Mariann_Bienz

Mariann Bienz

Molecular mechanisms of Wnt signal transduction
mb2@mrc-lmb.cam.ac.uk

The Wnt signalling pathway controls animal development and tissue homeostasis, and is also a major cancer pathway. Its key effector is β-catenin, which is stabilized in response to Wnt stimulation; it thus binds to TCF factors in the nucleus, and functions as a co-activator to mediate Wnt-induced transcription. Inappropriate activation of β-catenin can cause cancer in many human tissues, most notably colorectal cancer.

We study the functions of individual Wnt signalling components and their molecular interactions, using cell-biological, biochemical and structural approaches, as well as fly and mouse animal models. One focus is on the role of Dishevelled, a dynamic polymeric adaptor that transduces the Wnt signal from the plasma membrane to the Axin complex, which also contains the Adenomatous polyposis coli (APC) tumour suppressor and inactivates β-catenin.

Our other focus is on the mechanism of β-catenin-mediated transcription, and how this process may be controlled by the histone-decoding Pygo-BCL9 complex, and by ubiquitin turnover mediated by APC-associated Trabid.

We aim to develop the potential of these Wnt signalling components as drug targets and, ultimately, to discover small molecules that inhibit their interactions and signalling activities.

Selected Papers

Group Members

  • Julius Mieszczanek
  • Marc Fiedler
  • Ashraf Ibrahim
  • Benjamin Moore
  • Nikola Novcic
  • Moore van Tienen
  • Melissa Gammons
  • Miha Renko