Matthew Bogyo

Honors and Awards

• Investigator in Pathogenesis of Infectious Disease, Burroughs Wellcome (May 2005)
• Terman Fellow, Stanford University (2003)
• Searle Scholar, Searle Scholars Program (2004)

Professional Education

• B.S., Bates College Chemistry (1993)
• Ph.D., MIT Biochemistry (1997)

Postdoctoral Advisees

• Victoria Albrow, Paul Bowyer, Edgar Deu Sandoval, Jiyoun Lee, Montserrat Morell Fernandez, Margot Paulick, Elizabeth Ponder, Aimee Shen, Martijn Verdoes, Fangfang Yin

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Microbiology and Immunology
• Chemical and Systems Biology

Web Site Links

• Bogyo Lab Main Site

Research Interests

Our lab uses chemical, biochemical, and cell biological methods to study protease function in human disease. Projects include:

1) Design and synthesis of novel chemical probes for each of the primary protease families.

2) Understanding the role of proteolysis in the life cycle of the human parasites, Plasmodium falciparum and Toxoplasma gondii.

3) Defining the specific functional roles of proteases during the process of tumorogenesis.

4) In vivo imaging of protease activity

Publications

• Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum. Arastu-Kapur S,  Ponder EL, Fonovi? UP, Yeoh S, Yuan F, Fonovi? M, Grainger M, Phillips CI, Powers JC, Bogyo M.  Nat Chem Biol.  2008; 4 (3): 203-13
• Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Blum G,  von Degenfeld G, Merchant MJ, Blau HM, Bogyo M.  Nat Chem Biol.  2007; 3 (10): 668-77
• Design, synthesis, and evaluation of in vivo potency and selectivity of epoxysuccinyl-based inhibitors of papain-family cysteine proteases. Sadaghiani AM,  Verhelst SH, Gocheva V, Hill K, Majerova E, Stinson S, Joyce JA, Bogyo M.  Chem Biol.  2007; 14 (5): 499-511
• A selective activity-based probe for the papain family cysteine protease dipeptidyl peptidase I/cathepsin C. Yuan F,  Verhelst SH, Blum G, Coussens LM, Bogyo M.  J Am Chem Soc.  2006; 128 (17): 5616-7
• Identification of early intermediates of caspase activation using selective inhibitors and activity-based probes. Berger AB,  Witte MD, Denault JB, Sadaghiani AM, Sexton KM, Salvesen GS, Bogyo M.  Mol Cell.  2006; 23 (4): 509-21
• Dynamic imaging of protease activity with fluorescently quenched activity-based probes. Blum G,  Mullins SR, Keren K, Fonovic M, Jedeszko C, Rice MJ, Sloane BF, Bogyo M.  Nat Chem Biol.  2005; 1 (4): 203-9
• Activity-based probes that target diverse cysteine protease families. Kato D,  Boatright KM, Berger AB, Nazif T, Blum G, Ryan C, Chehade KA, Salvesen GS, Bogyo M.  Nat Chem Biol.  2005; 1 (1): 33-8
• Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Joyce JA,  Baruch A, Chehade K, Meyer-Morse N, Giraudo E, Tsai FY, Greenbaum DC, Hager JH, Bogyo M, Hanahan D.  Cancer Cell.  2004; 5 (5): 443-53
• A role for the protease falcipain 1 in host cell invasion by the human malaria parasite. Greenbaum DC,  Baruch A, Grainger M, Bozdech Z, Medzihradszky KF, Engel J, DeRisi J, Holder AA, Bogyo M.  Science.  2002; 298 (5600): 2002-6
• Evaluation of alpha,beta-unsaturated ketone-based probes for papain-family cysteine proteases. Yang Z,  Fonovi? M, Verhelst SH, Blum G, Bogyo M.  Bioorg Med Chem.  2009; 17 (3): 1071-8
• Metabolomics cuts to the chase to chase the cuts. Bogyo M,  Nat Chem Biol.  2009; 5 (1): 5-6
• Activity-based probes as a tool for functional proteomic analysis of proteases. Fonovi? M,  Bogyo M.  Expert Rev Proteomics.  2008; 5 (5): 721-30
• Small molecule-induced allosteric activation of the Vibrio cholerae RTX cysteine protease domain. Lupardus PJ,  Shen A, Bogyo M, Garcia KC.  Science.  2008; 322 (5899): 265-8
• Friend or foe? Turning a host defense protein into a pathogen's accomplice. Shen A,  Bogyo M.  Chem Biol.  2008; 15 (9): 879-80
• Trial of the cysteine cathepsin inhibitor JPM-OEt on early and advanced mammary cancer stages in the MMTV-PyMT-transgenic mouse model. Schurigt U,  Sevenich L, Vannier C, Gajda M, Schwinde A, Werner F, Stahl A, von Elverfeldt D, Becker AK, Bogyo M, Peters C, Reinheckel T.  Biol Chem.  2008; 389 (8): 1067-74
• Application of activity-based probes to the study of enzymes involved in cancer progression. Paulick MG,  Bogyo M.  Curr Opin Genet Dev.  2008; 18 (1): 97-106
• Maturation of dendritic cells depends on proteolytic cleavage by cathepsin X. Obermajer N,  Svajger U, Bogyo M, Jeras M, Kos J.  J Leukoc Biol.  2008; 84 (5): 1306-15
• Insulin-like growth factor II receptor-mediated intracellular retention of cathepsin B is essential for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus. Rose PP,  Bogyo M, Moses AV, Früh K.  J Virol.  2007; 81 (15): 8050-62
• Proteomics evaluation of chemically cleavable activity-based probes. Fonovi? M,  Verhelst SH, Sorum MT, Bogyo M.  Mol Cell Proteomics.  2007; 6 (10): 1761-70
• Activity based probes for proteases: applications to biomarker discovery, molecular imaging and drug screening. Fonovi? M,  Bogyo M.  Curr Pharm Des.  2007; 13 (3): 253-61
• Ubiquitin-like modifiers and their deconjugating enzymes in medically important parasitic protozoa. Ponder EL,  Bogyo M.  Eukaryot Cell.  2007; 6 (11): 1943-52
• Finding the needles in the haystack: mapping constitutive proteolytic events in vivo. Bogyo M,  Biochem J.  2007; 407 (1): e1-2
• A mild chemically cleavable linker system for functional proteomic applications. Verhelst SH,  Fonovi? M, Bogyo M.  Angew Chem Int Ed Engl.  2007; 46 (8): 1284-6
• Specificity of aza-peptide electrophile activity-based probes of caspases. Sexton KB,  Kato D, Berger AB, Fonovic M, Verhelst SH, Bogyo M.  Cell Death Differ.  2007; 14 (4): 727-32
• Design of cell-permeable, fluorescent activity-based probes for the lysosomal cysteine protease asparaginyl endopeptidase (AEP)/legumain. Sexton KB,  Witte MD, Blum G, Bogyo M.  Bioorg Med Chem Lett.  2007; 17 (3): 649-53
• Influenza A virus elevates active cathepsin B in primary murine DC. Burster T,  Giffon T, Dahl ME, Björck P, Bogyo M, Weber E, Mahmood K, Lewis DB, Mellins ED.  Int Immunol.  2007; 19 (5): 645-55
• Tagging and detection strategies for activity-based proteomics. Sadaghiani AM,  Verhelst SH, Bogyo M.  Curr Opin Chem Biol.  2007; 11 (1): 20-8
• Solid-phase methods for the preparation of epoxysuccinate-based inhibitors of cysteine proteases. Sadaghiani AM,  Verhelst SH, Bogyo M.  J Comb Chem.  2006 Nov-Dec; 8 (6): 802-4
• Commonly used caspase inhibitors designed based on substrate specificity profiles lack selectivity. Berger AB,  Sexton KB, Bogyo M.  Cell Res.  2006; 16 (12): 961-3
• Novel aza peptide inhibitors and active-site probes of papain-family cysteine proteases. Verhelst SH,  Witte MD, Arastu-Kapur S, Fonovic M, Bogyo M.  Chembiochem.  2006; 7 (6): 943-50
• Metalloproteases see the light. Bogyo M,  Nat Chem Biol.  2006; 2 (5): 229-30
• A general solid phase method for the preparation of diverse azapeptide probes directed against cysteine proteases. Kato D,  Verhelst SH, Sexton KB, Bogyo M.  Org Lett.  2005; 7 (25): 5649-52
• Screening for selective small molecule inhibitors of the proteasome using activity-based probes. Bogyo M,  Methods Enzymol.  2005; 399 609-22
• Proteomics meets microbiology: technical advances in the global mapping of protein expression and function. Phillips CI,  Bogyo M.  Cell Microbiol.  2005; 7 (8): 1061-76
• Solid-phase synthesis of double-headed epoxysuccinyl activity-based probes for selective targeting of papain family cysteine proteases. Verhelst SH,  Bogyo M.  Chembiochem.  2005; 6 (5): 824-7
• Chemical proteomics applied to target identification and drug discovery. Verhelst SH,  Bogyo M.  Biotechniques.  2005; 38 (2): 175-7
• Activity-based protein profiling: applications to biomarker discovery, in vivo imaging and drug discovery. Berger AB,  Vitorino PM, Bogyo M.  Am J Pharmacogenomics.  2004; 4 (6): 371-81
• Activity profiling of papain-like cysteine proteases in plants. van der Hoorn RA,  Leeuwenburgh MA, Bogyo M, Joosten MH, Peck SC.  Plant Physiol.  2004; 135 (3): 1170-8
• Applications for chemical probes of proteolytic activity. Bogyo M,  Baruch A, Jeffery DA, Greenbaum D, Borodovsky A, Ovaa H, Kessler B.  Curr Protoc Protein Sci.  2004; Chapter 21 Unit 21.17
• Growth phase-dependent production of a cell wall-associated elastinolytic cysteine proteinase by Staphylococcus epidermidis. Oleksy A,  Golonka E, Ba?bu?a A, Szmyd G, Moon J, Kubica M, Greenbaum D, Bogyo M, Foster TJ, Travis J, Potempa J.  Biol Chem.  2004; 385 (6): 525-35
• Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway for the biosynthesis of peptide neurotransmitters and hormones. Hook V,  Yasothornsrikul S, Greenbaum D, Medzihradszky KF, Troutner K, Toneff T, Bundey R, Logrinova A, Reinheckel T, Peters C, Bogyo M.  Biol Chem.  2004; 385 (6): 473-80
• Targeted disruption of Plasmodium falciparum cysteine protease, falcipain 1, reduces oocyst production, not erythrocytic stage growth. Eksi S,  Czesny B, Greenbaum DC, Bogyo M, Williamson KC.  Mol Microbiol.  2004; 53 (1): 243-50
• Cathepsin V, a novel and potent elastolytic activity expressed in activated macrophages. Yasuda Y,  Li Z, Greenbaum D, Bogyo M, Weber E, Brömme D.  J Biol Chem.  2004; 279 (35): 36761-70
• A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor. Goulet B,  Baruch A, Moon NS, Poirier M, Sansregret LL, Erickson A, Bogyo M, Nepveu A.  Mol Cell.  2004; 14 (2): 207-19
• Enzyme activity--it's all about image. Baruch A,  Jeffery DA, Bogyo M.  Trends Cell Biol.  2004; 14 (1): 29-35
• O-sulfonation of serine and threonine: mass spectrometric detection and characterization of a new posttranslational modification in diverse proteins throughout the eukaryotes. Medzihradszky KF,  Darula Z, Perlson E, Fainzilber M, Chalkley RJ, Ball H, Greenbaum D, Bogyo M, Tyson DR, Bradshaw RA, Burlingame AL.  Mol Cell Proteomics.  2004; 3 (5): 429-40
• Regulation of collagenase activities of human cathepsins by glycosaminoglycans. Li Z,  Yasuda Y, Li W, Bogyo M, Katz N, Gordon RE, Fields GB, Brömme D.  J Biol Chem.  2004; 279 (7): 5470-9
• Biochemical analysis of the 20 S proteasome of Trypanosoma brucei. Wang CC,  Bozdech Z, Liu CL, Shipway A, Backes BJ, Harris JL, Bogyo M.  J Biol Chem.  2003; 278 (18): 15800-8
• Inhibition of papain-like cysteine proteases and legumain by caspase-specific inhibitors: when reaction mechanism is more important than specificity. Rozman-Pungercar J,  Kopitar-Jerala N, Bogyo M, Turk D, Vasiljeva O, Stefe I, Vandenabeele P, Brömme D, Puizdar V, Fonovi? M, Trstenjak-Prebanda M, Dolenc I, Turk V, Turk B.  Cell Death Differ.  2003; 10 (8): 881-8
• Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter. Yasothornsrikul S,  Greenbaum D, Medzihradszky KF, Toneff T, Bundey R, Miller R, Schilling B, Petermann I, Dehnert J, Logvinova A, Goldsmith P, Neveu JM, Lane WS, Gibson B, Reinheckel T, Peters C, Bogyo M, Hook V.  Proc Natl Acad Sci U S A.  2003; 100 (16): 9590-5
• Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase. Sajid M,  McKerrow JH, Hansell E, Mathieu MA, Lucas KD, Hsieh I, Greenbaum D, Bogyo M, Salter JP, Lim KC, Franklin C, Kim JH, Caffrey CR.  Mol Biochem Parasitol.  2003; 131 (1): 65-75
• Chemical proteomics and its application to drug discovery. Jeffery DA,  Bogyo M.  Curr Opin Biotechnol.  2003; 14 (1): 87-95
• Sequential autolytic processing activates the zymogen of Arg-gingipain. Mikolajczyk J,  Boatright KM, Stennicke HR, Nazif T, Potempa J, Bogyo M, Salvesen GS.  J Biol Chem.  2003; 278 (12): 10458-64
• Pathways accessory to proteasomal proteolysis are less efficient in major histocompatibility complex class I antigen production. Kessler B,  Hong X, Petrovic J, Borodovsky A, Dantuma NP, Bogyo M, Overkleeft HS, Ploegh H, Glas R.  J Biol Chem.  2003; 278 (12): 10013-21
• Substrate specificity of schistosome versus human legumain determined by P1-P3 peptide libraries. Mathieu MA,  Bogyo M, Caffrey CR, Choe Y, Lee J, Chapman H, Sajid M, Craik CS, McKerrow JH.  Mol Biochem Parasitol.  2002; 121 (1): 99-105
• Probing structural determinants distal to the site of hydrolysis that control substrate specificity of the 20S proteasome. Groll M,  Nazif T, Huber R, Bogyo M.  Chem Biol.  2002; 9 (5): 655-62
• Proteasome inhibitors: complex tools for a complex enzyme. Bogyo M,  Wang EW.  Curr Top Microbiol Immunol.  2002; 268 185-208
• Small molecule affinity fingerprinting. A tool for enzyme family subclassification, target identification, and inhibitor design. Greenbaum DC,  Arnold WD, Lu F, Hayrapetian L, Baruch A, Krumrine J, Toba S, Chehade K, Brömme D, Kuntz ID, Bogyo M.  Chem Biol.  2002; 9 (10): 1085-94
• Chemical approaches for functionally probing the proteome. Greenbaum D,  Baruch A, Hayrapetian L, Darula Z, Burlingame A, Medzihradszky KF, Bogyo M.  Mol Cell Proteomics.  2002; 1 (1): 60-8
• Lysine 188 substitutions convert the pattern of proteasome activation by REGgamma to that of REGs alpha and beta. Li J,  Gao X, Ortega J, Nazif T, Joss L, Bogyo M, Steven AC, Rechsteiner M.  EMBO J.  2001; 20 (13): 3359-69
• Global analysis of proteasomal substrate specificity using positional-scanning libraries of covalent inhibitors. Nazif T,  Bogyo M.  Proc Natl Acad Sci U S A.  2001; 98 (6): 2967-72
• Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense. Caffrey CR,  Hansell E, Lucas KD, Brinen LS, Alvarez Hernandez A, Cheng J, Gwaltney SL, Roush WR, Stierhof YD, Bogyo M, Steverding D, McKerrow JH.  Mol Biochem Parasitol.  2001; 118 (1): 61-73
• Defining a link between gap junction communication, proteolysis, and cataract formation. Baruch A,  Greenbaum D, Levy ET, Nielsen PA, Gilula NB, Kumar NM, Bogyo M.  J Biol Chem.  2001; 276 (31): 28999-9006
• Selective targeting of lysosomal cysteine proteases with radiolabeled electrophilic substrate analogs. Bogyo M,  Verhelst S, Bellingard-Dubouchaud V, Toba S, Greenbaum D.  Chem Biol.  2000; 7 (1): 27-38
• Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools. Greenbaum D,  Medzihradszky KF, Burlingame A, Bogyo M.  Chem Biol.  2000; 7 (8): 569-81
• Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity. Wang EW,  Kessler BM, Borodovsky A, Cravatt BF, Bogyo M, Ploegh HL, Glas R.  Proc Natl Acad Sci U S A.  2000; 97 (18): 9990-5
• Release of signal peptide fragments into the cytosol requires cleavage in the transmembrane region by a protease activity that is specifically blocked by a novel cysteine protease inhibitor. Weihofen A,  Lemberg MK, Ploegh HL, Bogyo M, Martoglio B.  J Biol Chem.  2000; 275 (40): 30951-6
• Identification of a cDNA encoding an active asparaginyl endopeptidase of Schistosoma mansoni and its expression in Pichia pastoris. Caffrey CR,  Mathieu MA, Gaffney AM, Salter JP, Sajid M, Lucas KD, Franklin C, Bogyo M, McKerrow JH.  FEBS Lett.  2000; 466 (2-3): 244-8
• Cysteine protease inhibitors as chemotherapy: lessons from a parasite target. Selzer PM,  Pingel S, Hsieh I, Ugele B, Chan VJ, Engel JC, Bogyo M, Russell DG, Sakanari JA, McKerrow JH.  Proc Natl Acad Sci U S A.  1999; 96 (20): 11015-22
• How an inhibitor of the HIV-I protease modulates proteasome activity. Schmidtke G,  Holzhütter HG, Bogyo M, Kairies N, Groll M, de Giuli R, Emch S, Groettrup M.  J Biol Chem.  1999; 274 (50): 35734-40
• Substrate binding and sequence preference of the proteasome revealed by active-site-directed affinity probes. Bogyo M,  Shin S, McMaster JS, Ploegh HL.  Chem Biol.  1998; 5 (6): 307-20
• Antigen presentation. A protease draws first blood. Bogyo M,  Ploegh HL.  Nature.  1998; 396 (6712): 625, 627
• A proteolytic system that compensates for loss of proteasome function. Glas R,  Bogyo M, McMaster JS, Gaczynska M, Ploegh HL.  Nature.  1998; 392 (6676): 618-22
• Proteasome function is dispensable under normal but not under heat shock conditions in Thermoplasma acidophilum. Ruepp A,  Eckerskorn C, Bogyo M, Baumeister W.  FEBS Lett.  1998; 425 (1): 87-90
• Proteasome inhibitors and antigen presentation. Bogyo M,  Gaczynska M, Ploegh HL.  Biopolymers.  1997; 43 (4): 269-80
• Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Bogyo M,  McMaster JS, Gaczynska M, Tortorella D, Goldberg AL, Ploegh H.  Proc Natl Acad Sci U S A.  1997; 94 (13): 6629-34
• Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Wiertz EJ,  Tortorella D, Bogyo M, Yu J, Mothes W, Jones TR, Rapoport TA, Ploegh HL.  Nature.  1996; 384 (6608): 432-8
• The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Wiertz EJ,  Jones TR, Sun L, Bogyo M, Geuze HJ, Ploegh HL.  Cell.  1996; 84 (5): 769-79