Jette Lengefeld

Jette Lengefeld

Assistant Professor
Visiting address: NEO Medicinaren 25, HERM plan 7, Hälsovägen 7C (lastkaj), 14157 Huddinge
Postal address: H7 Medicin, Huddinge, H7 HERM Hellström-Lindberg Lengefeld, 171 77 Stockholm
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About me

  • Jette is a Assistant Professor at HERM - MedH - Karolinska Institutet since 2023 and a group leader at the University of Helsinki (Finland) since 2021. Her research team is investigating how blood stem cells fail to maintain their functions during aging and disease.

    Jette did her graduate studies at the ETH Zurich (Switzerland) focusing on asymmetric cell division in the lab of Yves Barral. Jette performed her postdoctoral studies at MIT (US) in the lab of Angelika Amon, where she discovered cellular enlargement as an aging factor of blood stem cells.

Research

  • The failure to regenerate tissues during aging due to loss of stem cell function causes major health problems. However, it is still unclear how stem cells fail to maintain their functions during aging and disease.

    We discovered a new aspect of stem cell aging in vivo: cellular enlargement. We found that stem cells increase in size during aging and that this is causing their functional decline. However, we are only beginning to understand how size impacts stem cell fitness and the physiological importance of this process remains unsolved.



    Lab webpage: http://lengefeldlab.com


    Selected recent publications:


    1) Davies D, van der Handel K, Bharadwaj S, Lengefeld J†, review
    “Cellular enlargement - a new hallmark of aging?“,
    Frontiers Cell and Developmental Biology (2022)


    2) Padovani F, Mairhörmann B, Falter-Braun P, Lengefeld J, Schmoller KM
    “Segmentation, tracking and cell cycle analysis of live-cell imaging data with Cell-ACDC“
    BMC Biology (2022)


    3) Lengefeld J†, Cheng CW, Maretich P, Blair M, Hagen H, McReynolds MR, Sullivan E, Mayors K, Roberts C, Steiner J, Kang JH, Miettinen TP,
    Manalis SR, Antebi A, Rabinowitz JD, Morrison S, Lees J, Boyer L, Yilmaz O, Amon A
    “Cell size is a determinant of stem cell potential during aging“,
    Science Advances (2021)


    4) Neurohr G, Terry R, Lengefeld J, Bonney M, Brittingham G, Moretto F, Miettinen T, Pontano Vaites L, Soares L, Paulo J, Harper W, Buratowski S, Manalis S, van Werven F, Holt L, Novak B, Tyson J, Amon A†
    “Excessive cell growth causes cytoplasm dilution and contributes to senescence“,
    Cell (2019)

    [1] https://www.frontiersin.org/articles/10.3389/fcell.2022.1036602/full
    [2] https://link.springer.com/article/10.1186/s12915-022-01372-6
    [3] https://www.science.org/doi/10.1126/sciadv.abk0271
    [4] https://pubmed.ncbi.nlm.nih.gov/30739799/

Articles

All other publications

Grants

  • Cancer Foundation Finland
    20 November 2024
  • Academy of Finland
    12 June 2024 - 31 August 2028
    A main contributor to aging is this decline of stem cell function. Despite the essential role of stem cells, we are only beginning to understand the underlying mechanisms. I discovered a new aspect of stem cell aging: cellular enlargement. With age, stem cells increase in size leading to their functional decline. However, it is unclear how size impacts stem cell function. Supported by preliminary data, I hypothesize that enlargement leads to increased distances within stem cells, thereby impairing cellular functions. Using blood stem cells of mouse models, my team will test this hypothesis by (i) identifying how enlargement of stem cells affects distances and (ii) how this affects cellular aging, tissue function and lifespan. The novel concepts outlined here have exceptional potential for scientific impact as they will transform our current understanding of stem cell aging by revealing how enlargement affects fundamental processes of stem cells.
  • European Research Council (ERC) - Starting Grant
    1 January 2024 - 31 December 2028
  • Cancer Foundation Finland
    22 November 2023
  • Swedish Research Council
    1 January 2023 - 31 December 2026
    The failure to regenerate tissues with age underlies some of the most challenging health issues in elderly. A main contributor to this decline is the loss of stem cell function. Despite the essential role of stem cells, how they fail to maintain their functions during ageing and disease is still unclear. I discovered a new aspect of stem cell ageing in vivo: cellular enlargement. With age and damage, stem cells increase in size causing their functional decline. However, how size impacts stem cells fitness and the physiological importance of this process remains unsolved.In my independent lab at the Karolinska Institutet, I will to address these key questions by (1) identifying pathways that cause stem cell dysfunction during age-dependent enlargement and (2) illuminating the effect of stem cell enlargement on cancer.Based on my preliminary data, I hypothesize that enlargement creates a cellular energy deficit, which drives stem cell dysfunction and at the same time prevents their transformation into cancerous cells. Using hematopoietic stem cells of mouse models, my lab will identify the molecular mechanisms impairing fitness of large stem cells by following up on a targeted approach. We will then utilize differently sized, oncogenic stem cells from mice and humans to test their potential to affect leukemia.The novel insights into the molecular mechanisms of size-dependent stem cell fitness and its role in cancer will be of significant scientific and therapeutic value.
  • Academy of Finland
    13 December 2022 - 31 December 2025
    The rapid advancement of stem cell research creates a foundation for future therapeutic strategies spanning from organ replacements to treatment of diabetes and neurodegenerative disease, and to aging-related frailty and disease. To fully realize the potential of stem cell based strategies, we must first understand the cellular processes critical for stem cell function. We have discovered that metabolism is a potent driver of stem cell fate and that metabolic interventions can guide stem cell function. Subsequently, we have for example succeeded in producing near-mature stem cell derived pancreatic islets, that produce insulin in response to elevated glucose. During the second term, we will focus on illuminating how metabolism controls differentiation of stem cells in a tissue environment, and whether metabolic tools can be used to enhance the maturation of lab-grown pancreatic islets for stem cell based diabetes therapy.
  • Jeanssons Stiftelser
    1 January 2022 - 31 December 2023
  • Cancer Foundation Finland
    23 November 2021
  • Academy of Finland
    3 May 2021 - 31 August 2026
    The increasing number of elderly affected by age-related blood dysfunction and malignancies is one of the most significant public health challenges today. A major contributor to this age-related decay is the loss of blood stem cell function. Nevertheless, we know little of how blood stem cells become dysfunctional with age. Our previous work demonstrates that blood cell size is a key determinant of stem cell function and that enlargement of blood stem cells contributes to their fitness decline during aging. This project is anticipated to reveal how blood stem cells lose their fitness upon enlargement during aging and whether this increase in their size facilitates cancerous transformation. It is essential to further our understanding of the role of stem cells in aging and cancer to offer new therapeutic implications for rejuvenation therapies that improve stem cells function and thereby preserve the health of an aging or cancerous blood system.
  • Cancer Foundation Finland
    10 November 2020
  • Implications of changes in cellular size on cell division and aging
    Jane Coffin Childs Memorial Fund for Medical Research
    1 July 2018 - 30 June 2021
  • Swiss National Science Foundation
    1 January 2017 - 30 June 2018
  • Swiss National Science Foundation
    1 December 2013 - 30 November 2016
  • Swiss National Science Foundation
    1 January 2010 - 30 June 2013

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