Research

Molecular mechanisms underlying intracellular signalling activated by the Wnt and Hedgehog families of secreted growth factors.

Since they are implicated in fundamental cellular processes, mutations or aberrant regulation of the proteins implicated in the intracellular signalling events controlled by Wnt and Hedgehog ligands are often found in human diseases such as Cancer.

Research in the last 30 years has identified several of the core components
of these important signalling pathways and has helped explained their deregulation in diseases. Many questions however remain.

The main focus of the Angers lab is to leverage powerful novel proteomic and genomic technologies to examine how the Wnt and Hedgehog pathways function in normal and human disease contexts. We are also interested in leveraging this knowledge to identify new therapies based on modulating these pathways.

 

 

Development of new therapeutics targeting developmental pathways.

Wnt and Hedgehog are well described to control the self-renewal and/or proliferation of stem and progenitor cell populations. Since the same mechanisms are likely involved in directing cancer stem cells, intense efforts are deployed by several groups to determine if these pathways are good targets and to identify which components are to be targeted in diverse contexts. Indeed, a requirement for Wnt ligands emanating from the tumour niche is thought to be needed for the progression of most human tumours (except perhaps for colon cancer, where Wnt-bcatenin signalling is activated due to downstream mutations in APC). In collaboration with Sachdev Sidhu at the University of Toronto, we are developing synthetic antibodies systematically blocking all Wnt receptors and testing their anti-cancer properties.

 

Deciphering the molecular wiring of high fatality cancers using functional genomic screens.

Glioblastoma and pancreatic ductal adenocarcinomas are two cancers with especially poor prognosis. Using genome-wide CRISPR-Cas9 functional screens performed in patient-derived cancer stem cells, we are identifying genes that are essential for the growth of these cancers. We are also performing chemogenomic screens to identify mechanisms of drug resistance and new genes conferring hypersensitivity to standard of care therapeutic drugs.