Jakob Michaëlsson

Jakob Michaëlsson

Principal Researcher | Docent
Visiting address: Alfred Nobels allé 8, plan 7, 14152 Huddinge
Postal address: H7 Medicin, Huddinge, H7 CIM Michaelsson, 171 77 Stockholm
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About me

  • Jakob Michaëlsson is the group leader of the Michaelsson research group at the at the Center for Infectious Medicine (CIM) at the Department of Medicine Huddinge. He received his PhD at Karolinska Institutet in 2002 studying Natural Killer (NK) cell biology and after a postdoc at the University of California San Francisco where he continued his research in human immunology he has been a group leader at CIM since 2008. His research includes studies of human immune cell development, immune regulation and immune responses to cancer, with a particular focus on NK cells, ILCs, and CD8+ T cells. 

    https://ki.se/en/medh/jakob-michaelsson-group

Research

  • The main focus of our research is to understand how human Natural Killer (NK) cells, ILCs, and CD8 T cells develop and function during different stages of life, in different tissues, and during different conditions. The longterm goal with our research is to aid in the development of new therapies in cancer and infectious diseases. We have a strong competence in advanced flow cytometry analysis of human immune cells in blood and tissues, paired with RNA sequencing and functional in vitro assays. 

    Development of human innate lymphoid cells in fetal tissues

    Little is known about how and where human immune cells develop and mature, and what signals are regulating innate lymphoid cell (ILC) development, including NK cells. We have previously investigated the development and function of fetal NK cells and T cells in the developing fetus, demonstrating that they are phenotypically and functionally distinct from those in adults. Within this project we are currently aiming at elucidating the developmental trajectories of human fetal ILCs from precursor stages to mature cells, and to investigate how fetal ILCs compare to adult ILCs in various human tissues.
    We believe that this project will provide important knowledge regarding the development of the human immune system, which could have implications in for example in utero therapies and for our understanding of immune responses in new born babies.

    Tissue-resident NK cells in the human lung and lung tumors

    Most of our knowledge regarding human NK cell biology is based on studies of these cells in peripheral blood. Recently it has becoming increasingly clear that NK cells in tissues differ from those in tissues, with distinct phenotypes, function and possibly developmental origins. In this project we focus on the biology of tissue-resident NK cells in the human lung and what role they might play lung tumors. The project is a collaboration with 

    Team Marquardt at The Center for Hematology and Regenerative Medicine (HERM) in Neo.

    Formation of the human memory CD8+ T cell repertoire at the clonal level

    CD8+ T cells play an important role in our defense against viral infections and tumors. It is well known that antigen-specific CD8+ T cells expand in viral infections and eventually form a broad repertoire of memory CD8+ T cells that can help in protecting against subsequent infections with the same virus. In this project we collaborate with Dr Jeff Mold and the Frisén lab to investigate how the repertoire of memory CD8+ T cells is shaped by distinct clonal identities over time in response to vaccination against Yellow Fever virus.

Articles

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Grants

  • Swedish Research Council
    1 January 2025 - 31 December 2028
    Innate lymphoid cells (ILC), including NK cells, ILC1, ILC2, and ILC3, are involved in lymphoid tissue-development, infections, cancer, inflammation and tissue-repair. We have recently shown that ILCs develop early, with distinct distribution and gene expression depending on tissue. In this application we will investigate the development and diversity of human fetal ILCs and their progenitors at clonal level. We hypothesize that development from tissue-restricted ILC progenitors together with clonally heritable gene expression and the tissue environment shape the development and diversity of human ILCs across tissues. By analyzing somatic mutations in mitochondrial genes, coupled with gene and protein expression at single cell level we aim at performing lineage tracing based on mutational patterns in human fetal ILC across tissues. To verify the results from the in vivo fate mapping data and to gain further insight into ILC development, we will dissect the potential of individual CD34+ HPCs to differentiate to mature ILCs in vitro. Finally, we aim at determining clonally heritable gene expression (clonal memory) in ILCs, enabling us to assess to what extent clonal memory contributes to tissue-dependent differences, as well as to dissect gene expression regulation in ILCs. We believe that the proposed project is important for a better basic understanding of human fetal hematopoiesis, as well as for tissue-specific immunity and hematopoietic stem cell-based therapies.
  • Dissecting human ILC development and differentiation at the clonal level
    Swedish Research Council
    1 January 2025 - 31 December 2028
  • Dissecting the functional regulation of lung tumor-infiltrating human NK Cells
    Swedish Cancer Society
    1 January 2024 - 31 December 2026
  • Swedish Research Council
    1 January 2021 - 31 December 2024
  • Swedish Research Council
    1 January 2017 - 31 December 2020

Employments

  • Principal Researcher, Department of Medicine, Huddinge, Karolinska Institutet, 2022-

Degrees and Education

  • Docent, Karolinska Institutet, 2015
  • Doctor Of Philosophy, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 2002

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