Grant: Foundation Grant

Chronic inflammatory diseases like periodontitis, arthritis and lupus affect 82% of Canadians and for the 1/2000 Canadians with immunodeficiencies, untreatable infections are imminent threats as drug resistance rises. These diseases commonly involve loss of disease-fighting defense proteins. I discovered that defense proteins are lost after they are cut by white blood cell immune proteases. In immunodeficiencies, inherited genetic defects reduce defense proteins in white blood cells. These crucial discoveries were possible by my innovative and highly advanced techniques known as degradomics. Degradomics is a method of uniquely identifying the cut ends of proteins by selectively purifying them from the rest of the protein. As cuts are formed only during active disease, these segments are highly valuable as disease markers to develop new clinical tests. By detecting and treating earlier, inflammatory diseases are easier to manage before disease worsens, and thus reduce long-term disability. Also, as part of the international Human Proteome Project consortium, I am using degradomics to identify the natural ends of all human proteins. This will allow us to characterize the functions of normal vs. diseased proteins and hence reveal new disease mechanisms. I will now use degradomics to generate clinically relevant knowledge on how proteases damage disease-fighting defense systems in human inflammatory and immunodeficiency diseases. I will obtain human tissues discarded in treatment, e.g. inflamed gum from wisdom teeth extractions, and study white blood cells from patients. As defense proteins are alike in many diseases, my results will be broadly applicable. This knowledge will translate to develop new drugs to combat inflammatory and autoimmune diseases. From identifying cut protein ends in these diseases, I will reveal the damaging proteases that can be targeted with new drugs to improve health of Canadians and thereby ensuring sustainable health care costs.