Canada Research Chair Senior Investigator & Professor Departments of Molecular Genetics and Laboratory Medicine and Pathology Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital Toronto, Ontario
N-glycosylation and metabolism: a critical network in cancer progression
Metabolic reprograming in cancer cells increases the flux of glucose into anabolic pathways including the Hexosamine Biosynthesis Pathway (HBP) which supplies UDP-GlcNAc to N-glycan branching. We have shown that loss-of-function in these pathways suppresses cancer progression, alters T cell regulation and risk of autoimmune disease, and plays a role in glucose homeostasis. The branching and elongation of N-glycan chains found on cell surface receptors generates a gradation of affinities for carbohydrate-binding proteins, the galectin, selectin and siglec families. These interactions adapt cellular responsiveness to environmental conditions. Attesting to their importance, glycoproteins display accelerated evolution rates proportional to N-glycosylation site multiplicity during vertebrate radiation. Complex polygenetic diseases involve multiple pathways, and effective treatments are likely to require a better knowledge of gene interactions (SIs). The advent of CRISPR/Cas9 gene editing makes discovery of gene interactions possible on large scale. However, this is a large challenge that requires the collaboration of many research groups. I will discuss the background on our work with HBP and N-glycan branching pathways, and our progress on genome-wide CRISPR/Cas9 screening in query tumor cell lines with specific mutations targeting HBP and N-glycan branching enzymes.
Wednesday, May 2nd, 2018 10:00 - 11:00 am Botterell Hall, Room B139