Areas of expertise
Madelon Maurice studied Medical Biology at the Free University, Amsterdam and earned her PhD in 1998 at the Department of Rheumatology, LUMC, Leiden, The Netherlands. Through postdoctoral training in the leading laboratories of Hidde Ploegh, Harvard Medical School, Boston, USA, and Hans Clevers, Hubrecht Institute, Utrecht, she gained expertise in a diverse set of disciplines (biochemistry, cell biology, cancer biology, mouse genetics). She now uses this multidisciplinary expertise to address key questions in the fields of stem and cancer cell biology. She was appointed assistant professor at the department of Cell Biology, UMC Utrecht in 2006 and was promoted to associate professor in 2012. Her primary research interests concern the molecular mechanisms by which WNT signals guide stem cell maintenance and tumour cell growth. The innovative nature of her work was awarded by an ERC Starting Grant (2009) and a prestigious VICI grant from the Dutch Research Council (2014). She is the coordinator of the Marie Curie Sklowdowska EU ITN consortium “WntsApp”, comprising 7 academic and 3 private sector European partners (wntsapp.eu) that aim to uncover the molecular basis of WNT receptor signal relay and develop novel peptide-based therapeutics to interfere with Wnt receptor activity.
Women in science
'Women in science' was initiated by the University of Utrecht.
Research program / group
The overall aim of our work is to gain a fundamental understanding of the dual nature of signals that guide homeostatic tissue renewal and cancer cell growth. WNT proteins comprise a large family of conserved, secreted glycolipoproteins that control the maintenance and proliferation of stem cell reservoirs that mediate tissue self-renewal and regeneration after injury. Deregulated WNT signaling due to mutations is strongly linked to cancer and degenerative disease. Mechanistic insight in how cells control their responses to WNT is key to understand how pathway sensitivity and specificity is controlled in normal stem cells and how these events are exploited in cancer.
1.) Understanding WNT receptor-mediated signal relay
WNT binding to cell surface receptors is decisive for downstream gene activation but the regulatory mechanisms that operate at the receptor level remain poorly understood. We aim to uncover how cells interpret WNT signals received at their cell surface and how dysregulation of receptor-mediated signal relay by mutations leads to cancer.
2.) Elucidate the impact of cancer mutations
We discovered that cancer mutations can endow tumour suppressors with novel and unique activities to drive cancer growth and progression. We aim to obtain a mechanistic understanding of how these mutations alter the structure and activity of tumour suppressors to provide novel clues on how to interfere with signalling aberrations in cancer.
3.) Modulate WNT signalling in stem and cancer cells
Our fundamental research is integrated with ongoing efforts to translate our findings into applications. We are developing therapeutically relevant peptide-based reagents that modify WNT receptor activity (www.wntsapp.eu), and generate nanoparticles to detect and isolate stem cell populations from complex tissues (http://bit.ly/1ZgcCyP).
We use an integrated multidisciplinary approach including methods at the atomic level (fluorescence spectroscopy, peptide libraries), at the molecular level in cells (biochemistry, microscopy, gene silencing, proteomics) and in the living animal (organoids, animal models). With these approaches we aim to contribute to novel paradigms on signaling and mutation-induced tumour progression and to the development of novel anti-cancer strategies.
- Madelon Maurice - PI
- Eline van Kappel - PhD student
- Nicola Fenderico - PhD student
- Manja Omerzu - PhD student
- Tomica Kralj - PhD student
- Huiying Ma - PhD student, shared with Pathology
- Ingrid Jordens - postdoc
- Alba Cristobal Gonzalez - postdoc
- Despina Xanthakis - technician
- Peter van Kerkhof - lab manager
- Gerlach JP, Emmink B, Nojima, H, Kranenburg O, Maurice MM (2014) Wnt signalling induces accumulation of phosphorylated β-catenin in two distinct cytosolic complexes, Open Biology Nov;4(11):140120
- Consonni SV, Maurice MM, Bos JL (2014) DEP domains: structurally similar but functionally different, Nature Rev Mol Cell Biol, 15: 357–362.
- Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJR, Maurice MM* and Clevers H* (2012) Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors. Nature,488:665-669 (*corresponding)
- Tauriello DVF, Jordens I, Kirchner K, Slootstra J, Kruitwagen T, Bouwman, BAM, Rudiger SGD, Schwamborn K, Schambony A, Maurice MM (2012). Dvl employs its DEP domain and C-terminus to bind a discontinuous motif in the Fz receptor and initiate Wnt/β-catenin signalling. Proc Natl Acad Sci U S A. 109(14):E812-20
- Tauriello DVF, Haegebarth A, Kuper I, Canninga-van Dijk M, Edelmann MJ, Henraat M, Kessler, BM, Clevers H, Maurice MM (2010) Loss of the tumor suppressor CYLD enhances Wnt/β-catenin signaling through K63-linked ubiquitination of Dvl. Mol Cell 37: 607-619
More contact information
Department of Cell Biology, G02.525
Wieke van der Kuijl en Betty Hartgring
+31 (0)88 75 56551