The long-term research goal of my laboratory is to understand the cellular and molecular basis of cadherin-mediated adhesion in normal cell growth, development and tumourigenesis. In human cancer, it is tumour metastases to vital organs such as the lungs and liver, and not the primary tumour itself that proves fatal. However, despite significant advances in our understanding of the underlying principles of tumour initiation, the mechanisms governing tumour progression from the benign to the malignant invasive phase remain poorly understood. Hence a thorough understanding of the factors that regulate and control cell adhesion and motility would significantly facilitate the development of improved cancer therapies.

To this end we specifically focus on the primary epithelial cell-cell adhesion system involving E-cadherin and its catenin cofactors α-, β-, γ- and p120 catenin, which is perturbed in ~50% of human metastatic tumours and contributes to the invasive phenotype. Interestingly, the Armadillo catenins β-, γ- and p120 catenin also function as transcriptional regulators of genes involved in tumourigenesis. This alternative mechanism for contributing to tumour malignancy is best exemplified by β-catenin, which interacts with the Lef/TCF family of transcription factors to constitutively activate genes implicated in tumourigenesis (e.g. c-myc, cyclinD1, ID2, matrilysin).

My laboratory focuses on the transcription factor Kaiso that was first identified as a specific binding partner for p120 catenin, which is aberrantly expressed or absent in human breast, colon and skin carcinomas . Kaiso is a novel member of the POZ-zinc finger family of transcription factors implicated as oncoproteins or tumor suppressors, and currently it is the only known POZ protein with dual-specificity DNA-binding and transcriptional repression activity; Kaiso recognizes a sequence-specific consensus, TCCTGCNA, or methylated CpG-dinucleotides.