Stephane Angers

Dr. Angers is an expert in the field of signal transduction. He obtained his Ph.D from the Université de Montréal in 2002 under the guidance of Dr. Michel Bouvier. His thesis work led to the development and application of light energy transfer methodology for the study of protein-protein interaction and signal transduction. From 2002-2006 he was a Howard Hughes Post-Doctoral Fellow at the University of Washington in Seattle under the supervision of Dr. Randall T. Moon, where he identified and characterized novel components of the Wnt signalling pathway and a new class of E3 ubiquitin ligases.

In October 2006, Dr. Angers established his independent research program in the Department of Pharmaceutical Sciences at the Faculty of Pharmacy and in the Department of Biochemistry at the University of Toronto. He is the recipient of the Canada Research Chair in Functional Architecture of Signal Transduction. His research program is developed to understand the signalling mechanisms underlying the Wnt and Hedgehog families of growth factors and their signalling mechanisms in development, adult tissue homeostasis and in human diseases. His pioneer work led to the development of novel antibody molecules blocking and activating the Wnt pathway for the treatment of cancers and regenerative medicine applications. He is the scientific founder of two biotech companies, ModMab Therapeutics and AntlerA Therapeutics, which are pursuing the clinical development of these molecules.

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.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.

Appointments, Cross Affiliations, Memberships

Director, Donnelly Centre for Cellular and Biomolecular Research
Professor, Pharmaceutical Sciences
Canada Research Chair in Functional Architecture of Signal Transduction

Courses Taught

BCH 2110H Eukaryotic Signaling
BCH 2113H Advances in Precision Medicine
BCH473Y Advanced Research Project in Biochemistry
PHC301/PHM323 Molecular mechanisms of drug action
PHC300/PHM140 Molecular Pharmacology

Awards

2009 — Canadian Society for Pharmaceutical Sciences, GSK Early Career Award
2008 — Ontario Early Researcher Award  
2007 — Canada Research Chair  
2000 — ACFAS Bernard Belleau Award