Ken Lau (holding certificate) is joined by (left to right) his supervisor Jim Dennis, Harry Schachter, who provided advice and support throughout the project, and Graduate Coordinator, Jim Rini.

Ken Lau (holding certificate) is joined by (left to right) his supervisor Jim Dennis, Harry Schachter, who provided advice and support throughout the project, and Graduate Coordinator, Jim Rini.

Ken Lau won the Beckman-Coulter Prize for the best graduate student paper of 2007, and gave a lecture on May 29th at the International Symposium Celebrating the 100 Anniversary of the Department of Biochemistry at U. of T.

The Lau et al paper published in Cell (2007) 129:123 entitled “Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation” provides new insight on the role of protein N-glycosylation in the adaptation of the cell surface with changes in metabolism.

Their work demonstrates that the number of N-glycans per polypeptide cooperates with physical properties of the Golgi pathway to regulate surface levels of receptors and transporters. Using computational modeling and experimental examples in T cell and epithelial cells, they show that galectins, a family of mammalian lectins binds to N-glycan on membrane glycoproteins. This multivalent interaction enhances surface residency dependent on the number of N-glycans and their GlcNAc-branching. In turn branching increases with the availability of the donor substrate UDP-GlcNAc. UDP-GlcNAc biosynthesis utilizes key metabolites in carbon, nitrogen and energy homeostasis (fructose-6P, glutamine, acetyl-CoA and UTP). Glycoproteins with high numbers of N-glycans (e.g. EGFR, IGFR, FGFR, PDGFR) tend to be bound to galectins, and exhibit early and graded increase in cell surface expression in responses to increasing UDP-GlcNAc concentration, while glycoproteins with few N-glycans (e.g. TbR, CTLA-4, GLUT4) exhibit delayed and switch-like responses. These results suggest a mechanism for metabolic regulation of cellular transition between growth and arrest arising from apparent co-evolution of N-glycan number and biosynthesis. Animal models of reduced N-glycan branching suggest that this network regulates T cell activation and autoimmunity, tumor progression, glucose metabolism, and stem cell maintenance and aging.

Ken completed his PhD in the Dennis lab and is currently doing postdoctoral work in Dr. Lauffenbergers group at Harvard.