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Christopher M. Overall

B.D.S., B.Sc. (Dent.)(Hons.), M.D.S., Ph.D., F.C.A.H.S., F.R.S.C.
Canada Research Chair in Protease Proteomics and Systems Biology
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Website Lab

Rm: Life Sciences Centre 4.401
2350 Health Sciences Mall
Tel: 604-822-2958
Fax: 604-822-7742

Rm: Life Sciences Centre 4.420
2350 Health Sciences Mall
Tel: 604-822-3561
Fax: 604-822-7742

Research Areas:

Proteomics, degradomics, Human Proteome Project, proteases, Zoonotic Viruses, COVID-19, One Health, MMPs, extracellular matrix biology, anti-viral immunity, innate immunity

Teaching Areas:

Proteomics, degradomics, Human Proteome Project, connective tissue biochemistry and molecular biology,

BIOSKETCH November 2, 2022 
Professor Christopher Overall was appointed a Tier 1 Canada Research Chair in Protease Proteomics and Systems Biology (2001) and a Senior Fellow of the Freiburg Institute of Advanced Studies, Albert-Ludwigs Universität Freiburg, Germany (2010–2013), where he is now an Honorary Professor (2014–). He was inducted as a fellow into the Royal Society of Canada, Academy of Science in 2018. He is best known for his development of proteomic methodology for the discovery of protease substrates in vivo, thereby establishing the field of degradomics. He has used these techniques to reveal new biological roles for proteases in immunity and disease, most recently in the COVID-19 pandemic by SARS-CoV-2 proteases, as well as two new molecular correctors to cure MALT1 protease deficiency in a primary immunodeficiency. By generating clinically relevant insights into how proteases dampen disease-fighting defense systems involved in inflammation and immunodeficiency, degradomics has revealed an unexplored layer of complexity in the hierarchy of cell and immune regulation, greatly adding to our understanding of protease function and drug targeting. 
Dr. Overall completed his B.D.S., Honours Science and Master's degrees at the University of Adelaide, South Australia; his Ph.D. in Biochemistry at the University of Toronto, Canada; and was an MRC Centennial Fellow in his postdoctoral work with Dr. Michael Smith, Nobel Laureate, Biotechnology Laboratory, UBC. During his Ph.D. Dr. Overall was awarded the International Association for Dental Research (I.A.D.R.) Edward H. Hatton Award (1987), the C.A.D.R. Student Research Award (1987), the A.A.D.R., William J. Gies Award (1989), and the Canadian Dental Research Foundation Award (1989). After starting his lab in the Faculty of Dentistry at UBC, Dr. Overall was then awarded the 1991 I.A.D.R. Young Investigator Award in recognition of the significant contribution to Dental Research by a Junior Investigator under the age of 35 years. More recently, he was awarded the International Association for Dental Research Distinguished Scientist Award (2013). 
On sabbatical in 1997 – 1998, he was a Senior Scientist at British Biotech Pharmaceuticals, Oxford, UK, and in 2004 and 2008, a Senior Scientist at the Expert Protease Platform, Centre for Proteomic Drug Discovery, Novartis Pharma, Basel, Switzerland and is now a Creative Destruction Lab Scientist, UBC Sauder School of Business, and a consultant for Genentech, Novartis and several Biotechnology companies. He is a highly cited scientist (303 Career total referred publications and an h-index of 101, with >37,100 citations—including 54 >100-199, 28 >200-499, 11 >500-999, 3 >1,000-1,500, and 1>1,600, including 31 high-impact Nature (1), Science (2), Cell and daughter journal (28) papers, most as senior PI). He has disseminated his lab’s findings by > 259 keynote, plenary and invited talks at international and national conferences, and 235 invited seminars at universities, research institutes and companies. He has trained 40 postdoctoral fellows and graduated 14 Ph.D. and 6 M.Sc. students, with 18 now holding academic appointments: 8 are Full Professors (including 2 Department Chairs), 4 are Associate Professors, and 6 are Assistant Professors. 
He was elected by his peers to organize and Chair the 2003 Matrix Metalloproteinase (MMP) and 2010 Protease Gordon Research Conferences, and in 2017 he was Co-Chair of the International Proteolysis Society Biannual Meeting, the premier conferences of his fields. He holds influential roles on the executive of > 10 international committees, the most prominent of which was being elected to the Human Proteome Organization (HUPO) Executive Council and to Chair the HUPO Chromosome-centric Human Proteome Project (C-HPP). In 2022 he was invited to attend the “G7 Research Summit on One Health” as UBC’s sole representative. He is the recipient of numerous awards e.g., 2006 Killam Faculty Research Prize, Senior Science UBC; 2002 CIHR Researcher of the Year Award; Helmholtz Award (2008); International Proteolysis Society Lifetime Achievement Award (2011); Matrix Biology Society of Australia and New Zealand Barry Preston Award (2012); and the International Association for Dental Research Distinguished Scientist Award (2013). His advances in proteomics have been recognized by the Canadian National Proteomics Network Tony Pawson Award (2014); the Proteomass Scientific Society Award (2017); the highly prestigious 2018 international HUPO Discovery Award in Proteomics Sciences; and the 2022 Helmut Holzer Award. He is an Associate Editor of the Journal of Proteome Research
Overall Laboratory Research Interests 
Professor Chris Overall is a biochemist and molecular biologist with internationally recognised expertise in proteases, proteomics, and inflammation signalling. Only 340/565 human proteases have known substrates and hence biological roles (Nature Reviews Genetics). Recognizing the importance of substrate-binding exosite domains on proteases, I led a team that was the first to use these as substrate ‘baits’ in a yeast two-hybrid screen, at a time when protein disulphide cross-linkages were predicted to exclude two-hybrid screens for extracellular proteins (Science). We showed that MMPs were ill-conceived drug targets as MMPs were tissue protective, in an era when MMPs have always been considered drug targets (Nature Reviews Drug Discovery), by orchestrating neutrophil and macrophage leukocyte responses through coordinate activation/inactivation of virtually all chemokines and complement. Recently we showed that macrophage MMP12 both stimulates, then over time inactivates, anti-viral interferon-α (Nature Medicine) and interferon-γ (Nature Communications), providing feedback which also drives the transition from pro-inflammatory IFN-γ-activated (M1) macrophages to tissue-reparative immunosuppressant (M2) macrophages. more details...