Sten Eirik W. Jacobsen group (Haematopoietic Stem Cell Biology Group)
Regulation of normal and malignant hematopoiesis
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.
The long-term goal of the research program of the Jacobsen laboratory is to unravel the normal cellular pathways of lineage commitment from hematopoietic stem cells to lineage-restricted progenitors, during embryonic development as well as in adult hematopoiesis. This knowledge is applied towards also obtaining a better understanding of the key molecular determinants of normal lineage commitment.
Moreover, it forms the basis for modeling the impact of collaborating mutations at distinct stages of lineage commitment, and to identify key molecular events in the transformation from normal to malignant hematopoiesis. This work is complemented by tracking the fate and genetic evolution of pre-leukemic and leukemic stem cells in patients during the natural course of hematopoietic malignancies and following treatment. Through these research directions we expect to identify improved therapeutic approaches towards regenerative hematopoiesis and novel therapies more efficiently targeting leukemic stem cells.
Sten Eirik W. Jacobsen, M.D. Ph.D., Professor, Group Leader
Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.
Nat. Immunol. 2016 Dec;17(12):1424-1435
Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing.
Nat. Immunol. 2016 Jun;17(6):666-76
A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.
Nat. Cell Biol. 2016 Feb;18(2):157-67
Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.
Cancer Cell 2014 Jun;25(6):794-808
Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy.
Nature 2013 Oct;502(7470):232-6
Germline JAK2 mutation in a family with hereditary thrombocytosis.
N. Engl. J. Med. 2012 Mar;366(10):967-9
The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential.
Nat. Immunol. 2012 Feb;13(4):412-9
Persistent malignant stem cells in del(5q) myelodysplasia in remission.
N. Engl. J. Med. 2010 Sep;363(11):1025-37
Cited2 is an essential regulator of adult hematopoietic stem cells.
Cell Stem Cell 2009 Dec;5(6):659-65