Elucidating the role of EMT modulators in Acute Leukaemia

Background: The epithelial-mesenchymal transition (EMT) is a key developmental process that plays an important role during epithelial tumour development and pathogenesis. Activation of EMT in tumour cells contributes to the development of the migratory and invasive phenotype required for effective tumour cell metastasis. Furthermore, expression of EMT modulators has also been linked to the acquisition of cancer stem cell properties and enhanced therapeutic resistance in epithelial tumour cells. Intriguingly, we and others have more recently discovered that altered expression of EMT modulators, such as members of the SNAIL and ZEB families, also plays a role in the development and pathogenesis of Acute Leukaemias. The exact mechanisms involved, however, remain to elucidated. Project: In this project, you will use a variety of genetic, genomic and proteomic approaches in cell lines and in vivo leukaemia models to identify the key mechanisms utilised by EMT modulators to drive Leukaemia development and pathogenesis. Large scale drug and genetic screens may also be employed to identify unique EMT-driven therapeutic vulnerabilities in our Leukaemia models, paving the way for development of novel treatment approaches.