Group)
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.
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.
Eva Hellström Lindberg, Department of Medicine, Huddinge
Sten Linnarsson, Department of Medical Biochemistry and Biophysics
Rickard Sandberg, Department of Cell and Molecular Biology
Petter Woll, Department of Medicine, Huddinge
Magnus Tobiasson, Department of Medicine, Huddinge
Seishi Ogawa, Department of Pathology and Tumor Biology, Kyoto University and Karolinska Institutet
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
Marella de Bruijn, 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
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), 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).
- Karolinska Institutet
- Knut and Alice Wallenberg Foundation
- The Swedish Research Council
- Torsten Söderbergs Foundation
- Karolinska Institutet, Center for Innovative Medicine (CIMED)
- The Swedish Cancer Society
- The Swedish Pediatric Cancer Society
- Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors.
Booth CAG, Barkas N, Neo WH, Boukarabila H, Soilleux EJ, Giotopoulos G, Farnoud N, Giustacchini A, Ashley N, Carrelha J, Jamieson L, Atkinson D, Bouriez-Jones T, Prinjha RK, Milne TA, Teachey DT, Papaemmanuil E, Huntly BJP, Jacobsen SEW, Mead AJ
Cancer Cell 2018 02;33(2):274-291.e8
- Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells.
Carrelha J, Meng Y, Kettyle LM, Luis TC, Norfo R, Alcolea V, et al
Nature 2018 02;554(7690):106-111, PMID: 29298288
- Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.
Giustacchini A, Thongjuea S, Barkas N, Woll PS, Povinelli BJ, Booth CAG, et al
Nat. Med. 2017 Jun;23(6):692-702, PMID: 28504724
- Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.
Luis TC, Luc S, Mizukami T, Boukarabila H, Thongjuea S, Woll PS, et al
Nat. Immunol. 2016 Dec;17(12):1424-1435, PMID: 27695000
- Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing.
Drissen R, Buza-Vidas N, Woll P, Thongjuea S, Gambardella A, Giustacchini A, et al
Nat. Immunol. 2016 06;17(6):666-676, PMID: 27043410
- Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.
Woll PS, Kjällquist U, Chowdhury O, Doolittle H, Wedge DC, Thongjuea S, et al
Cancer Cell 2014 Jun;25(6):794-808, PMID: 24835589
- Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells.
Böiers C, Carrelha J, Lutteropp M, Luc S, Green JC, Azzoni E, et al
Cell Stem Cell 2013 Nov;13(5):535-48, PMID: 24054998
- Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy.
Sanjuan-Pla A, Macaulay IC, Jensen CT, Woll PS, Luis TC, Mead A, et al
Nature 2013 Oct;502(7470):232-6, PMID: 23934107
- Persistent malignant stem cells in del(5q) myelodysplasia in remission.
Tehranchi R, Woll PS, Anderson K, Buza-Vidas N, Mizukami T, Mead AJ, et al
N. Engl. J. Med. 2010 Sep;363(11):1025-37, PMID: 20825315
- Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment.
Adolfsson J, Månsson R, Buza-Vidas N, Hultquist A, Liuba K, Jensen CT, et al
Cell 2005 Apr;121(2):295-306, PMID: 15851035