Overall, Christopher

Professor Christopher Overall is a Full Professor, a Distinguished University Scholar, and Canada Research Chair Laureate in Protease Proteomics and Systems Biology at the University of British Columbia; an Honorary Professor at Albert-Ludwigs Universität Freiburg, Germany (2014–), and a Yonsei Distinguished Scholar of Yonsei University, Republic of Korea (2023–). He was a Senior Fellow of the Freiburg Institute of Advanced Studies, Albert-Ludwigs Universität Freiburg, Germany (2010–2013) and a Tier 1 Canada Research Chair in Protease Proteomics and Systems Biology (2001–2022). Dr Overall was inducted as a fellow into the Royal Society of Canada (FRASC) Academy of Science in 2018 and the Canadian Academy of Health Sciences (FCAHS) in 2005.

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 training with Dr. Michael Smith, Nobel Laureate, Biotechnology Laboratory, UBC.  He launched his lab at UBC in 1993. 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. He is now a Creative Destruction Lab Scientist at the UBC Sauder School of Business, and a consultant for Genentech, Novartis and several Biotechnology companies.

Chris 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, and now in One Health Strategies for investigation of viral zoonosis.  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.

He is a highly cited scientist (308 Career total, with an h-index = 105 and >39,300 citations—including 66 >100 – 199, 27 >200 – 499, 13 >500 – 999, 3 >1,000 – 1,500, and 1 >1,650, including 30 high-impact Nature (1), Science (2), Cell and daughter journal (27) papers, most as senior PI. He has disseminated his lab’s findings by > 266 keynote, plenary and invited talks at international and national conferences, and 236 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 20 now holding academic appointments: 9 are Full Professors (including 2 Department Chairs), 5 are Associate Professors, and 6 are Assist. Professors. Chris was awarded the UBC 2022 John McNeill Excellence in Health Research Mentorship Award.

His peers elected Dr. Overall to organize and Chair the 2003 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 to represent UBC. He is the recipient of numerous recognitions, e.g., election to the Royal Society of Canada; a Distinguished Scholar of UBC in 2023; a Yonsei Distinguished Scholar of Yonsei University (2023). He received the UBC 2006 Killam Faculty Research Prize; 2002 CIHR Researcher of the Year; and the Helmholtz Award (2008); International Proteolysis Society Lifetime Achievement Award (2011); Matrix Biology Society of Australia and New Zealand Barry Preston Award (2012); and the IADR 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 2018 Human Proteome Organization (HUPO) Discovery Award in Proteomics Sciences; and the 2022 Helmut Holzer Award. He is a Councillor of 1^st p-Hub Global Proteomics Project, Guangzhou, China. He has presented >277 keynote, plenary and invited talks at international and national conferences, and 240 invited seminars at universities, research institutes, and companies.

Professor Christopher M. Overall was awarded the 2022 Helmut Holzer Award, an honour recognizing outstanding contributions to the advancement of the field of proteolysis.

The Award, sponsored by The International Union of Biochemistry and Molecular Biology, was presented September 18 at the opening plenary lecture of the September 19 – 22, 2022 Federation of European Biochemical Societies conference “Proteolysis at the Interface between Health and Disease,” in Bled, Slovenia. Dr. Overall’s lecture was entitled. “Pathobiology of COVID-19 Deciphered by TAILS Analysis of SARS CoV-2 3CLpro Substrates.”

Dr. Helmut Holzer (1921-1997) served as chairman of the Scientific Society of Freiburg for 25 years. The award in his honour was established after his death in 1997.

Dr. Overall reports that in a happy coincidence, he was an external senior fellow at the Freiburg Institute of Advanced Studies (FRIAS), School of Life Sciences – LifeNet, Albert-Ludwigs Universität Freiburg, Freiburg, Germany, where he is now an honorary professor. At UBC, Dr. Overall is a professor in the Faculty of Dentistry, Department of Oral Biological and Medical Sciences, and is also affiliated with the Departments of Biochemistry and Molecular Biology, Obstetrics and Gynecology, and is a member of the Centre for Blood Research, where he has his research team and laboratory.

Research Interests of Dr. Christopher M. Overall, BDS, BSc(Hons), MDS, PhD, FCAHS, FRSC

Numbers refer to the asterisked 20 Significant publications from his curriculum vitae.

As a highly awarded and productive Tier 1 Canada Research Chair Laureate, Professor Overall pioneered breakthroughs in developing innovative approaches and mass spectrometry proteomic techniques to identify proteolytic signatures that decipher disease mechanisms in vivo. He is best known for two related but distinct scientific achievements.  The first is his development of new methods for the global discovery of protease substrates to investigate proteolysis in vivo.  The most notable of these are cutting-edge proteomic techniques^18,20, which allowed the unbiased identification of protease cleavage sites and substrates in vivo for the first time.  Thereby, he established the field of degradomics (Nature Reviews Molecular Cell Biology).  The second is leveraging these techniques to reveal new and often unexpected biological roles for proteases and their cleaved substrates in vivo in normal tissues and their aberrations in disease.  Especially noteworthy was his demonstration that matrix metalloproteinases (MMPs) proteolytically process virtually all 54 leukocyte chemoattractant cytokines known as chemokines.  Processing either activates, converts other chemokines to antagonists, or leads to cell membrane shedding^12-14—a paradigm shift in which, rather than just degrading extracellular matrix, MMPs are now recognized to dampen inflammation, culminating in the restoration of tissue homeostasis.  This has had broad implications for drug targeting and has resolved perplexing results on drug side effects (Nature Reviews Cancer) and his lab is at the forefront in formulating concepts on the roles of proteolysis in disease and their interplay in the control of cell signalling pathways.

Professor Overall has published 308 papers, including 30 high-impact Nature (1), Science (2), and daughter journal (27) papers, most as senior PI.  His papers are highly cited (h-index of 105, >39,000 citations, Google Scholar).  He has trained 40 postdoctoral fellows and graduated 15 Ph.D. and 5 M.Sc. students.  As reflected by publication quality and academic placements, he mentored his trainees to achieve their best, with 9 now Full Professors (2 are Department Chairs), 5 Associate Professors, and 8 Assistant Professors — many in European universities. In recognition of his inspiring mentoring, Dr. Overall was awarded the University of British Columbia (UBC) 2022 John McNeill Excellence in Health Research Mentorship Award and in 2023 was recognised as a Distinguished University Scholar.

Dr Overall holds influential roles on the executive of >10 international committees and his peers elected him to organize and Chair the 2003 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.  International recognition of Professor Overall’s advances in both proteomics and systems biology is reflected by his election as Chair of the Human Proteome Organization (HUPO) Chromosome-Centric Human Proteome Project (HPP), which published the high-stringency draft of the human proteome in Nature Communications in 2020: he was the only Canadian listed in the authors. In 2022, he was invited to attend the G7 Research Summit on One Health to represent UBC. He is the recipient of numerous recognitions, e.g., election to the Royal Society of Canada; the UBC 2006 Killam Faculty Research Prize; 2002 CIHR Researcher of the Year; and awards including the Helmholtz (2008); International Proteolysis Society Lifetime Achievement (2011); Matrix Biology Society of Australia and New Zealand Barry Preston (2012); and the IADR 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 2018 HUPO Discovery Award in Proteomics Sciences; and the 2022 Helmut Holzer Award. He has presented >277 keynote, plenary and invited talks at international and national conferences, and >240 invited seminars at universities, research institutes, and companies.

Professor Overall has invented a suite of approaches and techniques, and developed software ^4,11,16 for the comprehensive analysis of proteases and their inhibitors on a system-wide scale.  Only 340/565 human proteases (Nature Reviews Genetics) have known substrates and hence biological roles(Nature Reviews Molecular Cell Biology).  Recognizing the importance of substrate-binding exosite domains on proteases, we were the first to use these as substrate ‘baits’ in a yeast two-hybrid screen¹⁴ (Science)—at a time when protein disulphide cross-linkages were predicted to exclude the yeast two-hybrid approach for extracellular proteins.  We showed that this was not a limitation in this yeast system with a paradigm shift that MMPs are tissue-protective by orchestrating neutrophil and macrophage leukocyte responses through activation/inactivation of virtually all chemoattractant cytokines known as chemokines^12-14, and in subsequent research, by a slew of other cytokines^5,6 and binding proteins, and serpin inhibitors.

Defining protease substrate cleavage-site specificity is central to protease characterization and linkage to substrates.  In this way, we developed the only peptide library technique to simultaneously identify both the amino (P) and carboxyl (P’) amino acid residues flanking the cleavage site—Proteomic Identification of Cleavage Specificity (PICS)¹⁸ (Nature Protocols; Nature Biotechnology).  In one application of PICS, we reported >4,300 cleavage sites in the MMP family, leading to structural insight of their active sites¹⁹. In another study⁷ (Nature Communications), we identified >1000 cleavage sites by an unsuspected active metallopeptidase insertion in bacterial flagellin, the monomer of bacterial flagella that propels bacteria through biofilms and tissues. These metalloproteinase-bearing flagellin molecules assemble proteolytically active flagella (~20 µm) in >200 diverse bacterial species, e.g., the pathogen Clostridium haemolyticum.

In conventional proteomics sample preparation for mass spectrometry, 100,000s of trypsin-generated peptides of a proteome dominated by abundant proteins dilute the terminal peptides of protein N- and C-ends and protease-generated ‘neo’-termini, rendering cleaved peptides rarely detectable.  This is especially problematic for low-abundant transcription factors and signalling proteins like chemokines, cytokines, and antiviral interferons, impairing insight into disease-relevant proteolytic events.  Our technique, Terminal Amino Isotopic Labelling of Substrates (TAILS)²⁰, circumvents these issues in a simple but powerful high-throughput method.  TAILS purifies protein N-terminal peptides and cleaved neo-N-terminal peptides using innovative polymers-for-proteomics to simultaneously identify protease cleavage sites and substrates in native proteomes (Nature Biotechnology; Nature Protocols). The end fragments of the cut proteins are extremely useful as unique biomarkers to monitor disease activity.

Protein C-termini are difficult to label chemically en route to identification, which is further hampered by their absence of basic residues following trypsin digestion.  We discovered a new proteasein Archaea, LysargiNase^TM, to address this¹⁵ (Nature Methods).  LysargiNase-digested proteins release C-terminal peptides that retain an N-terminal lysine or arginine, enabling their ready detection in shotgun proteomics analyses or with higher coverage achieved by C-terminal peptide enrichment by our C-TAILS technique¹⁷ (Nature Methods).

To specifically analyse natural and neo-termini, the Overall Lab developed publicly available software:  WebPICS, CLIPPER, and the Termini-orientated protein Function INferred Database (TopFIND v4.1)¹⁶ (Nature Methods) with >290K termini/>33K cut-sites, receiving >4K hits p.a.  PathFINDer and TopFINDer map substrates to protease pathways, which revealed a highly connected protease network in humans¹¹ (PLoS Biology)—so also highlighting the problems in interpreting knockout or over expression studies, as well as in drug targeting of proteases.

Fundamental to understanding zoonotic virus pathobiology, by a One Health approach, the Overall Lab applied these techniques to discover >300 host cell substrates for the SARS-CoV-2 3CL^pro, main protease¹ (Cell Reports). Cleavage of these leads to inactivation, cytoplasmic localization of nuclear proteins, immune escape, viral transmission, and other regulatory pathways. Thereby, we discovered that the lectin, galectin-8, is a novel intracellular sensor of SARS-CoV-2, but cleavage by SARS-CoV-2 3CL^pro defeats autophagic destruction of galectin-8-tagged virus.

Employing degradomics, we have mechanistically dissected the crosstalk between proteolytic pathways in skin inflammation⁸ (Science Signaling), lysosomal proteases in pancreatic cancer⁹ (Cell Reports), MMP2 in HIV-Associated Dementia¹⁰ (Nature Neuroscience), anti-inflammatory activities of macrophage MMP12 in arthritis¹⁰ (Cell Reports) and in autoimmunity, including lupus⁶ (Nature Communications), and MMP12’s unexpected potent antiviral roles⁵ (Nature Medicine).  In this latter work, we made a remarkable discovery that secreted MMP12 is a ‘moonlighting’ protease (Nature Reviews Drug Discovery) that re-enters cells and traffics to the nucleus as a novel transcription factor regulating ~200 genes.  By increasing transcription of IB—an inhibitor of the pro-inflammatory NFB—we found MMP12 was indispensable for IFN secretion.  We further identified multiple substrates of MMP12 whose gene transcription was repressed by nuclear MMP12—thereby demonstrating concerted dual-negative regulation of both protein substrates and their genes—highlighting a novel mechanism of rapid cellular inhibition and removal of targeted cellular antiviral defence substrates.

In related work, we found that macrophage MMP12 first stimulates secretion, then over time inactivates anti-viral interferon-⁵ (Nature Medicine).  MMP12 also inactivates interferon- by removing the receptor binding site⁶ (Nature Communications), providing feedback that drives the transition from pro-inflammatory IFN--activated macrophages (formerly termed “M1”) to tissue-reparative immunosuppressant (“M2”) macrophages. In discovering new and major roles of MMPs in the regulation of signalling proteins, our studies reveal deeper complexity in the regulation of the extracellular matrix and the cell signalling environment than mere degradation.

In a ground breaking example of clinical application, Professor Overall explored the roles of the intracellular protease MALT1, an essential transducer in lymphocyte antigen receptor signalling and immune activation² (Nature Communications).  Our team found that independent of proteolytic cleavage, non-proteolytic protein-protein interactions by MALT1 initiates NFB activation, whereas, at late stages of NFB activation, MALT1 cleaves HOIL1 in the Linear Ubiquitin Assembly Complex (LUBAC) to downregulate essential linear ubiquitination of pathway mediators to halt NFB signalling².  By developing GO-2-Substrates⁴, we recently predicted and validated more than half of the known MALT1 substrates⁴, Thereby, we upended the concept that MALT1 is solely an enhancer of antigen-driven signalling—with far-reaching consequences for our understanding of immunobiology that has major implications in MALT1 drug targeting for lymphomas.  The multidisciplinary team we assembled also reported in Nature Chemical Biology³ the development of a series of potent nanomolar allosteric inhibitors of MALT1 that bind at Trp580, the same site as an immunodeficient patient’s MALT1 Trp580Ser mutation.  Greatly diminished levels of the mutant MALT1 led to ~50% reduced NFB signalling and immunodeficiency.  In an elegant use of chemical biology, we then found that treatment with this inhibitor rescued protein stability of the mutant MALT1, restoring MALT protein levels to normal in the patient’s lymphocytes.  Moreover, inhibitor treatment also rescued NFB and JNK signalling in the patient’s B and T lymphocytes as well as substrate cleavage upon inhibitor washout.  Thus, a new low molecular weight pharmacological molecular corrector rescues an enzyme deficiency by substituting for the mutated residue, inspiring precision therapies to increase mutant enzyme activity and for treating similar molecularly-defined human disorders.

Comprehensive List

• Google Scholar
• Lab Website
• PubMed

Most Significant Publications

1. *  Pablos, I., Machado, Y., de Jesus, H.C.R., Mohamud, Y., Kappelhoff, R., Lindskog, C., Vlok, M., Bell, P.A, Butler, G.S., Grin, P.M., Cao, Q.T., Nguyen, J.P., Solis, N., Abbina, S., Rut, W., Vederas, J.C., Szekely, L., Szakos, A., Drag, M., Kizhakkedathu, J., Mossman, K., Hirota, J., Jan, E., Lou, H., Banerjee, A., and Overall, C.M. 2021. Mechanistic Insights into COVID-19 by Global Analysis of the SARS-CoV-2 3CL^pro Substrate Degradome. Cell Reports 37, Oct 26;37(4):109892. doi: 10.1016/j.celrep.2021.109892. Citations as of Sep. 1, 2023:  54
2. *  Klein, T., Fung, S.Y., Renner, F., Blank, M.A., Dufour, A., Kang, S., Bolger-Munro, M., Scurll, J.M., Priatel, J.J., Schweigler, P., Melkko, S., Gold, M.S., Viner, R.I., Régnier, C.H., Turvey, S.E., and Overall, C.M. 2015. The Paracaspase MALT1 Cleaves HOIL1 Reducing Linear Ubiquitination by LUBAC to Dampen Lymphocyte NF-κB Signalling. Nature Communications 6, 8777, 1 – 17. doi:10.1038/ncomms9777. Featured Article and Featured in Nature Immunology; Highlighted by Faculty of 1000 as a high significance paper. Citations as of Sep. 1, 2023:  147
3. *  Quancard, J., Klein, T., Fung, S-Y., Renatus, M., Hughes, N., Israël, L., Priatel, J.J., Kang, S., Blank, M.A., Viner, R.I., Blank, J., Schlapbach, A., Erbel, P., Kizhakkedathu, J., Villard, F., Hersperger, R., Turvey, S.E., Eder, J., Bornancin, F., and Overall, C.M. 2019. An Allosteric MALT1 Inhibitor is a Molecular Corrector Rescuing Function in an Immunodeficient Patient.
   Nature Chemical Biology 15, 304 – 313. Citations as of Sep. 1, 2023:  49
4. *  Bell, P.A., Scheuermann, S., Renner, F., Pan, C.L., Lu, H.Y., Turvey, S.E., Bornancin, F., Régnier, C.H., and Overall, C.M. 2022. Integrating Knowledge of Protein Sequence with Protein Function for the Prediction and Validation of New MALT1 Substrates. Computational and Structural Biotechnology Journal 20, 4,717 – 4,732 Citations as of Sep. 1, 2023:  5
5. *  Marchant, D.J., Bellac, C., Moraes, T.J., Wadsworth, S.J., Dufour, A., Butler, G.S., Bilawchuk, L.M., Hendry, R.G., Robertson, A.G., Cheung, C.T., Ng, J., Ang, L., Luo, Z., Heilbron, K., Norris, M.J., Duan, W., Bucyk, T., Karpov, A., Devel, L., Georgiadis, D., Hegele, R.G., Luo, H., Granville, D.J., Dive, V., McManus, B.M., and Overall, C.M. 2014. A New Transcriptional Role for Matrix Metalloproteinase-12 in Antiviral Immunity. Nature Medicine 20, 493 – 502. doi: 10.1038/nm.3508. Featured Article in News and Views. Citations as of Sep. 1, 2023:  243
6. *  Dufour, A., Bellac, C.L, Eckhard, U., Solis, N., Klein, T., Kappelhoff, R., Fortelny, N., Jobin, P., Rozmus, J., Mark, J., Pavlidis, P., Dive, V., Barbour, S.J., and Overall, C.M. 2018. C-Terminal Truncation of IFN-γ Inhibits Proinflammatory Macrophage Responses and is Deficient in Autoimmune Disease.
   Nature Communications 9, 2416, 1 – 18. doi: 10.1038/s41467-018-04717-4.
   Citations as of Sep. 1, 2023:  58.
7. *  Eckhard, U., Bandukwala, H., Mansfield, M.J., Marino, G., Cheng, J., Wallace, I., Holyoak, T., Charles, T.C., Austin, J., Overall, C.M.^, and Doxey, A.C.^ 2017. Discovery of a Proteolytic Flagellin Family in Diverse Bacterial Phyla that Assembles Enzymatically Active Flagella.
   Nature Communications 8, 521, 1 – 9. doi: 10.1038/s41467-017-00599-0. ^Joint Shared Senior Authors. Citations as of Sep. 1, 2023:  37
8. *  auf dem Keller, U., Prudova, A., Eckhard, U., Fingleton, B., and Overall, C.M. 2013. Systems-Level Analysis of Proteolytic Events in Increased Vascular Permeability and Complement Activation in Skin Inflammation. Science Signalling 6: rs2, 1 – 15.doi: 10.1126/scisignal.2003512. Featured cover.
     Citations as of Sep. 1, 2023:  102
9. *  Prudova, A., Gocheva, V., auf dem Keller, U., Eckhard, U., Olson, O., Akkari, L., Butler, G.S., Fortelny, N., Lange, P.F., Mark, J., Joyce, J., and Overall, C.M. 2016. TAILS N-Terminomics and Proteomics Show Protein Degradation Dominates Over Proteolytic Processing by Cathepsins in Pancreatic Tumors.
   Cell Reports 16, 1,762 – 1,773.Featured cover. Citations as of Sep. 1, 2023:  70
10. *  Zhang, K., McQuibban, G.A., Silva, C., Butler, G.S., Johnston, J.B., Holden, J., Clark-Lewis, I., Overall, C.M.^, and Power, C.^ 2003. HIV-Induced Metalloproteinase Processing of the Chemokine Stromal Cell Derived Factor-1 Causes Neurodegeneration. ^Joint Senior and Communicating Authors.
    Nature Neuroscience 6, 1064 – 1071. Citations as of Sep. 1, 2023:  363
11. *  Bellac, C.L., Dufour, A., Krisinger, M.J., Loonchanta, A., Starr, A.E., auf dem Keller, U., Lange, P.F., Goebeler, V., Kappelhoff, R., Butler, G.S., Burtnick, L.D., Conway, E.M., Roberts, C.R., and Overall, C.M. 2014. Macrophage Matrix Metalloproteinase-12 Dampens Inflammation and Neutrophil Influx in Arthritis.
    Cell Reports 9, 618 – 632. Citations as of Sep. 1, 2023:  103
12. *  Fortelny, N., Cox, J.H., Kappelhoff, R., Starr, A.E., Lange, P.F., Pavlidis, P., and Overall, C.M. 2014. Network Analyses Reveal Pervasive Functional Regulation Between Proteases in the Human Protease Web. PLoS Biology 12, e1001869. doi: 10.1371/journal.pbio.1001869. Featured Weekly Editors Pick.
    Citations as of Sep. 1, 2023:  160
13. *  Dean, R.A., Cox, J.H., Bellac, C.L., Doucet, A., Starr, A.E., and Overall, C.M. 2008. Macrophage-Specific Metalloelastase (MMP-12) Truncates and Inactivates ELR⁺ CXC Chemokines and Generates CCL2, 7, 8, and 13 Antagonists:  Potential Role of the Macrophage in Terminating PMN Influx.
    Blood 112, 3444 – 3453. Citations as of Sep. 1, 2023:  272
14. *  McQuibban, G.A., Gong, J.-H., Tam, E., McCulloch, C.A.G., Clark-Lewis, I., and Overall, C.M. 2000. Inflammation Dampened by Gelatinase A Cleavage of Monocyte Chemoattractant Protein-3.
    Science 289, 1202 – 1206. Selected by the Faculty of 1000 Biology for its significance.
    Citations as of Sep. 1, 2023:  944
15. *  Huesgen, P.F., Lange, P.F., Rogers, L.D., Solis, N., Eckhard, U., Kleifeld, O., Goulas, T., Gomis-Rüth, F.X., and Overall, C.M. 2015. LysargiNase Mirrors Trypsin for Protein C-Terminal and Methylation-Site Identification. Nature Methods 12, 55 – 58. Citations as of Sep. 1, 2023:  139
16. *  Lange, P. and Overall, C.M. 2011. TopFIND, a Knowledgebase Linking Protein Termini with Function. Nature Methods 8, 703 – 704. Citations as of Sep. 1, 2023:  95
17. *  Schilling, O., Barré, O., Huesgen, P.F., and Overall, C.M. 2010. Proteome-Wide Analysis of Protein Carboxy Termini: C Terminomics. Nature Methods 7, 508 – 511. Featured in C&EN (Chemical & Engineering News). Citations as of Sep. 1, 2023: 157
18. *  Kleifeld, O., Doucet, A., auf dem Keller, U., Prudova, A., Schilling, O., Kainthan, R.K., Starr, A., Foster, L.J., Kizhakkedathu, J.N., and Overall, C.M. 2010. Isotopic Labelling of Terminal Amines in Complex Samples Identifies Protein N-Termini and Protease Cleavage Products.
    Nature Biotechnology 28,281 – 288. Citations as of Sep. 1, 2023: 530
19. *  Eckhard, U., Huesgen, P.F., Schilling, O., Bellac, C.L., Butler, G.S., Cox, J.H., Dufour, A., Goebeler, V., Kappelhoff, R., auf dem Keller, U., Klein, T., Lange, P.L., Marino, G., Morrison, C.J., Prudova, A., Rodriguez, D., Starr, A.E., Wang, Y., and Overall, C.M. 2016. Active Site Specificity Profiling of the Matrix Metalloproteinase Family: Proteomic Identification of 4,300 Cleavage Sites by Nine MMPs Explored with Structural and Synthetic Peptide Cleavage Analyses. Matrix Biology 49, 37 – 60.
      Citations as of Sep. 1, 2023:  195
20. *  Schilling, O. and Overall, C.M. 2008. Proteome-Derived Database-Searchable Peptide Libraries for Identifying Protease Cleavage Sites. Nature Biotechnology 26, 685 – 694. Designated in the Exceptional Category by the Faculty of 1000 Biology for its significance. Citations as of Sep. 1, 2023:  418