Joseph Bondy-Denomy, PhD
Associate Professor
Microbiology and Immunology
School of Medicine

In the Bondy-Denomy lab, we study CRISPR-Cas bacterial immune systems in an effort to understand their role in antagonizing viruses called bacteriophages. We are very interested in how CRISPR works and the ways that phages inhibit and evade CRISPR-Cas function.

Education & Training

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• PhD Molecular Genetics University of Toronto 11/2014
• BSc Biology, Microbiology University of Waterloo 08/2008

Websites

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• Bondy-Denomy Lab (bondydenomylab.com)

Grants and Projects

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• Uncovering the mechanism and role of a widespread anti-CRISPR-Cas9 protein, NIH, 2018-2023
• Discovering New Roles for CRISPR-Cas in Bacterial Pathogenesis, NIH, 2015-2021

Publications (82)

Top publication keywords:
Viral ProteinsInterspersed Repetitive SequencesProphagesEndonucleasesPseudomonas aeruginosaGene EditingListeriaCRISPR-Associated ProteinsPseudomonas PhagesClustered Regularly Interspaced Short Palindromic RepeatsBacteriaGenetic EngineeringListeria monocytogenesBacteriophagesCRISPR-Cas Systems

• Multi-interface licensing of protein import into a phage nucleus.
  Nature 2025 Kokontis C, Klein TA, Silas S, Bondy-Denomy J
• Exploring the diversity of anti-defense systems across prokaryotes, phages and mobile genetic elements.
  Nucleic acids research 2025 Tesson F, Huiting E, Wei L, Ren J, Johnson M, Planel R, Cury J, Feng Y, Bondy-Denomy J, Bernheim A
• Single phage proteins sequester signals from TIR and cGAS-like enzymes.
  Nature 2024 Li D, Xiao Y, Fedorova I, Xiong W, Wang Y, Liu X, Huiting E, Ren J, Gao Z, Zhao X, Cao X, Zhang Y, Bondy-Denomy J, Feng Y
• Diverse viral cas genes antagonize CRISPR immunity.
  Nature 2024 Katz MA, Sawyer EM, Oriolt L, Kozlova A, Williams MC, Margolis SR, Johnson M, Bondy-Denomy J, Meeske AJ
• AcrIF11 is a potent CRISPR-specific ADP-ribosyltransferase encoded by phage and plasmid.
  bioRxiv : the preprint server for biology 2024 Chen DF, Roe LT, Li Y, Borges AL, Zhang JY, Babbar P, Maji S, Stevens MGV, Correy GJ, Diolaiti ME, Smith DH, Ashworth A, Stroud RM, Kelly MJS, Bondy-Denomy J, Fraser JS

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• Exploring the diversity of anti-defense systems across prokaryotes, phages, and mobile genetic elements.
  bioRxiv : the preprint server for biology 2024 Tesson F, Huiting E, Wei L, Ren J, Johnson M, Planel R, Cury J, Feng Y, Bondy-Denomy J, Bernheim A
• Characterization of a lipid-based jumbo phage compartment as a hub for early phage infection.
  Cell host & microbe 2024 Mozumdar D, Fossati A, Stevenson E, Guan J, Nieweglowska E, Rao S, Agard D, Swaney DL, Bondy-Denomy J
• Anti-CRISPR proteins trigger a burst of CRISPR-Cas9 expression that enhances phage defense.
  Cell reports 2024 Workman RE, Stoltzfus MJ, Keith NC, Euler CW, Bondy-Denomy J, Modell JW
• Phage anti-CBASS protein simultaneously sequesters cyclic trinucleotides and dinucleotides.
  Molecular cell 2023 Cao X, Xiao Y, Huiting E, Cao X, Li D, Ren J, Fedorova I, Wang H, Guan L, Wang Y, Li L, Bondy-Denomy J, Feng Y
• Cas9 degradation in human cells using phage anti-CRISPR proteins.
  PLoS biology 2023 Meacham Z, de Tacca LA, Bondy-Denomy J, Rabuka D, Schelle M
• Identification of an anti-CRISPR protein that inhibits the CRISPR-Cas type I-B system in Clostridioides difficile.
  mSphere 2023 Muzyukina P, Shkaruta A, Guzman NM, Andreani J, Borges AL, Bondy-Denomy J, Maikova A, Semenova E, Severinov K, Soutourina O
• Single phage proteins sequester TIR- and cGAS-generated signaling molecules.
  bioRxiv : the preprint server for biology 2023 Li D, Xiao Y, Xiong W, Fedorova I, Wang Y, Liu X, Huiting E, Ren J, Gao Z, Zhao X, Cao X, Zhang Y, Bondy-Denomy J, Feng Y
• Next-generation proteomics for quantitative Jumbophage-bacteria interaction mapping.
  Nature communications 2023 Fossati A, Mozumdar D, Kokontis C, Mèndez-Moran M, Nieweglowska E, Pelin A, Li Y, Guo B, Krogan NJ, Agard DA, Bondy-Denomy J, Swaney DL
• Core defense hotspots within Pseudomonas aeruginosa are a consistent and rich source of anti-phage defense systems.
  Nucleic acids research 2023 Johnson MC, Laderman E, Huiting E, Zhang C, Davidson A, Bondy-Denomy J
• F-Type Pyocins Are Diverse Noncontractile Phage Tail-Like Weapons for Killing Pseudomonas aeruginosa.
  Journal of bacteriology 2023 Saha S, Ojobor CD, Li ASC, Mackinnon E, North OI, Bondy-Denomy J, Lam JS, Ensminger AW, Maxwell KL, Davidson AR
• Phage anti-CBASS protein simultaneously sequesters cyclic trinucleotides and dinucleotides.
  bioRxiv : the preprint server for biology 2023 Cao X, Xiao Y, Huiting E, Cao X, Li D, Ren J, Guan L, Wang Y, Li L, Bondy-Denomy J, Feng Y
• Defining the expanding mechanisms of phage-mediated activation of bacterial immunity.
  Current opinion in microbiology 2023 Huiting E, Bondy-Denomy J
• Ten Years of Anti-CRISPR Research.
  Journal of molecular biology 2023 Bondy-Denomy J, Maxwell KL, Davidson AR
• Next-generation interaction proteomics for quantitative Jumbophage-bacteria interaction mapping.
  bioRxiv : the preprint server for biology 2023 Fossati A, Mozumdar D, Kokontis C, Mèndez-Moran M, Nieweglowska E, Pelin A, Li Y, Guo B, Krogan NJ, Agard DA, Bondy-Denomy J, Swaney DL
• The ϕPA3 phage nucleus is enclosed by a self-assembling 2D crystalline lattice.
  Nature communications 2023 Nieweglowska ES, Brilot AF, Méndez-Moran M, Kokontis C, Baek M, Li J, Cheng Y, Baker D, Bondy-Denomy J, Agard DA
• Bacteriophages inhibit and evade cGAS-like immune function in bacteria.
  Cell 2023 Huiting E, Cao X, Ren J, Athukoralage JS, Luo Z, Silas S, An N, Carion H, Zhou Y, Fraser JS, Feng Y, Bondy-Denomy J
• Bacteriophage genome engineering with CRISPR-Cas13a.
  Nature microbiology 2022 Guan J, Oromí-Bosch A, Mendoza SD, Karambelkar S, Berry JD, Bondy-Denomy J
• Structural basis of AcrIF24 as an anti-CRISPR protein and transcriptional suppressor.
  Nature chemical biology 2022 Mukherjee IA, Gabel C, Noinaj N, Bondy-Denomy J, Chang L
• CRISPR-Cas12a targeting of ssDNA plays no detectable role in immunity.
  Nucleic acids research 2022 Marino ND, Pinilla-Redondo R, Bondy-Denomy J
• Lack of Cas13a inhibition by anti-CRISPR proteins from Leptotrichia prophages.
  Molecular cell 2022 Johnson MC, Hille LT, Kleinstiver BP, Meeske AJ, Bondy-Denomy J
• A single bacterial enzyme i(NHI)bits phage DNA replication.
  Cell host & microbe 2022 Huiting E, Bondy-Denomy J
• Distinct Subcellular Localization of a Type I CRISPR Complex and the Cas3 Nuclease in Bacteria.
  Journal of bacteriology 2022 Govindarajan S, Borges A, Karambelkar S, Bondy-Denomy J
• Genetic Manipulation of a CAST of Characters in a Microbial Community.
  The CRISPR journal 2022 Mozumdar D, Csörgo B, Bondy-Denomy J
• Publisher Correction: CRISPR inactivation by integration.
  Nature microbiology 2022 Bondy-Denomy J
• CRISPR inactivation by integration.
  Nature microbiology 2021 Bondy-Denomy J
• Positioning Diverse Type IV Structures and Functions Within Class 1 CRISPR-Cas Systems.
  Frontiers in microbiology 2021 Taylor HN, Laderman E, Armbrust M, Hallmark T, Keiser D, Bondy-Denomy J, Jackson RN
• Mobile element warfare via CRISPR and anti-CRISPR in Pseudomonas aeruginosa.
  Nucleic acids research 2021 León LM, Park AE, Borges AL, Zhang JY, Bondy-Denomy J
• Anti-CRISPRs go viral: The infection biology of CRISPR-Cas inhibitors.
  Cell host & microbe 2021 Li Y, Bondy-Denomy J
• A phage-encoded anti-activator inhibits quorum sensing in Pseudomonas aeruginosa.
  Molecular cell 2021 Shah M, Taylor VL, Bona D, Tsao Y, Stanley SY, Pimentel-Elardo SM, McCallum M, Bondy-Denomy J, Howell PL, Nodwell JR, Davidson AR, Moraes TF, Maxwell KL
• Intracellular Organization by Jumbo Bacteriophages.
  Journal of bacteriology 2020 Guan J, Bondy-Denomy J
• Discovery of multiple anti-CRISPRs highlights anti-defense gene clustering in mobile genetic elements.
  Nature communications 2020 Pinilla-Redondo R, Shehreen S, Marino ND, Fagerlund RD, Brown CM, Sørensen SJ, Fineran PC, Bondy-Denomy J
• A compact Cascade-Cas3 system for targeted genome engineering.
  Nature methods 2020 Csörgo B, León LM, Chau-Ly IJ, Vasquez-Rifo A, Berry JD, Mahendra C, Crawford ED, Lewis JD, Bondy-Denomy J
• Machine-learning approach expands the repertoire of anti-CRISPR protein families.
  Nature communications 2020 Gussow AB, Park AE, Borges AL, Shmakov SA, Makarova KS, Wolf YI, Bondy-Denomy J, Koonin EV
• Structures and Strategies of Anti-CRISPR-Mediated Immune Suppression.
  Annual review of microbiology 2020 Wiegand T, Karambelkar S, Bondy-Denomy J, Wiedenheft B
• Author Correction: Broad-spectrum anti-CRISPR proteins facilitate horizontal gene transfer.
  Nature microbiology 2020 Mahendra C, Christie KA, Osuna BA, Pinilla-Redondo R, Kleinstiver BP, Bondy-Denomy J
• Critical Anti-CRISPR Locus Repression by a Bi-functional Cas9 Inhibitor.
  Cell host & microbe 2020 Osuna BA, Karambelkar S, Mahendra C, Sarbach A, Johnson MC, Kilcher S, Bondy-Denomy J
• Listeria Phages Induce Cas9 Degradation to Protect Lysogenic Genomes.
  Cell host & microbe 2020 Osuna BA, Karambelkar S, Mahendra C, Christie KA, Garcia B, Davidson AR, Kleinstiver BP, Kilcher S, Bondy-Denomy J
• Broad-spectrum anti-CRISPR proteins facilitate horizontal gene transfer.
  Nature microbiology 2020 Mahendra C, Christie KA, Osuna BA, Pinilla-Redondo R, Kleinstiver BP, Bondy-Denomy J
• Bacterial alginate regulators and phage homologs repress CRISPR-Cas immunity.
  Nature microbiology 2020 Borges AL, Castro B, Govindarajan S, Solvik T, Escalante V, Bondy-Denomy J
• Anti-CRISPR protein applications: natural brakes for CRISPR-Cas technologies.
  Nature methods 2020 Marino ND, Pinilla-Redondo R, Csörgo B, Bondy-Denomy J
• Author Correction: Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth's biomes.
  Nature microbiology 2020 Roux S, Krupovic M, Daly RA, Borges AL, Nayfach S, Schulz F, Sharrar A, Matheus Carnevali PB, Cheng JF, Ivanova NN, Bondy-Denomy J, Wrighton KC, Woyke T, Visel A, Kyrpides NC, Eloe-Fadrosh EA
• A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases.
  Nature 2019 Mendoza SD, Nieweglowska ES, Govindarajan S, Leon LM, Berry JD, Tiwari A, Chaikeeratisak V, Pogliano J, Agard DA, Bondy-Denomy J
• A Type IV-A CRISPR-Cas System in Pseudomonas aeruginosa Mediates RNA-Guided Plasmid Interference In Vivo.
  The CRISPR journal 2019 Crowley VM, Catching A, Taylor HN, Borges AL, Metcalf J, Bondy-Denomy J, Jackson RN
• Molecular mechanism of azithromycin resistance among typhoidal Salmonella strains in Bangladesh identified through passive pediatric surveillance.
  PLoS neglected tropical diseases 2019 Hooda Y, Sajib MSI, Rahman H, Luby SP, Bondy-Denomy J, Santosham M, Andrews JR, Saha SK, Saha S
• CRISPR-Cas System of a Prevalent Human Gut Bacterium Reveals Hyper-targeting against Phages in a Human Virome Catalog.
  Cell host & microbe 2019 Soto-Perez P, Bisanz JE, Berry JD, Lam KN, Bondy-Denomy J, Turnbaugh PJ
• Anti-CRISPR-Associated Proteins Are Crucial Repressors of Anti-CRISPR Transcription.
  Cell 2019 Stanley SY, Borges AL, Chen KH, Swaney DL, Krogan NJ, Bondy-Denomy J, Davidson AR
• Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth's biomes.
  Nature microbiology 2019 Roux S, Krupovic M, Daly RA, Borges AL, Nayfach S, Schulz F, Sharrar A, Matheus Carnevali PB, Cheng JF, Ivanova NN, Bondy-Denomy J, Wrighton KC, Woyke T, Visel A, Kyrpides NC, Eloe-Fadrosh EA
• Cas13 Helps Bacteria Play Dead when the Enemy Strikes.
  Cell host & microbe 2019 Mendoza SD, Bondy-Denomy J
• Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells.
  Nature communications 2019 Nakamura M, Srinivasan P, Chavez M, Carter MA, Dominguez AA, La Russa M, Lau MB, Abbott TR, Xu X, Zhao D, Gao Y, Kipniss NH, Smolke CD, Bondy-Denomy J, Qi LS
• Temperature-Responsive Competitive Inhibition of CRISPR-Cas9.
  Molecular cell 2018 Jiang F, Liu JJ, Osuna BA, Xu M, Berry JD, Rauch BJ, Nogales E, Bondy-Denomy J, Doudna JA
• Phage Morons Play an Important Role in Pseudomonas aeruginosa Phenotypes.
  Journal of bacteriology 2018 Tsao YF, Taylor VL, Kala S, Bondy-Denomy J, Khan AN, Bona D, Cattoir V, Lory S, Davidson AR, Maxwell KL
• A Unified Resource for Tracking Anti-CRISPR Names.
  The CRISPR journal 2018 Bondy-Denomy J, Davidson AR, Doudna JA, Fineran PC, Maxwell KL, Moineau S, Peng X, Sontheimer EJ, Wiedenheft B
• Discovery of widespread type I and type V CRISPR-Cas inhibitors.
  Science (New York, N.Y.) 2018 Marino ND, Zhang JY, Borges AL, Sousa AA, Leon LM, Rauch BJ, Walton RT, Berry JD, Joung JK, Kleinstiver BP, Bondy-Denomy J
• Bacteriophage Cooperation Suppresses CRISPR-Cas3 and Cas9 Immunity.
  Cell 2018 Borges AL, Zhang JY, Rollins MF, Osuna BA, Wiedenheft B, Bondy-Denomy J
• Protein Inhibitors of CRISPR-Cas9.
  ACS chemical biology 2018 Bondy-Denomy J
• How bacteria control the CRISPR-Cas arsenal.
  Current opinion in microbiology 2017 Leon LM, Mendoza SD, Bondy-Denomy J
• Pseudomonas aeruginosa defends against phages through type IV pilus glycosylation.
  Nature microbiology 2017 Harvey H, Bondy-Denomy J, Marquis H, Sztanko KM, Davidson AR, Burrows LL
• The Discovery, Mechanisms, and Evolutionary Impact of Anti-CRISPRs.
  Annual review of virology 2017 Borges AL, Davidson AR, Bondy-Denomy J
• Disabling Cas9 by an anti-CRISPR DNA mimic.
  Science advances 2017 Shin J, Jiang F, Liu JJ, Bray NL, Rauch BJ, Baik SH, Nogales E, Bondy-Denomy J, Corn JE, Doudna JA
• Cas1 and the Csy complex are opposing regulators of Cas2/3 nuclease activity.
  Proceedings of the National Academy of Sciences of the United States of America 2017 Rollins MF, Chowdhury S, Carter J, Golden SM, Wilkinson RA, Bondy-Denomy J, Lander GC, Wiedenheft B
• Structure Reveals Mechanisms of Viral Suppressors that Intercept a CRISPR RNA-Guided Surveillance Complex.
  Cell 2017 Chowdhury S, Carter J, Rollins MF, Golden SM, Jackson RN, Hoffmann C, Nosaka L, Bondy-Denomy J, Maxwell KL, Davidson AR, Fischer ER, Lander GC, Wiedenheft B
• CRISPR control of virulence in Pseudomonas aeruginosa.
  Cell research 2017 Wiedenheft B, Bondy-Denomy J
• Inhibition of CRISPR-Cas9 with Bacteriophage Proteins.
  Cell 2016 Rauch BJ, Silvis MR, Hultquist JF, Waters CS, McGregor MJ, Krogan NJ, Bondy-Denomy J
• Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system.
  Proceedings of the National Academy of Sciences of the United States of America 2016 Høyland-Kroghsbo NM, Paczkowski J, Mukherjee S, Broniewski J, Westra E, Bondy-Denomy J, Bassler BL
• The solution structure of an anti-CRISPR protein.
  Nature communications 2016 Maxwell KL, Garcia B, Bondy-Denomy J, Bona D, Hidalgo-Reyes Y, Davidson AR
• Prophages mediate defense against phage infection through diverse mechanisms.
  The ISME journal 2016 Bondy-Denomy J, Qian J, Westra ER, Buckling A, Guttman DS, Davidson AR, Maxwell KL
• The diversity-generating benefits of a prokaryotic adaptive immune system.
  Nature 2016 van Houte S, Ekroth AK, Broniewski JM, Chabas H, Ashby B, Bondy-Denomy J, Gandon S, Boots M, Paterson S, Buckling A, Westra ER
• Active and adaptive Legionella CRISPR-Cas reveals a recurrent challenge to the pathogen.
  Cellular microbiology 2016 Rao C, Guyard C, Pelaz C, Wasserscheid J, Bondy-Denomy J, Dewar K, Ensminger AW
• Foreign DNA acquisition by the I-F CRISPR-Cas system requires all components of the interference machinery.
  Nucleic acids research 2015 Vorontsova D, Datsenko KA, Medvedeva S, Bondy-Denomy J, Savitskaya EE, Pougach K, Logacheva M, Wiedenheft B, Davidson AR, Severinov K, Semenova E
• Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins.
  Nature 2015 Bondy-Denomy J, Garcia B, Strum S, Du M, Rollins MF, Hidalgo-Reyes Y, Wiedenheft B, Maxwell KL, Davidson AR
• Parasite Exposure Drives Selective Evolution of Constitutive versus Inducible Defense.
  Current biology : CB 2015 Westra ER, van Houte S, Oyesiku-Blakemore S, Makin B, Broniewski JM, Best A, Bondy-Denomy J, Davidson A, Boots M, Buckling A
• A new group of phage anti-CRISPR genes inhibits the type I-E CRISPR-Cas system of Pseudomonas aeruginosa.
  mBio 2014 Pawluk A, Bondy-Denomy J, Cheung VH, Maxwell KL, Davidson AR
• When a virus is not a parasite: the beneficial effects of prophages on bacterial fitness.
  Journal of microbiology (Seoul, Korea) 2014 Bondy-Denomy J, Davidson AR
• To acquire or resist: the complex biological effects of CRISPR-Cas systems.
  Trends in microbiology 2014 Bondy-Denomy J, Davidson AR
• Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system.
  Nature 2012 Bondy-Denomy J, Pawluk A, Maxwell KL, Davidson AR
• Efficacy of bacteriophage treatment on Pseudomonas aeruginosa biofilms.
  Journal of endodontics 2012 Phee A, Bondy-Denomy J, Kishen A, Basrani B, Azarpazhooh A, Maxwell K
• The CRISPR/Cas adaptive immune system of Pseudomonas aeruginosa mediates resistance to naturally occurring and engineered phages.
  Journal of bacteriology 2012 Cady KC, Bondy-Denomy J, Heussler GE, Davidson AR, O'Toole GA