Research Groups

Baron group

Our research focuses on myelin biogenesis in health and disease (particularly multiple sclerosis, MS) on topics related to trafficking and signalling in oligodendrocytes. We have identified the polarized nature of oligodendrocytes, in which cognate apical-like and basolateral-like trafficking routes exist for the transport of protein and lipids to the cell body plasma membrane and myelin membrane, respectively. Another aspect of our work aims at revealing the role of neuronal factors and the relevance of various extracellular matrix constituents present in MS lesions that modulate oligodendrocyte differentiation and myelination. We have identified environmental signalling abnormalities in MS lesions, such as fibronectin aggregates and the persistent presence of neuronal galectin-4, that hamper oligodendrocyte maturation. Currently, we aim to devise strategies that reverse signal malfunctioning of fibronectin aggregates and galectin-4 so as to favor the development of therapeutics to promote endogenous remyelination and/or overcome remyelination failure in MS lesions, thereby halting disease progression. Recently we started to study remyelination efficiency from a heterogeneity point of view considering both regional differences between glial cells present in the grey and white matter as well as differences between glial cells of people with and without MS.

  • People
  • Publications
  • Grants
  • Dissertations
  • Students
  • Alumni
  • Links
  • Wia Baron PhD Visit
    Position

    Principal Investigator

    Research fields

    Myelin biogenesis, multiple sclerosis (MS), trafficking and signalling in oligodendrocytes, ECM

    PhD students
    Jody de Jong MSc
    Visit
    Wendy Oost MSc
    Visit
    Marion Wijering MSc
    Support
    Sharon Brouwer B.A.Sc
    Naomi Dijksman MSc
      • Selected Publications:
      1. Werkman, I.L., Dubbelaar, M.L., van der Vlies, P., de Boer-Bergsma, J.J., Eggen B.J.L., and Baron, W. (2020). Transcriptional heterogeneity between primary adult grey and white matter astrocytes underlies differences in modulation of in vitro myelination. J. Neuroinflammation. 17:373.
      2. Werkman, I., Sikkema, A.H., Versluijs, J.B., Qin, J., de Boer, P., and Baron, W. (2020). TLR3 agonists induce fibronectin aggregation by activated astrocytes: a role of pro-inflammatory cytokines and fibronectin splice variants.  Rep. 10:532
      3. de Jong, C.G.H.M., Stancic, M., Pinxterhuis, T.H., van Horssen, J., van Dam, A.-M., Gabius, H.-J., and Baron, W. (2018). Galectin-4, a negative regulator of oligodendrocyte differentiation is persistently present in axons and microglia/macrophages in multiple sclerosis lesions.  Neuropathol. Exp. Neurol. 77:1024-1038.
      4. Wang, P., Gorter, R.P., de Jonge, J.C., Nazmuddin, M., Zhao, C., Amor, S., Hoekstra, D., and Baron, W. (2018), MMP7 cleaves remyelination-impairing fibronectin aggregates and its expression is reduced in chronic multiple sclerosis lesions, Glia 66:1625-1643.
      5. Lentferink, D.H., Jongsma, J.M., Werkman, I., and Baron, W. (2018), Grey matter OPCs are less mature and less sensitive to IFNg than white matter OPCs: consequences for remyelination, Sci Reps. 8:2113.
      6. Stoffels, J.M.J., Hoekstra, D., Franklin, R.J.M., Baron, W., and Zhao, C. (2015), The EIIIA domain from astrocyte-derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination. Glia 63, 242-256.
      7. Stoffels, J.M., de Jonge, J.C., Stancic, M., Nomden, A., van Strien, M.E., Ma, D., Sisková, Z., Maier, O., ffrench-Constant, C., Franklin, R.J., Hoekstra, D., Zhao, C., and Baron, W.(2013), Fibronectin aggregation in multiple sclerosis lesions impairs remyelination. Brain 136, 116-131.
      8. Stancic, M., Slijepcevic, D, Nomden, A., Vos, M.J., de Jonge, J.C., Sikkema, A.H., Gabius, H.J., Hoekstra, D., and Baron, W. (2012), Galectin-4, a novel neuronal regulator of myelination., Glia60, 919-935.
      9. Baron, W., Decker, L., Colognato, H., and ffrench-Constant, C. (2003), Regulation of integrin growth factor interactions in oligodendrocytes by lipid raft microdomains. Curr. Biol. 13, 151-155.
      10. Baron, W., Shattil, S.J., and ffrench-Constant, C. (2002), The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of avb3 integrins. EMBO J. 21, 1957-1966.
  • Ongoing projects/grants (selection):

    2020-2021: Out-of-the-box grant, Moves and Stichting MS Research (with Sander van Kasteren): EBV-infected B cells as essential inducers of demyelination in multiple sclerosis.

    2018-2023: Program Grant Stichting MS Research (with MSCNN) : An integrative analysis of MS lesions to prepare the scene for effective remyelination therapy

    2017-2021: Project grant Stichting MS Research (with Inge Zuhorn): Delivery of a novel therapeutic drug to the brain for myelin repair in multiple sclerosis

    2017-2022: National Lotery ‘ VriendenLoterij grant, Stichting MS Research (with MSCNN): Establishment of an MS patient-derived iPS cell bank: towards a human MS lesion model in a dish

  • Dissertation supervised by W. Baron (co-promotor):

    2021

    Lentferink, D.H. (2021). Regional diversity in oligodendrocyte progenitor cells: implications for remyelination in grey and white matter. [Groningen]: University of Groningen

     2020

    Werkman, I. (2020). Macroglia diversity and its effect on myelination [Groningen]: University of Groningen

    Espitia Pinzon, N. (2020). Role of tissue Transglutaminase in glial cell processes involved in multiple sclerosis [Amsterdam]: Vrije Universiteit Amsterdam

    2018

    Wang, P. (2018). On the role of macrophages, microglia and the extracellular matrix in remyelination [Groningen]: University of Groningen

    2018

    Wang, P. (2018). On the role of macrophages, microglia and the extracellular matrix in remyelination [Groningen]: University of Groningen

    2016

    Bijlard, M. (2016). On the cause of multiple sclerosis: Molecular mechanisms regulating myelin biogenesis [Groningen]: Rijksuniversiteit Groningen

    2014

    Stoffels, J. (2014). Multiple sclerosis, remyelination and the role of fibronectin [Groningen]: University of Groningen

    Ozgen, H. (2014). Myelin biogenesis: Dynamics of MBP, PLP and galactolipids [Groningen]: University of Groningen

    2012 

    Mirjana Stancic (2012). Galectins, (re)myelination and multiple sclerosis pathology [Groningen]: University of Groningen

    2007

    Bert Klunder (2007). Sorting and trafficking of proteins in oligodendrocytes during myelin membrane biogenesis) [Groningen]: University of Groningen

    2006

    Zuzane Siskova (2006): Extracellular matrix and (re)myelination. [Groningen]: University of Groningen

  • Student projects:

    Students (bachelor, masters or technician school) who are interested to perform an internship in our group are welcome to apply. We have ample opportunities, and I would be happy to explain our research goals and possibilities for research projects in more detail. Minimal length is 3 months.

    You can apply via this application form.

  • PhD students:
    Zuzana Šišková (2006)
    Bert Klunder (2007)
    Mirjana Stancic (2012)
    Josephine Stoffels (2014)
    Hande Ozgen (2014)
    Marjolein Bijlard (2016)
    Peng Wang (2018)
    Inge Werkman (2020)
    Dennis Lentferink (2021)

    Post-docs:
    Olaf Maier
    Tiemen van der Heide
    Michel Vos
    Erik Sikkema

    Technicians:
    Anita Nomden
    Bojana Mikus

  • MS Center Noord Nederland (MSCNN)

     

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