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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
Dr. James Dennis
SENIOR INVESTIGATOR, EMERITUS
Dr. James 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 and 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 series of ground-breaking studies published in the prestigious journals Nature (2001), Science (2004), Cell (2007), and Nature Communications (2011), 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. The capacity for adaptation is often disrupted by chronic disease, stress and aging. Dr. Dennis' group has also developed computational models to help predict disease severity for newly discovered gene variants. 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. More recently the lab has explored the evolution of this adaptive system to better understand genetic risk factors in humans. These studies have revealed rapidly evolving genes as candidates for further study in disease, and also evidence for the impact of protein modification on genomes and the topology of the genetic code.
At a Glance
Studies gene-metabolism interactions, protein glycosylation and growth control in cancer cells.
Dr. Dennis is a Fellow of the Royal Society of Canada.
Co-founder of GlycoDesign Inc. in 1998 and Glixis Inc. in 2012.
Major Research Activities
Dr. Dennis laboratory is studying the role of Asn (N)-glycosylation and Golgi processing in cytokine receptors, glucagon receptor and solute transporters, their trafficking and signaling in cell culture systems relevant to cancer, diabetes and autoimmunity. 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 cancer-associated genes notably, Polo family kinase Plk4/Sak that promote genome instability, a frequent event leading to cancer progression and spread.
