Christopher Overall: "Deciphering roles for proteases in regulating immunity and cancer through proteomics and mouse models"

Christopher Overall
Center for Blood Research, University of British Columbia, Canada

Deciphering roles for proteases in regulating immunity and cancer through proteomics and mouse models

Proteomics technologies are revolutionizing the way in which drug targets can be identified, validated and assessed. To understand the role of proteases in inflammation and metastasis we developed new quantitative proteomics approaches (Nature Biotechnology 28, 281-288, 2010, Nature Methods 7, 508-511) to identify cleaved substrates on a global scale. Using activity based F18 probes active MMP proteases can also be imaged in cancer. By these approaches we identified proteolytic signatures in disease, and numerous novel protease substrates and uncovered incredible complexity in the protease web. The unmasking of cytokines, such as VEGF, by metalloproteinase processing of their binding proteins is a new mechanism in the control of cytokine activation and angiogenesis. This underscores the potential of specialized proteomics techniques to tackle role of proteases in regulating complex proteomes.