Stephane Angers

Stephane Angers

Professor

BSc, McGill University, 1997
PhD, Université de Montréal, 2002
Postdoc, University of Washington, HHMI, 2002-2006

Address Leslie Dan Faculty of Pharmacy
144 College Street, Room 901
Toronto, ON
Toronto, ON M5S 3M2
Lab Angers Lab
Lab Phone 416-946-0135
Office Phone 416-978-4939
Email stephane.angers@utoronto.ca

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.

 

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Research Lab

The Angers lab studies the molecular mechanisms underlying the inter and intracellular signal transduction events controlled by the Wnt and Hedgehog families of secreted Growth Factors. We use an integrative approach combining proteomic and genomic tools to identify novel components in these signalling pathways and study their normal functions during development and tissue homeostasis in adults but also how these molecules become dysregulated in human diseases such as cancer.

Learn more: Angers Lab

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.

canonical-wnt

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.

 

Awards & Distinctions

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

Courses Taught

BCH 2110H Eukaryotic Signaling
BCH 2024H Advances in Precision Medicine
BCH473Y Advanced Research Project in Biochemistry

Extra-Departmental Courses

PHC301/PHM323 Molecular mechanisms of drug action
PHC300/PHM140 Molecular Pharmacology

Publications

View all publications on PubMed