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Dr. James Dennis
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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.

 

 
Samuel Lunenfeld 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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Lab Website

 
Jul 15, 2009 04:05 PM

     

At a Glance

  • Studies cells and their loss of growth control in cancer
  • Identifies molecular circuitry controlling adaption of the cell surface
  • Dr Dennis’ research has led to an understanding of sugar modification on surface proteins
  • Experimental models in mice now indicate that novel treatments will be developed based on these findings for cancer, diabetes and autoimmune disease.

 

 

Major Research Activities

Dr. Dennis laboratory is studying the role of N-glycosylation in cytokine receptors, glucagon receptor and solute transporters, their trafficking and signaling in cell culture systems relevant to cancer, diabetes and autoimmunity. This includes discovery and validation of new disease associated genetic polymorphisms. Mass spectrometry for metabolites and N-glycopeptide analysis are being developed. Transgenic mice for tissue-specific over-expression of N-glycolyation enzymes are being made as disease models and therapy testing. Genetic analysis in C. elegans worms has recently reveals that LDL receptor homologues are dependent on N-glycosylation for earliest events in worm development. The human LDL receptor is an important regulator metabolic homeostasis with genetic variants also known to N- glycosylation, thus at the cellular level lessons leaned in the worm model should apply to humans disease.


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. Dr. Dennis and Swallow are using screening for Plk4 interacting proteins required for mitosis, cell division and cancer metastasis.

 

 

Recent Publications

 

 

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