Sten Eirik W. Jacobsen's group

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

A group of people.
Sten Eirik W. Jacobsen's research group. Photo: Stefan Zimmerman

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 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 2018Meng Nature Cell Biology 2023Belander 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 2017Ali Nature Biotechnology 2022Giannakopoulou Nature Cancer 2023Rodriguez-Meira Nature Genetics 2023, Dimitriou Blood 2023, in press).

The current focus of the research program of the Jacobsen lab is to apply different genetic tools and functional as well as molecular single cell analysis to unravel the dynamics of 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 genetic 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 genetic 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.

The Jacobsen Group’s research program is in part pursued in his laboratory at the Karolinska Institute, Sweden at the Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge and at Haematopoietic Stem Cell Biology Laboratory, MRC Molecular HaematolgyUnit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine University of Oxford, Oxford, UK.

Group Members

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Sten Eirik Jacobsen

M.D. Ph.D., Professor, Group Leader
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Dimitra Vasileiadi

M.Sc., Research Administrator/ Personal Assistant
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Kari Högstrand

Ph.D., Senior Lab Manager

Masafumi Seki

M.D., Post doc

Selected publications

Link to all publications (PubMed)

A T cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo.
Giannakopoulou E, Lehander M, Virding Culleton S, Yang W, Li Y, Karpanen T, Yoshizato T, Rustad EH, Nielsen MM, Bollineni RC, Tran TT, Delic-Sarac M, Gjerdingen TJ, Douvlataniotis K, Laos M, Ali M, Hillen A, Mazzi S, Chin DWL, Mehta A, Holm JS, Bentzen AK, Bill M, Griffioen M, Gedde-Dahl T, Lehmann S, Jacobsen SEW, Woll PS, Olweus J
Nat Cancer 2023 Oct;4(10):1474-1490

Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution.
Rodriguez-Meira A, Norfo R, Wen S, Chédeville AL, Rahman H, O'Sullivan J, Wang G, Louka E, Kretzschmar WW, Paterson A, Brierley C, Martin JE, Demeule C, Bashton M, Sousos N, Moralli D, Subha Meem L, Carrelha J, Wu B, Hamblin A, Guermouche H, Pasquier F, Marzac C, Girodon F, Vainchenker W, Drummond M, Harrison C, Chapman JR, Plo I, Jacobsen SEW, Psaila B, Thongjuea S, Antony-Debré I, Mead AJ
Nat Genet 2023 Sep;55(9):1531-1541

Platelet and myeloid lineage biases of transplanted single perinatal mouse hematopoietic stem cells.
Belander Strålin K, Carrelha J, Winroth A, Ziegenhain C, Hagemann-Jensen M, Kettyle LM, Hillen A, Högstrand K, Markljung E, Grasso F, Seki M, Mazzi S, Meng Y, Wu B, Chari E, Lehander M, Sandberg R, Woll PS, Jacobsen SEW
Cell Res 2023 Nov;33(11):883-886

T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes.
Ali M, Giannakopoulou E, Li Y, Lehander M, Virding Culleton S, Yang W, Knetter C, Odabasi MC, Bollineni RC, Yang X, Foldvari Z, Böschen ML, Taraldsrud E, Strønen E, Toebes M, Hillen A, Mazzi S, de Ru AH, Janssen GMC, Kolstad A, Tjønnfjord GE, Lie BA, Griffioen M, Lehmann S, Osnes LT, Buechner J, Garcia KC, Schumacher TN, van Veelen PA, Leisegang M, Jacobsen SEW, Woll P, Olweus J
Nat Biotechnol 2022 04;40(4):488-498

Loss of endothelial membrane KIT ligand affects systemic KIT ligand levels but not bone marrow hematopoietic stem cells.
Matsuoka S, Facchini R, Luis TC, Carrelha J, Woll PS, Mizukami T, Wu B, Boukarabila H, Buono M, Norfo R, Arai F, Suda T, Mead AJ, Nerlov C, Jacobsen SEW
Blood 2023 Nov;142(19):1622-1632

Identification and surveillance of rare relapse-initiating stem cells during complete remission post-transplantation.
Dimitriou M, Mortera-Blanco T, Tobiasson M, Mazzi S, Lehander M, Högstrand K, Karimi M, Walldin G, Jansson M, Vonlanthen S, Ljungman P, Langemeijer S, Yoshizato T, Hellström-Lindberg E, Woll PS, Jacobsen SE#
Blood, in press.

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

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, et al
Cancer Cell 2018 02;33(2):274-291.e8

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

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

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

Content reviewer:
Linda Lindell