Sebastian Lewandowski

Sebastian Lewandowski

Senior Research Specialist
Visiting address: CMM, Visionsgatan 18, 5 tr, 17176 Stockholm
Postal address: K8 Klinisk neurovetenskap, K8 Neuro Harris Lewandowski, 171 77 Stockholm
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About me

  • 2018 - ongoing - Team Leader at the Department of Clinical Neuroscience and Center for Molecular Medicine
    2008 - 2018 - Postdoc. Ulf Eriksson group, Karolinska Institutet
    2005 - PhD degree. Nencki Institute of Experimental Biology, Warsaw, Poland
    1997 - MSc degree. University of Gdansk, Poland

Research

  • Our team studies cellular mechanisms of cerebrovascular injury mechanisms in ALS neurodegeneration to find novel clinical biomarkers and therapeutic solutions.

    Publication highlight:
    Månberg A. et al. Nature Medicine, April 2021
    "Altered perivascular fibroblast activity precedes ALS disease onset".

    Nature Medicine News and Views, April 2021
    "Is presymptomatic ALS perivascular?"

    Karolinska Institute Press release.
    "New type of cell contributes to increased understanding of ALS"

    Our web resource for cell-specific gene expression in ALS:
    https://alscellatlas.org/

    We look at how blood vessel dysfunction and vascular remodelling lead to
    increased severity of Amyotrophic Lateral Sclerosis (ALS) and FTD using
    bioinformatics, in-vivo rodent models and clinical samples. We collaborate
    with the leading neurology centres in Europe and US including UZ Leuven in
    Belgium, Univ. Utrecht in Holland, Ulm Univ. in Germany and UCSD in San
    Diego. Our results lead to novel off-label drug applications to therapy and
    biomarkers in neurodegeneration including ALS, stroke and multiple sclerosis.

    We offer Master student, PhD and Postdoc positions to highly motivated and 
    enthusiastic researchers. For details, send an email to sebastian.lewandowski@ki.se

Teaching

  • 2020 - ongoing - PhD course director "The Vascular Brain"  
    2008 - ongoing - Lecturer and group discussion leader in the Biomedicine program
    2018 - ongoing - MSc student supervision 

Articles

All other publications

Grants

  • Karolinska Institutet
    1 January 2024 - 1 January 2028
    Brain scar formation in acute injury and chronic neurodegeneration leads to permanent lesions with dramatic consequences for individual patients and healthcare systems. Previous work has described the scar- forming contributions from glial and infiltrating immune cells. Yet, recent findings challenged this notion and showed that the lesion core is formed by a newly discovered cell type - the brain perivascular fibroblast with glial cells surrounding the injury area. Single cell RNA data suggests that fibroblasts enlarge perivascular space during injury and secrete chemokines facilitating immune cell infiltration. However, without functional interventions in-vivo we still will not understand how the fibroblasts contribute to the newly formed lesions and how they interact with the immune system. We propose to examine the role of the fibroblasts in the brain injury response by examining their contribution to vascular remodeling and immune cell infiltration in an acute model of the BBB opening (Dorian McGavern at NIH) and in ALS neurodegeneration (Sebastian Lewandowski at Karolinska Institute). We propose to deplete the brain fibroblast cells using a recombinant diphtheria toxin. We will first use this approach to examine their role in a brain injury response using an acute model of blood-brain barrier (BBB) opening with focal ultrasound developed by the host lab (Mastorakos et al. Nature 1 Neuroscience 2021) . Finally, since our previous studies showed that the brain fibroblasts are activated in early stages of ALS (Månberg et al. Nature Medicine 2021)2, we will also deplete these cells in a mouse model of ALS to examine their effect on immune infiltration and disease dynamics (see Fig. 1). Completion of the proposed project will allow us to determine how fibroblasts contribute to brain repair versus neurodegeneration. By comparing the contributions of fibroblasts to these two different outcomes, we aim to identify fibroblast programs that may lead to CNS repair therapies.
  • Swedish Research Council
    1 January 2022 - 31 December 2024
  • Swedish Brain Foundation
    1 January 2022 - 1 January 2024
  • Molecular phenotyping of brain metabolism in asymptomatic ALS/FTD patients
    Karolinska Institutet
    1 January 2022 - 1 January 2024

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