Madelon Maurice Group

Madelon Maurice

Oncode Investigator at UMC Utrecht

My Research

Madelon Maurice earned her PhD in 1998 at the Department of Rheumatology, LUMC, Leiden, the Netherlands on T-cell mediated autoimmunity. She performed postdoctoral training in the laboratories of Hidde Ploegh, Harvard Medical School, Boston, USA, and Hans Clevers, Hubrecht Institute, Utrecht, gaining expertise in a diverse set of disciplines. She initiated her independent research group in 2006 at the department of Cell Biology, UMC Utrecht and became Full Professor of Molecular Cell Biology in 2016. Her primary research interests concern the molecular mechanisms by which WNT signals guide stem cell maintenance and tumor cell growth.

Highlights of her research are: 1) Elucidation of the first known receptor-mediated molecular step in WNT signalling (PNAS 2012). The results altered the general view on how the WNT pathway is initiated to steer activation of β-catenin-mediated transcription. 2) Discovery of the stem cell-specific E3 ligase RNF43 as a novel tumour suppressor that downregulates WNT receptors to inhibit tumour growth (Nature 2012). These findings implicate sensitivity of RNF43 mutant tumors to treatment with WNT receptor inhibitors. 3) Identification of a novel mechanism by which cancer missense mutations endow the tumor suppressor Axin with novel tumor-promoting properties via formation of nano-aggregates (Nature Struct Mol Biol 2016).

From 2013-2017, Madelon coordinated the Marie Curie Sklowdowska EU ITN consortium “WntsApp”, that comprised 7 academic and 3 private sector European partners (wntsapp.eu) that aimed to uncover molecular aspects of WNT receptor signal relay and develop novel peptide-based therapeutics to interfere with aberrant WNT signaling in cancer cells.

Awards

  • 2015: NWO VICI grant
  • 2012: ERC PoC grant
  • 2009: ERC Starting grant

Key Publications

  1. Anvarian, Z., Nojima, H., Van Kappel, E. C., Madl, T., Spit, M., Viertler, M., ... & Richter, K. (2016). Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network. Nature Structural and Molecular Biology, 23(4), 324.
  2. Farin, H. F., Jordens, I., Mosa, M. H., Basak, O., Korving, J., Tauriello, D. V., ... & Clevers, H. (2016). Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature, 530(7590), 340.
  3. Koo, B. K., Spit, M., Jordens, I., Low, T. Y., Stange, D. E., van de Wetering, M., ... & Clevers, H. (2012). Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature, 488(7413), 665.
  4. Tauriello, D. V., Haegebarth, A., Kuper, I., Edelmann, M. J., Henraat, M., Canninga-van Dijk, M. R., ... & Maurice, M. M. (2010). Loss of the tumor suppressor CYLD enhances Wnt/β-catenin signaling through K63-linked ubiquitination of Dvl. Molecular cell, 37(5), 607-619.
  5. Tauriello, D. V., Jordens, I., Kirchner, K., Slootstra, J. W., Kruitwagen, T., Bouwman, B. A., ... & Maurice, M. M. (2012). Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled. Proceedings of the National Academy of Sciences, 109(14), E812-E820.
Contact Information
Madelon Maurice Oncode Investigator

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