Research Description

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

The Wnt and Hedgehog families of secreted proteins play fundamental roles during embryonic development but also in adult animals for tissue homeostasis. When these proteins bind to the surface of target cells it affects their proliferation, differentiation and migration.

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.

As detailed below, the main focus of my lab is to leverage powerful novel proteomic and genomic technologies to continue examining 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.

Identify the molecular mechanisms of Wnt and Hedgehog signalling.

Our laboratory has a long-standing interest in deciphering the molecular mechanisms deciphering Wnt and Hedgehog signal transduction. Over the years, we have optimized mass-spectrometry approaches for the identification of new proteins implicated in these signalling pathways. We are also interested in studying the post-translational modifications (e.g. phosphorylation, ubiquitination) of theses proteins and how they affect signalling. More recently  in a collaboration with Dr. Jason Moffat at the University of Toronto, we have developed Cas9/sgRNA libraries that we are using in genome-wide screens to identify genes modulating Wnt and Hedgehog signals in normal and cancer cells.

Development of new therapeutics targeting the Wnt and Hedgehog 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.

Positions available in the Angers lab.

June 2017

Postdoc positions in Cancer biology, Angers lab at the University of Toronto.

Two Post-Doctoral positions are available immediately in the laboratory of Stephane Angers in the Leslie Dan Faculty of Pharmacy (www.angerslab.org), University of Toronto, to develop strategies to inhibit developmental signalling pathways in cancer.

Our laboratory is studying the genetic circuitry important for cancer development to identify vulnerabilities that could be harnessed for the development of new medicine. Our approach involves genome-wide CRISPR functional screens, which we perform in cancer cell lines and primary cells to identify context-dependent fitness genes important for cancer cell growth. Our recent work identified the Wnt receptor Frizzled-5 as being essential for the growth of a subset of pancreatic cancers (Steinhart et al, Nature Medicine 2017). In collaboration with the group of Dr. Sachdev Sidhu we are developing synthetic antibodies targeting Wnt components and other cell surface proteins involved in cancer progression.

We are looking for a highly motivated, self-directed postdoctoral fellow with strong team capabilities. Preference will be given to candidate that recently obtained their Ph.D (less than 12 months) and that have a keen interest to develop and independent research program in the areas of genomics, cell signaling and cancer biology. The ideal candidate will have a strong publication record as a first author in the field of cancer biology with expertise in either organoid models, mouse models, cell signaling or antibody development.

Please submit your application as a single PDF document to stephane.angers@angerslab.org with the following information: a cover letter, statement of interest, and CV with contact details for 3 referees.

Publications

View all publications on PubMed