Overall Lab secures $5.55M for inflammatory disease research

August 21, 2016

The Canadian Institutes of Health Research (CIHR) has awarded UBC Dentistry professor Christopher Overall, Canada Research Chair in Proteinase Proteomics and Systems Biology, $5.55 million over seven years for a project titled “Empowering Canada as an international leader in proteomic identification of pathological proteolytic signature biomarkers of inflammatory diseases for discovering disease mechanisms, new diagnostics and treatments”.

This is the largest grant given to any British Columbia scientist for this year and one of the top ten in the country.

Dr. Christopher Overall

Dr. Christopher Overall

Under the guise of CIHR’s new Foundation Grant Program, the funding aims to contribute to a sustainable foundation of health research leaders, by providing long-term support of innovative, high-impact programs of research. To do so, all CIHR grants awarded to a successful investigator are consolidated. Thus although Dr. Overall was also successful in being awarded two other five-year CIHR project grants, a condition of the Foundation Grant is that these be returned.

Chronic inflammatory diseases like periodontitis, arthritis and lupus affect 82 percent 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. Overall 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 his 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, Overall is using degradomics to identify the natural ends of all human proteins. This will allow his team to characterize the functions of normal versus diseased proteins and hence reveal new disease mechanisms.

Over the next seven years he will use degradomics to generate clinically relevant knowledge on how proteases damage disease-fighting defense systems in human inflammatory and immunodeficiency diseases. He will obtain human tissues discarded in treatment, e.g. inflamed gum from wisdom teeth extractions, study white blood cells from patients and placenta from premature babies. As defense proteins are alike in many diseases, his 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, Overall and his team will reveal the damaging proteases that can be targeted with new drugs to improve health of Canadians and thereby ensuring sustainable health care costs.

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