Our overall aim is to identify molecular mechanisms that control cellular plasticity and suppress tumour growth. We study epithelial cells in particular as they give rise to ~80% of cancers. Epithelial cells have the unique property of cell polarity, which acts as a first line of defence against infection and a barrier against cancer cell invasion. We investigate how external signals, such as infection, may influence cell polarity, cellular plasticity and cell fate determination. Several of our projects focus on the ASPP proteins (Apoptosis-Stimulating Protein of p53; Ankyrin repeats, SH3 domain and Prolin rich sequence containing proteins), which regulate cell polarity/adhesion and the transcriptional activity of p53 family members.
Stemming from our work on ASPPs, which uncovered a new mechanism of nuclear entry, we recently proposed the definition of a distinct class of signalling effectors that respond to external signals by translocating from the cytoplasm to the nucleus where they regulate transcription without binding DNA directly (which we term STRaNDs for Shuttling Transcription Regulators that are Non-DNA binding). Many STRaNDs, including the ASPPs, beta-catenin and YAP, are guardians of cellular plasticity.
We are working closely with clinicians to investigate cell plasticity in upper gastrointestinal tract cancer initiation and resistance to therapy (oesophageal cancer and gastric cancer).
Current research topics include:
- Understanding selective transcription in cell fate determination
- Identifying regulators of cellular plasticity in upper gastrointestinal cancer initiation and metastasis
- Understanding the influence on cellular plasticity of Helicobacter pylori and Epstein Barr Virus (EBV) infection