Dr. James Dennis

Lunenfeld-Tanenbaum
Research Institute
Mount Sinai Hospital
Joseph & Wolf Lebovic Health Complex
600 University Avenue
Toronto Ontario M5G 1X5

Tel: 416-586-4800 ext.8233
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Dr. Jim Dennis

SENIOR INVESTIGATOR

Dr. Jim Dennis draws on a broad range of expertise, including structural biology, biochemistry, genetics and cell biology in his investigation of the cellular mechanisms involved in cancer, diabetes, autoimmune disease. These diseases often occur in midlife, and represent a large loss in productive years and increase in health cost to Canadians.

Our knowledge of the genetic factors underlying these conditions is growing rapidly with recent advances in technology for genome sequencing, proteomics and systems biology. There is a renewed appreciation that basic metabolism works intimately with genes to determine normal and disease process. 

In a groundbreaking study published in the prestigious journal Cell in 2007, Dr. Dennis reported a new role for sugar metabolism in the modification of proteins on the cell surface. These findings provide an important mechanism of adaptation at the cell surface, thus responsiveness to cues outside the cell as conditions change. More recently the lab is exploring the evolution of this adaptive system to better understand genetic risk factors in humans. Dr. Dennis' group has also developed computational models to help predict disease severity for newly discovered gene variants.

At a Glance

• Studies on loss of growth control in cancer cells
• Metabolism, signaling and molecular adaption at the cell surface
• Dr. Dennis is a Fellow of the Royal Society of Canada
• Canada Research Chair in Glycobiology
• Lloyd S.D. Fogler (QC) Award of Excellence in 2011
• Co-founder of GlycoDesign Inc. in 1998 and Glixis Inc. in 2012.
• Current focus is gene-metabolism interactions in cancer and autoimmune disease.

Major Research Activities

Dr. Dennis laboratory is studying the role of
Asn (N)-glycosylation in cytokine receptors, glucagon receptor and solute transporters, their trafficking and signaling in cell culture systems relevant to cancer, diabetes and autoimmunity. He has made seminal contribution on the role of protein N-glycosylation and signaling in development and disease using mice,
C. elegans and human experimental models. He pioneered a unifying computational model of growth factor receptor regulation based on metabolic input to Golgi-dependent modification of their N-glycans. The model has been used to search for and explain heritable genetic and metabolic susceptibility to autoimmune disease, and lead to novel paradigms for diagnostic and treatment. Current works is focused on gene-metabolism interactions in cancer and autoimmune disease using CRISPR/Cas9 gene editing metabolite analysis by mass spectrometry.

Dr. Carol Swallow is a clinician-scientist working with
Dr. Dennis in his lab on tumor suppressor genes that promote genome instability, a frequent event leading to cancer progression and spread. One copy of the Polo family kinase Plk4/Sak is often lost in human liver cancers, and in mice this event strongly promotes genome instability and liver cancer. Drs. Dennis and Swallow are using screening for Plk4 interacting proteins required for mitosis, cell division and cancer metastasis.

Recent Publications