Sten Eirik W. Jacobsen's group
Unraveling normal and malignant hematopoietic stem and progenitor cell biology at the single cell level.
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; Carrelha Nature 2018). 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 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.
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
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