Mechanisms of Wnt signaling in stem cells, development and cancer

The overall aim of our work is to gain a fundamental understanding of the dual nature of WNT signals that guide homeostatic tissue renewal and cancer cell growth. Deregulated WNT signaling due to mutations is strongly linked to cancer. 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 for cancer growth. Research interests: 

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. 

Elucidate the impact of cancer mutations 
We discovered that cancer mutations can endow tumor suppressors with novel functional properties that promote cancer growth and progression. We aim to obtain a mechanistic understanding of how such mutations alter the structure and activity of tumor suppressors to provide novel clues on how to interfere with signaling aberrations in cancer. 

Modulate WNT signaling 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, and generate nanoparticles to detect and isolate stem cell populations from complex tissues.

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 tumor progression and to the development of novel anti-cancer strategies.

Group members