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    Anthony O'Donoghue

    TitleAssistant Professor In Residence
    SchoolUniversity of California, San Diego
    DepartmentSchool of Pharmacy and Pharmaceutical Science
    Address9500 Gilman Drive #0755
    CA La Jolla 92093
    Phone858-534-5360
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      Collapse Biography 
      Collapse Education and Training
      University of California San FranciscoAssociate Specialist2015Pharmaceutical Chemistry
      University of California San FranciscoPost-Doctoral Training2011Pharmaceutical Chemistry
      National University of Ireland, GalwayPh.D2005Biochemistry
      National University of Ireland, GalwayB.S.2000Biochemistry
      Cork Institute of Technology, IrelandNational Diploma1998Cell & Molecular Biology
      Collapse Awards and Honors
      Future Science2013  - 2013Bioanalysis Young Investigator Award
      National University of Ireland, Galway2002  - 2003UC Education Abroad Scholarship

      Collapse Overview 
      Collapse Overview
      My laboratory interests lie in the detection and characterization of proteolytic enzymes that are involved in disease. In particular, we are interested in understanding the role of peptidases/proteases at host-pathogen and tumor-stroma interfaces. Our research utilizes a mass spectrometry based platform technology to uncover the global proteolytic activity in complex biological samples such as the secretions of cancer cells and infectious organisms. Our workflow also includes in-depth proteomic analysis to identify the enzymes. Knowledge of which peptidases are functionally active in diseased tissue and not active in healthy tissue allow us to 1) develop peptidase inhibitors to shut down the function, 2) generate peptidase-activated imaging agents to locate the disease or 3) develop peptidase-activated drugs to aid in the delivery of toxic compounds to the site of disease. Using this technology, we have uncovered novel proteolytic activities in gastric juice, pancreatic cyst fluid, serum and neutrophil extracts. In addition our group is highly collaborative and we routinely generate substrate specificity profiles of endo- and exo-peptidases that have been isolated from diverse organisms that includes ticks, crustaceans and parasitic worms.


      Collapse Research 
      Collapse Research Activities and Funding
      Exploring the proteasome as a new drug target to treat schistosomiasis
      NIH R21AI133393Jun 23, 2017 - May 31, 2019
      Role: Principal Investigator
      Global Profiling of Extracellular Protease Activity from Lung Cancer Cells
      American Cancer Society Institute Research Grant Dec 15, 2016 - Dec 14, 2016
      Role: Principal Investigator
      Global analysis of age-related changes to peptide and protease signaling using patient-derived, age-preserved induced neurons
      UC San Diego Center for Healthy Aging Oct 1, 2016 - Sep 30, 2017
      Role: Principal Investigator
      Rapid Point-of-Care Detection of Candidemia in Serum
      UC San Diego CTRI Apr 1, 2016 - Mar 31, 2017
      Role: Principal Investigator

      Collapse ORNG Applications 
      Collapse Featured Publications
      Collapse Websites

      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Winter MB, La Greca F, Arastu-Kapur S, Caiazza F, Cimermancic P, Buchholz TJ, Anderl JL, Ravalin M, Bohn MF, Sali A, O'Donoghue A, Craik CS. Immunoproteasome functions explained by divergence in cleavage specificity and regulation. Elife. 2017 Nov 28; 6. PMID: 29182146.
        View in: PubMed
      2. Ivry SL, Meyer NO, Winter MB, Bohn MF, Knudsen GM, O'Donoghue A, Craik CS. Global substrate specificity profiling of post-translational modifying enzymes. Protein Sci. 2017 Nov 23. PMID: 29168252.
        View in: PubMed
      3. LaMonte GM, Almaliti J, Bibo-Verdugo B, Keller L, Zou BY, Yang J, Antonova-Koch Y, Orjuela-Sanchez P, Boyle CA, Vigil E, Wang L, Goldgof GM, Gerwick L, O'Donoghue A, Winzeler EA, Gerwick WH, Ottilie S. Development of a Potent Inhibitor of the Plasmodium Proteasome with Reduced Mammalian Toxicity. J Med Chem. 2017 Aug 10; 60(15):6721-6732. PMID: 28696697.
        View in: PubMed
      4. Roncase EJ, Moon C, Chatterjee S, González-Páez GE, Craik CS, O'Donoghue A, Wolan DW. Substrate Profiling and High Resolution Co-complex Crystal Structure of a Secreted C11 Protease Conserved across Commensal Bacteria. ACS Chem Biol. 2017 Jun 16; 12(6):1556-1565. PMID: 28414448.
        View in: PubMed
      5. Ivry SL, Sharib JM, Dominguez DA, Roy N, Hatcher SE, Yip-Schneider MT, Schmidt CM, Brand RE, Park WG, Hebrok M, Kim GE, O'Donoghue A, Kirkwood KS, Craik CS. Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic Cysts. Clin Cancer Res. 2017 Aug 15; 23(16):4865-4874. PMID: 28424202.
        View in: PubMed
      6. Meyer NO, O'Donoghue A, Schulze-Gahmen U, Ravalin M, Moss SM, Winter MB, Knudsen GM, Craik CS. Multiplex Substrate Profiling by Mass Spectrometry for Kinases as a Method for Revealing Quantitative Substrate Motifs. Anal Chem. 2017 Apr 18; 89(8):4550-4558. PMID: 28322550.
        View in: PubMed
      7. Bibo-Verdugo B, Jiang Z, Caffrey CR, O'Donoghue A. Targeting proteasomes in infectious organisms to combat disease. FEBS J. 2017 May; 284(10):1503-1517. PMID: 28122162.
        View in: PubMed
      8. Clarke SC, Dumesic PA, Homer CM, O'Donoghue A, La Greca F, Pallova L, Majer P, Madhani HD, Craik CS. Integrated Activity and Genetic Profiling of Secreted Peptidases in Cryptococcus neoformans Reveals an Aspartyl Peptidase Required for Low pH Survival and Virulence. PLoS Pathog. 2016 Dec; 12(12):e1006051. PMID: 27977806.
        View in: PubMed
      9. O'Donoghue A, Ivry SL, Chaudhury C, Hostetter DR, Hanahan D, Craik CS. Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors. Biol Chem. 2016 Sep 01; 397(9):871-81. PMID: 27149201.
        View in: PubMed
      10. LaRock CN, Todd J, LaRock DL, Olson J, O'Donoghue A, Robertson AA, Cooper MA, Hoffman HM, Nizet V. IL-1ß is an innate immune sensor of microbial proteolysis. Sci Immunol. 2016 Aug; 1(2). PMID: 28331908.
        View in: PubMed
      11. LaRock CN, Todd J, LaRock DL, Olson J, O'Donoghue A, Robertson AAB, Cooper MA, Hoffman HM, Nizet V. IL-1ß is an innate immune sensor of microbial proteolysis. Sci Immunol. 2016 Aug 19; 1(2):eaah3539. PMID: 28783696.
        View in: PubMed
      12. Goupil LS, Ivry SL, Hsieh I, Suzuki BM, Craik CS, O'Donoghue A, McKerrow JH. Cysteine and Aspartyl Proteases Contribute to Protein Digestion in the Gut of Freshwater Planaria. PLoS Negl Trop Dis. 2016 Aug; 10(8):e0004893. PMID: 27501047; PMCID: PMC4976874.
      13. Lentz CS, Ordonez AA, Kasperkiewicz P, La Greca F, O'Donoghue A, Schulze CJ, Powers JC, Craik CS, Drag M, Jain SK, Bogyo M. Design of Selective Substrates and Activity-Based Probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis. ACS Infect Dis. 2016 Nov 11; 2(11):807-815. PMID: 27739665.
        View in: PubMed
      14. Julien O, Zhuang M, Wiita AP, O'Donoghue A, Knudsen GM, Craik CS, Wells JA. Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. Proc Natl Acad Sci U S A. 2016 Apr 05; 113(14):E2001-10. PMID: 27006500; PMCID: PMC4833263 [Available on 10/05/16].
      15. Li H, O'Donoghue A, van der Linden WA, Xie SC, Yoo E, Foe IT, Tilley L, Craik CS, da Fonseca PC, Bogyo M. Structure- and function-based design of Plasmodium-selective proteasome inhibitors. Nature. 2016 Feb 11; 530(7589):233-6. PMID: 26863983; PMCID: PMC4755332.
      16. Bibo-Verdugo B, O'Donoghue A, Rojo-Arreola L, Craik CS, García-Carreño F. Complementary Proteomic and Biochemical Analysis of Peptidases in Lobster Gastric Juice Uncovers the Functional Role of Individual Enzymes in Food Digestion. Mar Biotechnol (NY). 2016 Apr; 18(2):201-14. PMID: 26613762.
        View in: PubMed
      17. Dvorák J, Fajtová P, Ulrychová L, Leontovyc A, Rojo-Arreola L, Suzuki BM, Horn M, Mareš M, Craik CS, Caffrey CR, O'Donoghue A. Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles. Biochimie. 2016 Mar; 122:99-109. PMID: 26409899; PMCID: PMC4747843 [Available on 03/01/17].
      18. O'Donoghue A, Knudsen GM, Beekman C, Perry JA, Johnson AD, DeRisi JL, Craik CS, Bennett RJ. Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus destructans, the causative agent of white-nose syndrome. Proc Natl Acad Sci U S A. 2015 Jun 16; 112(24):7478-83. PMID: 25944934.
        View in: PubMed
      19. Sharma V, Panwar P, O'Donoghue A, Cui H, Guido RV, Craik CS, Brömme D. Structural requirements for the collagenase and elastase activity of cathepsin K and its selective inhibition by an exosite inhibitor. Biochem J. 2015 Jan 01; 465(1):163-73. PMID: 25279554.
        View in: PubMed
      20. O'Donoghue A, Jin Y, Knudsen GM, Perera NC, Jenne DE, Murphy JE, Craik CS, Hermiston TW. Global substrate profiling of proteases in human neutrophil extracellular traps reveals consensus motif predominantly contributed by elastase. PLoS One. 2013; 8(9):e75141. PMID: 24073241; PMCID: PMC3779220.
      21. Corvo I, O'Donoghue A, Pastro L, Pi-Denis N, Eroy-Reveles A, Roche L, McKerrow JH, Dalton JP, Craik CS, Caffrey CR, Tort JF. Dissecting the active site of the collagenolytic cathepsin L3 protease of the invasive stage of Fasciola hepatica. PLoS Negl Trop Dis. 2013; 7(7):e2269. PMID: 23875031; PMCID: PMC3708847.
      22. O'Donoghue A, Hua S, Meyer B, Ros A. Bioanalysis Young Investigator Award 2013. Bioanalysis. 2013 Jul; 5(13):1617-21. PMID: 23822125.
        View in: PubMed
      23. Small JL, O'Donoghue A, Boritsch EC, Tsodikov OV, Knudsen GM, Vandal O, Craik CS, Ehrt S. Substrate specificity of MarP, a periplasmic protease required for resistance to acid and oxidative stress in Mycobacterium tuberculosis. J Biol Chem. 2013 May 03; 288(18):12489-99. PMID: 23504313; PMCID: PMC3642297.
      24. O'Donoghue A, Eroy-Reveles AA, Knudsen GM, Ingram J, Zhou M, Statnekov JB, Greninger AL, Hostetter DR, Qu G, Maltby DA, Anderson MO, Derisi JL, McKerrow JH, Burlingame AL, Craik CS. Global identification of peptidase specificity by multiplex substrate profiling. Nat Methods. 2012 Nov; 9(11):1095-100. PMID: 23023596; PMCID: PMC3707110.
      25. Sojka D, Franta Z, Frantová H, Bartosová P, Horn M, Váchová J, O'Donoghue A, Eroy-Reveles AA, Craik CS, Knudsen GM, Caffrey CR, McKerrow JH, Mares M, Kopácek P. Characterization of gut-associated cathepsin D hemoglobinase from tick Ixodes ricinus (IrCD1). J Biol Chem. 2012 Jun 15; 287(25):21152-63. PMID: 22539347; PMCID: PMC3375538.
      26. Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K, Hernandez H, Jang GM, Roth SL, Akiva E, Marlett J, Stephens M, D'Orso I, Fernandes J, Fahey M, Mahon C, O'Donoghue A, Todorovic A, Morris JH, Maltby DA, Alber T, Cagney G, Bushman FD, Young JA, Chanda SK, Sundquist WI, Kortemme T, Hernandez RD, Craik CS, Burlingame A, Sali A, Frankel AD, Krogan NJ. Global landscape of HIV-human protein complexes. Nature. 2011 Dec 21; 481(7381):365-70. PMID: 22190034; PMCID: PMC3310911.
      27. Mahon CS, O'Donoghue A, Goetz DH, Murray PG, Craik CS, Tuohy MG. Characterization of a multimeric, eukaryotic prolyl aminopeptidase: an inducible and highly specific intracellular peptidase from the non-pathogenic fungus Talaromyces emersonii. Microbiology. 2009 Nov; 155(Pt 11):3673-82. PMID: 19556294; PMCID: PMC2888130.
      28. O'Brien TC, Mackey ZB, Fetter RD, Choe Y, O'Donoghue A, Zhou M, Craik CS, Caffrey CR, McKerrow JH. A parasite cysteine protease is key to host protein degradation and iron acquisition. J Biol Chem. 2008 Oct 24; 283(43):28934-43. PMID: 18701454; PMCID: PMC2570886.
      29. O'Donoghue A, Mahon CS, Goetz DH, O'Malley JM, Gallagher DM, Zhou M, Murray PG, Craik CS, Tuohy MG. Inhibition of a secreted glutamic peptidase prevents growth of the fungus Talaromyces emersonii. J Biol Chem. 2008 Oct 24; 283(43):29186-95. PMID: 18687686; PMCID: PMC2570871.
      30. Cuetara BL, Crotti TN, O'Donoghue A, McHugh KP. Cloning and characterization of osteoclast precursors from the RAW264.7 cell line. In Vitro Cell Dev Biol Anim. 2006 Jul-Aug; 42(7):182-8. PMID: 16948499; PMCID: PMC2883882.
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