Curriculum Vitae s277

WIMM PI

Curriculum Vitae

Personal Data

Name Sten Eirik W. Jacobsen

Nationality Norwegian

Email

Present Position

July 2015-date: Professor in Stem Cell Biology and Regenerative Medicine, Department of Cell and Molecular Biology, Department of Medicine Huddinge, and Clinical Unit of Hematology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

July 2015-date: Guest Professor in Stem Cell Biology and Regenerative Medicine, Haematopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford.

Previous Positions

2010-2015: Guest Professor Karolinska Institutet, Stockholm, Sweden

July 2006-June 2015: Anne T and Robert M Bass Professorship of Developmental and Stem Cell Biology as applied to Medicine, Haematopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford. Endowed chair and permanant position.

2003-2007: Founding and Acting Director, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy

2000-2007: Professor, Hematopoietic Stem Cell Laboratory, Lund University, Sweden

1998-2004: Senior scientist position Swedish Cancer Society

1996-2007: Senior consultant physician, Department of Hematology, Lund University Hospital

1996-2000: Associate Professor, Department of Internal Medicine, University of Lund, Sweden

1995-1997: Adjunct Associate Professor of Medicine, Wright State University, Dayton, Ohio, USA

1995-1997: Adjunct Asscociate Professor of Immunology, Wright State University, Dayton, Ohio, USA

1994: Norwegian Cancer Society Senior Scientist at the Department of Immunology, the Norwegian Radium Hospital.

1994-1996: Head, Blood Cell Growth Factors Laboratory, Hipple Cancer Research Center, Dayton, Ohio, U.S.A.

Lay Summary of Research Programme

Hematology provided the first definitive proof for successful regenerative medicine, first through bone marrow transplantation as a cell replacement therapy, and next through identification of key regulatory molecules, such as erythropoietin, which are used to enhance replenishment of specific blood cell lineages in demand. Despite of this, only a small fraction of the full potential of hematological regenerative medicine has been realized. Through our studies in mouse and man, aiming to obtain a better understanding of the normal cellular pathways for generation and regeneration of essential blood cell lineages, and efforts to unravel the molecular regulation of these blood lineage pathways, we hope to expand and improve the cellular and molecular approaches towards hematological regenerative medicine. Likewise, through our studies aiming to better understand the identity of the stem cells of hematological malignancies, and myelodysplastic syndromes in particular, as well as through identification of key molecular pathways dysregulated in these malignant stem cells, we expect to identify and explore better cellular and molecular targets for therapeutic interventions.

Publications 2007-2016

Anderson K, Rusterholz C, Månsson R, Jensen CT, Bacos K, Zandi S, Sasaki Y, Sigvardsson M, Jacobsen SE. Ectopic expression of PAX5 promotes self-renewal of biphenotypic myeloid progenitors co-expressing myeloid and B-cell lineage-associated genes. Blood 2007 May 1;109(9):3697-705. PMID:17218387

Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, Fries JW, Tiemann K, Bohlen H, Hescheler J, Welz A, Bloch W, Jacobsen SE, Fleischmann BK. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 2007 Aug 15;110(4):1362-9. PMID:17483296

Buza-Vidas N, Cheng M, Duarte S, Nozad H, Jacobsen SE#*, Sitnicka E*. Crucial role of FLT3 ligand in immune reconstitution following bone marrow transplantation and high-dose chemotherapy. Blood 2007 Jul 1;110(1):424-32. (*equal contribution, #corresponding author) PMID:17379745

Buza-Vidas N, Luc S, Jacobsen SE. Delineation of the earliest lineage commitment steps of haematopoietic stem cells: new developments, controversies and major challenges. Curr Opin Hematol. 2007 Jul;14(4):315-21. PMID:17534155

Fujimoto T, Anderson K, Jacobsen SE, Nishikawa S-I, Nerlov C. Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction. EMBO J 2007 May 2;26(9):2361-70. PMID:17431401

Grövdal M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Wallvik J, Tangen JM, Oberg G, Jacobsen SE, Hokland P, Porwit A, Hellström-Lindberg E. Negative Effect of DNA Hypermethylation on the Outcome of Intensive Chemotherapy in Older Patients with High-Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia following Myelodysplastic Syndrome. Clin Cancer Res. 2007 Dec 1;13(23):7107-12. PMID: 18056190

Jensen CT, Kharazi S, Böiers C, Liuba K, Jacobsen SE. TSLP-mediated fetal B lymphopoiesis? Nat Immunol. 2007 Sep;8(9):897. PMID:17712336

Lee BH, Tothova Z, Levine RL, Anderson K, Buza-Vidas N, Cullen DE, McDowell EP, Adelsperger J, Fröhling S, Huntly BJP, Beran M, Jacobsen SE, Gilliland DG. FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia. Cancer Cell 2007 Oct;12(4):367-80. PMID:17936561

Luc S, Buza-Vidas N, Jacobsen SE. Biological and molecular evidence for existence of lymphoid-primed multipotent progenitors. Ann N Y Acad Sci. 2007 Jun;1106:89-94. PMID:17442777

Månsson R*, Hultquist A*, Luc S*, Yang L*, Anderson K, Kharazi S, Al-Hashmi S, Liuba K, Thorén L, Adolfsson J, Buza-Vidas N, Qian H, Soneji S, Enver T, Sigvardsson M, Jacobsen SE. Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors. Immunity 2007 Apr;26(4):407-19. (* equal contribution) (cover article). PMID: 17433729

Nilsson L, Edén P, Olsson E, Månsson R, Åstrand-Grundström I, Strömbeck B, Theilgaard-Moench K, Anderson K, Hast R, Hellström-Lindberg E, Samuelsson J, Bergh G, Nerlov C, Johansson B, Sigvardsson M, Borg A, Jacobsen SE. The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes. Blood 2007 Oct 15;110(8):3005-14. PMID:17616640

Pfenninger CV, Roschupkina T, Hertwig F, Kottwitz D, Englund E, Bengzon J, Jacobsen SE, Nuber UA. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells. Cancer Research 2007 Jun 15;67(12):5727-36. PMID:17575139

Qian H, Buza-Vidas N, Hyland C, Jensen C, Antonchuk J, Mansson R, Thoren L, Ekblom M, Alexander W, Jacobsen SE. Critical role of thrombopoietin in maintaining postnatal quiescent hematopoietic stem cells. Cell Stem Cell 2007 Dec 13;1(6):671-84. PMID:18371408

Qian H, Georges-Labouesse E, Nyström A, Domogatskaya A, Tryggvason K, Jacobsen SE, Ekblom M. Distinct roles of integrins alpha6 and alpha4 in homing of fetal liver hematopoietic stem and progenitor cells. Blood 2007 Oct 1;110(7):2399-407. PMID:17586725

Sitnicka E, Buza-Vidas N, Ahlenius H, Cilio CM, Gekas C, Nygren JM, Mansson R, Cheng M, Jensen CT, Svensson M, Leandersson K, Agace WW, Sigvardsson M, Jacobsen SE. Critical role of FLT3 ligand in IL-7 receptor-independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors. Blood 2007 Oct 15;110(8):2955-64. PMID:17540845

Buitenhuis M, Verhagen LP, Van Deutekom HWM, Castor A, Verploegen S, Koenderman L, Jacobsen SE, Coffer PJ. Protein kinase B (C-Akt) regulates hematopoietic lineage choice decisions during myelopoiesis. Blood. 2008 Jan 1;111(1):112-21. PMID:17890457

Hansson F, Toporski J, Mansson R, Johansson B, Noren-Nystrom U, Jacobsen SE, Wiebe T, Larsson M, Sigvardsson M, Castor A. Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression. Mol Cancer. 2008 Aug 11,7:67. PMID:18694513

Jensen CT, Boiers C, Kharazi S, Lubking A, Rydén T, Sigvardsson M, Sitnicka E, Jacobsen SE. Permissive Roles of Hematopoietin and Cytokine Tyrosine Kinase Receptors in Early T-Cell Development. Blood 2008 Feb 15;111(4):2083-90. PMID:18039955

Jensen CT, Kharazi S, Böiers C, Cheng M, Lübking A, Sitnicka E, Jacobsen SE. FLT3 ligand and not TSLP is the key regulator of IL-7-independent B-1 and B-2 B lymphopoiesis. Blood 2008 Sep 15;112(6):2297-304. PMID:18566323

Kirstetter P, Schuster MB, Bereshchenko O, Moore S, DvingeH, Kurz E, Theilgaard-Mönch K, MånssonR , PedersenTA, Pabst T, Schrock E, Porse BT, Jacobsen SE, Bertone P, Tenen D, Nerlov C. Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. Cancer Cell (Cell Press) 2008 Apr;13(4):299-310. PMID:18394553

Luc S, Anderson K, Kharazi S, Buza-Vidas N, Böiers C, Jensen CT, Ma Z, Wittman L, and Jacobsen SE. Down-regulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential. Blood 2008 Apr 1;111(7):3424-34. PMID:18218856

Luc S, Buza-Vidas N, Jacobsen SE. Delineating the cellular pathways of hematopoietic lineage commitment. Semin Immunol 2008 Aug;20(4):213-20. PMID:18752972

Mansson R, Zandi S, Andersson K, Martensson IL, Jacobsen SE, Bryder D, Sigvardsson M. B-lineage commitment prior to surface expression of B220 and CD19 on hematopoietic progenitor cells. Blood 2008 Aug 15,112(4):1048-55. PMID:18495958

Nygren JM, Liuba K, Breitbach M, Stott S, Thoren L, Roell W, Geisen C, Sasse P, Kirik D, Björklund A, Nerlov C, Fleischmann BK, Jovinge S, Jacobsen SE. Myeloid and lymphoid contribution to non-hematopoietic cell lineages through irradiation-induced heterotypic cell fusion. Nature Cell Biology 2008 May;10(5):584-92. PMID:18425115

Svensson M, Marsal J, Uronen-Hansson H, Chenh M, Jenkinson W, Cilio C, Jacobsen SE, Sitnicka E, Anderson G, Agace WW. Involvement of CCR9 at multiple stages of adult T lymphopoiesis. J Leukoc Biol. 2008 Jan;83(1):156-64. PMID:17911179

Thoren L, Liuba K, Bryder D, Nygren J, Jensen CT, Qian H, Antonchuk J, Jacobsen SE. Kit Regulates Maintenance of quiescent hematopoietic stem cells. J Immunol 2008 Feb 15;180(4):2045-53. PMID:18250409

Weischenfeldt1 J, Damgaard I, Bryder D, Theilgaard-Mönch K, Thoren LA, Nielsen CF, Jacobsen SE, Nerlov C, PorseCT. NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements. Genes and Development 2008 May 15;22(10):1381-96. PMID:18483223

Bereshchenko O, Mancini E, Moore S, Bilbao D, Mansson R, Luc S, Grover A, Jacobsen SE, Bryder D, Nerlov C. Hematopoietic stem cell expansion precedes the generation of committed myeloid leukemia-initiating cells in C/EBPalpha mutant AML. Cancer Cell (Cell Press) 2009 Nov 6,16(5):390-400. PMID:19878871

Bröske AM, Vockentanz L, Kharazi S, Huska M, Mancini E, Scheller M, Enns A, Prinz M, Jaenisch R, Nerlov C, Leutz A, Andrade-Navarro MA, Jacobsen SE, Rosenbauer F. DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.. Nature Genetics 2009 Nov,41(11):1207-15. PMID:19801979

Buza-Vidas N, Cheng M, Duarte S, Charoudeh HN, Jacobsen SE#* and Sitnicka E*. FLT3 receptor and ligand are dispensable for maintenance and post-transplantation expansion of mouse hematopoietic stem cells. Blood 2009 Apr 9;113(15):3453-60 (*Equal contribution, #corresponding author). PMID:19188666

Cheng M, Charoudeh HN, Brodin P, Tang Y, Lakshmikanth T, Höglund P, Jacobsen SE, Sitnicka E. Distinct and overlapping patterns of cytokine regulation of thymic and bone marrow-derived NK cell development. J Immunol. 2009 Feb 1;182(3):1460-8. PMID:19155493

Enver T, Jacobsen SE. Developmental biology: Instructions writ in blood. Nature 2009 Sep 10; 461(7261):183-4. PMID:19741696

Kranc KR, Schepers H, Rodrigues N, Bamforth S, Villadsen E, Ferry H, Bouriez-Jones T, Sigvardsson M, Bhattacharya S, Jacobsen SE*, Enver T*. Cited2 is an essential regulator of adult hematopoietic stem cells. Cell Stem Cell (Cell Press), 2009 Dec 4,5(6):659-65 (*Equal senior contribution). PMID:19951693

Liuba K, Pronk CJH, Stott SRW and Jacobsen SE. Polyclonal T-cell reconstitution of X-SCID recipients following in utero transplantation of lymphoid-primed multipotent progenitors. Blood 2009 May 7,113(19):4790-8. PMID:19074736

Thored P, Heldmann U, Gomes-Leal W, Gisler R, Darsalia V, Taneera J, Nygren JM, Jacobsen SE, Ekdahl CT, Kokaia Z, Lindvall O. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia 2009 Jun;57(8):835-49. PMID:19053043

Tipping AJ, Pina C, Castor A, Hong D, Rodrigues NP, Lazzari L, May GE, Jacobsen SE, Enver T. High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function via effects on cell cycle. Blood 2009 Mar 19;113(12):2661-72. PMID:19168794

Tormin A, Brune JC, Olsson E, Valcich J, Neuman U, Olofsson T, Jacobsen SE, Scheding S. Characterization of bone marrow-derived mesenchymal stromal cells (MSC) based on gene expression profiling of functionally defined MSC subsets. Cytotherapy 2009;118(2):114-28. PMID:19242838

Böiers C, Buza-Vidas N, Jensen CT, Pronk CJ, Kharazi S, Wittmann L, Sitnicka E, Hultquist A, Jacobsen SE. Expression and role of FLT3 in regulation of the earliest stage of normal granulocyte-monocyte progenitor development. Blood 2010 Jun 17,115(24):5061-8. PMID:20393130

Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug,150(3):293-302. PMID:20497178

Nozad Charoudeh H, Tang Y, Cheng M, Cilio CM, Jacobsen SE, Sitnicka E. Identification of a NK/T cell-restricted progenitor in adult bone marrow contributing to bone marrow and thymic-dependent NK cells. Blood 2010 Jul 15,116(2):183-92. PMID:20421450

Tehranchi R, Woll PS, Anderson K, Buza-Vidas N, Mizukami T, Mead AJ, Astrand-Grundström I, Strömbeck B, Horvat A, Ferry H, Dhanda RS, Hast R, Rydén T, Vyas P, Göhring G, Schlegelberger B, Johansson B, Hellström-Lindberg E, List A, Nilsson L, Jacobsen SE. Persistent malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med 2010 Sep 9;363(11):1025-37. PMID:20825315

Buza-Vidas N, Duarte S, Bouriez-Jones T, Ferry H, Hultquist A, Luc S, Jacobsen SE. FLT3 expression initiates in fully multipotent hematopoietic progenitor cells. Blood. 2011 Aug 11; 118(6):1544-8. PMID:21628405

Buza-Vidas N, Duarte S, Luc S, Bouriez-Jones T, Woll PS, Jacobsen SE. GATA3 is redundant for maintenance and self-renewal of hematopoietic stem cells. Blood 2011 Aug 4;118(5):1291-3. PMID:21670475

Chau YY, Brownstein D, Mjoseng H, Lee WC, Buza-Vidas N, Nerlov C, Jacobsen SE, Perry P, Berry R, Thornburn A, Sexton D, Morton N, Hohenstein P, Freyer E, Samuel K, van't Hof R, Hastie N. Acute multiple organ failure in adult mice deleted for the developmental regulator Wt1. PLoS Genet. 2011 Dec;7(12):e1002404. PMID:22216009

De Gobbi M, Garrick D, Lynch M, Vernimmen D, Hughes JR, Goardon N, Luc S, Lower KM, Sloane-Stanley JA, Pina C, Soneji S, Renella R, Enver T, Taylor S, Jacobsen SE, Vyas P, Gibbons RJ, Higgs DR. Generation of Bivalent Chromatin Domains During Cell Fate Decisions. Epigenetics Chromatin, 2011 Jun 6;4(1):9. PMID:21645363

Goardon N, Marchi E, Atzberger A, Quek L, Schuh A, Soneji S, Woll P, Mead A, Alford KA, Rout R, Chaudhury S, Gilkes A, Knapper S, Beldjord K, Begum S, Rose S, Geddes N, Griffiths M, Standen G, Sternberg A, Cavenagh J, Hunter H, Bowen D, Killick S, Robinson L, Price A, Macintyre E, Virgo P, Burnett A, Craddock C, Enver T, Jacobsen SE, Porcher C, Vyas P. Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell. 2011 Jan 18:19(1):138-52. PMID:21251617

Hills D, Gribi R, Ure J, Buza-Vidas N, Luc S, Jacobsen SE, Medvinsky A. Hoxb4-YFP reporter mouse model: a novel tool for tracking HSC development and studying the role of Hoxb4 in hematopoiesis. Blood 2011 Mar 21;117(13):3521-8. PMID:21278354