For best experience please turn on javascript and use a modern browser!
uva.nl

dr. M.F.M. (Marco) Hoekman

Faculty of Science
Swammerdam Institute for Life Sciences

Visiting address
  • Science Park 904
  • Room number: C2.204
Postal address
  • Postbus 94246
    1090 GE Amsterdam
  • Research Lines Hoekman Lab

    Research in our lab is centered around the molecular mechanisms underlying cortical development and circadian rhythms. Specifically, we are interested in how transcriptional programs are involved in the formation of cortical structures and the regulation of ciradian rhythmicity.

     

    Our interest in how transcriptional programs shape the developing and adult brain started when screening for transcription factors expressed in the adult mouse hippocampus. As a direct consequence, a novel member of the mammalian FoxO family, FoxO6, was discovered (Jacobs et al. 2003, J Biol Chem). Apart from analyzing the expression profile in the embryonic and adult brain, we performed several functional studies, one of which showed that FoxO6, in contrast to the other FoxOs, is not able to translocate from the nucleus to the cytoplasm. Normally, FoxOs are responsive to insulin and insulin-like growth factors, rendering them inactive via PKB-dependent translocation to the cytoplasm. Although FoxO6 lost its ability to modulate its transcriptional activity via translocation, it is still capable of regulating downstream targets.

     

    Currently, we are working on how FoxO transcrption factors are involved in cortex development. All four mammalian FoxO family members are expressed in the embryonic cortex in an overlapping and complementary manner. Next to using transgenic mouse models we have the in utero electroporation technique running in the lab, enabling us to alter expression of the studied genes in the vivo cortex. Recently, we published a study showing how FoxO6 is involved in neuronal migration by regulation of Plxna4, a known molecular component of the Semaphorin signaling pathway. (Paap et al. 2016, PNAS). 

     

    The second line of research involves the regulation of circadian rhythms via insulin-dependent and FoxO3-mediated signaling.  In collaboration with Dr. I. Chaves and Prof. G.van der Horst (Molecular Chronobiology, Erasmus MC) we have shown that FoxO3 is crucial for circadian rhythms amplitude through direct transcriptional regulation of Clock, one of the core-clock components. Moreover, we were able to modulate circadian rhythm amplitude by the use of insulin (Chaves et al. 2014, Current Biology). At the moment studies are underway to unravel the role of circadian rhythms in both the developing and adult brain.

     

    Key Publications

     

    FoxO6 affects PlxnA4-mediated neuronal migration during mouse cortical development.

    Paap RH, Oosterbroek S, Wagemans CM, von Oerthel L, Schellevis RD, Vastenhouw-van der Linden AJ, Groot Koerkamp MJ, Hoekman MFM and Smidt MP. PNAS 2016  Shared Last author and co-corresponding.

     

    Insulin-FoxO3 signaling modulates circadian rhythms via regulation of clock transcription. 

    Chaves I, van der Horst GT, Schellevis RD, Nijman RM, Koerkamp MG, Holstege MC, Smidt MP and Hoekman MFM. Current Biology 2014  Last author and corresponding.

     

    Spatial and temporal expression of FoxO transcription factors in the developing and adult murine brain. 

    Hoekman MFM, Jacobs FM, Smidt MP and Burbach JP. Gene Expr Patterns 2006

     

    The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation.

    van der Heide LP, Hoekman MFM and Smidt MP. Biochem J 2004

     

    FoxO6, a novel member of the FoxO class of transcription factors with distinct shuttling dynamics.

    Jacobs FM, van der Heide LP, Wijchers PJ, Burbach JP, Hoekman MFM and Smidt MP. J Biol Chem 2003

  • Publications

    2019

    2017

    2016

    • Paap, R. H., Oosterbroek, S., Wagemans, C. M. R. J., von Oerthel, L., Schellevis, R. D., Vastenhouw-van der Linden, A. J. A., ... Smidt, M. P. (2016). FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development. Proceedings of the National Academy of Sciences of the United States of America, 113(45), E7087-E7096. https://doi.org/10.1073/pnas.1609111113 [details]

    2015

    • van der Heide, L. P., Wijchers, P. J. E. C., von Oerthel, L., Burbach, J. P. H., Hoekman, M. F. M., & Smidt, M. P. (2015). FoxK2 is required for cellular proliferation and survival. Journal of Cellular Physiology, 230(5), 1013-1023. https://doi.org/10.1002/jcp.24828 [details]

    2014

    • Chaves, I., van der Horst, G. T. J., Schellevis, R., Nijman, R. M., Groot Koerkamp, M., Holstege, F. C. P., ... Hoekman, M. F. M. (2014). Insulin-FOXO3 signaling modulates circadian rhythms via regulation of clock transcription. Current Biology, 24(11), 1248-1255. https://doi.org/10.1016/j.cub.2014.04.018 [details]

    2012

    2017

    This list of publications is extracted from the UvA-Current Research Information System. Questions? Ask the library or the Pure staff of your faculty / institute. Log in to Pure to edit your publications. Log in to Personal Page Publication Selection tool to manage the visibility of your publications on this list.
  • Ancillary activities
    • No ancillary activities