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Jacobsen Group: Haematopoietic Stem Cell Biology

Research in the Jacobsen group is focused at unravelling 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; Meng Nature Cell Biology 2023; Belander Strålin Cell Research 2023). 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; Ali Nature Biotechnology 2022; Giannakopoulou Nature Cancer 2023; Rodriguez-Meira Nature Genetics 2023; Dimitriou Blood 2023) and myeloproliferative neoplasms (Mead N Engl J Med 2012; Giustacchini  Nature Medicine 2017).

The current focus of the research program of the Jacobsen group is to apply different genetic tools and functional as well as molecular single cell analysis to unravel the dynamics of distinct 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 genomic 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 genomic 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 Department of Medicine, Huddinge and at the Department of Cell and Molecular Biology.

Our team

Featured Publications

Funding

Biotechnology and Biological Sciences Research Council (BBSRC) 

Medical Research Council (MRC) UK

The Swedish Research Council

The Swedish Cancer Society 

Related research themes

We seek to understand the causes of diseases of the blood and other malignancies, from a molecular to systems level, with a focus on blood cancers, rare inherited conditions and the tumour microenvironment. We use and develop innovative techniques to drive research in this area, and are committed to bringing about change in clinical diagnosis and practice. Our pathologists discovered many of the biomarkers now used routinely in clinical practice, translate laboratory findings into clinical tests and are developing digital pathology initiatives.
Haematology and Pathology
Our research is focused on both blood cancers (myeloid and lymphoid malignancies) and solid tumours, such as breast, colorectal, endocrine and lung cancers, with a number of drug discovery efforts and clinical trials taking place within the department. By understanding the basic biology and underlying disease mechanisms we aim to find effective new biomarkers and treatment approaches.
Cancer Biology
Understanding the fundamental biology that drives embryonic development and tissue maintenance provides the basis of much of our research into blood diseases, the cardiovascular system and rare genetic conditions.
Stem Cells and Developmental Biology
A raft of cellular and molecular biology techniques underpin much of the work we do to elucidate the mechanisms of disease. We use established techniques to answer new questions and also develop our own novel and unique methodologies to drive further innovation.
Cellular and Molecular Biology
Employing a range of genetic techniques, we probe the fundamental causes of disease. Our expertise spans identification of causative genes in rare inherited diseases, through to elucidating complex gene regulatory pathways and exploration of susceptibility to common disease through genome-wide association studies. We use cutting edge techniques to manipulate the genome to determine how particular genes work and study how variants in regulatory DNA may contribute to common disease. An important overall aim is to improve the management of human genetic diseases.
Genetics, Genomics and Genome Biology
We have cutting edge expertise in a range of statistical and mathematical modelling techniques that allow us to interrogate large data sets – from the ‘big data’ of genomics through to magnetic resonance imaging and clinical trials. We are also home to the Medical Research Council WIMM Centre for Computational Biology – a hub for accelerating progress in genomics analysis and single cell biology.
Computational Biology, Statistics and Bioinformatics