The Wisnovsky Lab: Functional Glyco-Genomics
All living cells are coated with a dense layer of carbohydrate molecules called glycans. The Wisnovsky lab uses cutting-edge functional genomic screening tools to better define the molecular function of these glycans and identify new therapeutic targets for the treatment of disease. Our current specific research interests are described below.
The Cancer Glyco-Genomic Code
Cancer cells radically alter their cell surface glycans during tumour development. Cancer-associated glycan structures often act as signals that shut off immune activity, helping cancer cells hide from the immune system. The Wisnovsky lab is using CRISPR knockout (CRISPR KO) and CRISPR interference (CRISPRi) screening techniques to identify the molecular pathways in cancer cells that drive these fundamental changes in cellular glycosylation. We expect our work to identify new cancer-specific vulnerabilities that can be targeted for tumour immunotherapy.
Defining New Ligands for Orphan Glycan-Binding Receptors
Human immune cells express hundreds of glycan-binding receptors that transmit specific intracellular signals upon binding to specific glycosylated ligands. The Wisnovsky lab uses high-throughput CRISPR activation (CRISPRa) screening, along with an array of targeted biochemical techniques, to define the complex glycoprotein structures that bind to receptors of interest. Understanding these ligand-receptor interactions can help us build new tools and strategies for therapeutically modulating the immune system.
New Technologies for Glycome-Wide Screening
Hundreds of distinct glycan structures are attached to thousands of different protein scaffolds on the cell surface. The Wisnovsky lab is building new CRISPR-based technologies that will allow us to directly screen the function of these glycans in a pooled, high-throughput manner. We hope these tools will create new opportunities in translational glycoscience.
