James Rini

Dr. James Rini obtained his Ph.D. from the department of Medical Biophysics at the University of Toronto where he determined one of the first x-ray crystal structures of a protein-carbohydrate complex. He then did postdoctoral research with Dr. Ian Wilson at the Research Institute of Scripps Clinic where his work on anti-viral antibodies led to the discovery of new principles of immune recognition. As an independent researcher, Dr. Rini has established an international reputation for his contributions in the areas of protein-carbohydrate interactions, animal lectins and glycosyltransferase structure and mechanism. He has written a number of important reviews in these areas and he is a contributor to the popular textbook Essentials of Glycobiology.

Mammalian Cell Membrane and Secreted Proteins/Glycoproteins

The membrane and secreted proteins/glycoproteins of mammalian cells play critical roles in processes ranging from cell-cell communication and signalling to the recognition of foreign antigens.

Specifically, our research efforts are focused on the study of such proteins in three broad areas, described below.

1) Glycosyltransferases and ER Quality Control

The process by which N-glycans mediate protein folding and quality control in the ER is critically dependent on the ability of UGGT, an ER-resident glucosyltransferase, to recognize and glucosylate misfolded proteins.

In contrast, the ER-resident fucosyltransferases, POFUT1 and POFUT2, which are involved in the trafficking of glycoproteins such as the Notch receptor, recognize and fucosylate properly folded protein domains. Through a study of these fundamentally different systems we seek to determine not only the mechanism of action of these glycosyltransferases, but the roles that they play in mediating cellular proteostasis.

2) Human Coronavirus-Receptor Interactions

In addition to SARS-CoV, SARS-CoV-2 and MERS-CoV, human coronaviruses are responsible for ~30% of the common cold. The coronavirus S-protein mediates host cell attachment and fusion of the viral and host cell membranes and among coronaviruses it recognizes a number of different protein and carbohydrate receptors. By studying the S-protein-receptor interaction from a number of different coronaviruses we aim to determine the basis for both host specificity and S-protein-mediated immune evasion and, as such, to shed light on the evolution of this large family of RNA viruses.

3) Carbohydrate Engineering and Improved Therapeutic Antibodies

The N-glycan at Asn-297 of the human IgG molecule plays an important role in modulating Fc-receptor interactions and as a result the clinical efficacy of therapeutic antibodies. Using a combination of approaches including mammalian cell line engineering and the chemoenzymatic modification of the N-glycan at Asn-297, we are developing novel methods for the generation of improved therapeutic antibodies and antibody-drug conjugates for the treatment of cancer and arthritis.

Appointments, Cross Affiliations, Memberships

Professor Department of Molecular Genetics

Courses Taught

BCH374Y1 Research Project in Biochemistry
JBB2025H Protein Crystallography
BCH473Y Advanced Research Project in Biochemistry
BCH440H (BCH1440H) Protein Homeostasis
BCH444H Protein Trafficking in the Secretory and Endocytic Pathways