Craig Roy, PhD
Waldemar Von Zedtwitz Professor of Microbial Pathogenesis and of Immunobiology and Director of Biological and Biomedical Sciences (BBS); Vice-Chair, Department of Microbial Pathogenesis
Research & Publications
Biography
News
Research Summary
The focus of our research is to understand the molecular and cellular events that enable microbial pathogens to evade host defense mechanisms. In particular, we are interested in how bacteria that replicate inside mammalian cells create specialized vacuoles that support pathogen replication. We have been using Legionella pneumophila and Coxiella burnetii as model pathogens to study this process. We have been characterizing a type IV secretion system called Dot/Icm that delivers bacterial effector proteins into the eukaryotic host cell cytosol. The goals of this research are to determine the mechanism by which these bacterial effector proteins regulate phagosome maturation, modulate host immunity, and subvert eukaryotic cell functions.
Specialized Terms: Molecular; Cellular; Microbial pathogens; Bacteria; Vesicular transport; Legionella pneumophila; Coxiella burnetii; Macrophages; Protozoan; Proteins
Coauthors
Research Interests
Bacteria; Immune System; Macrophages; Protozoan Proteins; Legionella pneumophila; Coxiella burnetii; Vesicular Transport Proteins
Selected Publications
- Developmental Transitions Coordinate Assembly of the Coxiella burnetii Dot/Icm Type IV Secretion SystemPark D, Steiner S, Shao M, Roy CR, Liu J. Developmental Transitions Coordinate Assembly of the Coxiella burnetii Dot/Icm Type IV Secretion System. Infection And Immunity 2022, 90: e00410-22. PMID: 36190257, PMCID: PMC9584302, DOI: 10.1128/iai.00410-22.
- Cover Image: Coxiella burnetii encodes an LvgA‐related protein important for intracellular replication (Cellular Microbiology 06/2021)Steiner S, Meir A, Roy C. Cover Image: Coxiella burnetii encodes an LvgA‐related protein important for intracellular replication (Cellular Microbiology 06/2021). Cellular Microbiology 2021, 23 DOI: 10.1111/cmi.13351.
- Host cell depletion of tryptophan by IFNγ-induced Indoleamine 2,3-dioxygenase 1 (IDO1) inhibits lysosomal replication of Coxiella burnetiiGanesan S, Roy CR. Host cell depletion of tryptophan by IFNγ-induced Indoleamine 2,3-dioxygenase 1 (IDO1) inhibits lysosomal replication of Coxiella burnetii. PLOS Pathogens 2019, 15: e1007955. PMID: 31461509, PMCID: PMC6736304, DOI: 10.1371/journal.ppat.1007955.
- Analysis of Dot/Icm Type IVB Secretion System Subassemblies by Cryoelectron Tomography Reveals Conformational Changes Induced by DotB BindingPark D, Chetrit D, Hu B, Roy CR, Liu J. Analysis of Dot/Icm Type IVB Secretion System Subassemblies by Cryoelectron Tomography Reveals Conformational Changes Induced by DotB Binding. MBio 2020, 11: e03328-19. PMID: 32071271, PMCID: PMC7029142, DOI: 10.1128/mbio.03328-19.
- A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channelChetrit D, Hu B, Christie PJ, Roy CR, Liu J. A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel. Nature Microbiology 2018, 3: 678-686. PMID: 29784975, PMCID: PMC5970066, DOI: 10.1038/s41564-018-0165-z.
- Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant librariesShames SR, Liu L, Havey JC, Schofield WB, Goodman AL, Roy CR. Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e10446-e10454. PMID: 29133401, PMCID: PMC5715750, DOI: 10.1073/pnas.1708553114.
- The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing MotifsHorenkamp FA, Kauffman KJ, Kohler LJ, Sherwood RK, Krueger KP, Shteyn V, Roy CR, Melia TJ, Reinisch KM. The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs. Developmental Cell 2015, 34: 569-576. PMID: 26343456, PMCID: PMC4594837, DOI: 10.1016/j.devcel.2015.08.010.
- A Screen of Coxiella burnetii Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole BiogenesisNewton HJ, Kohler LJ, McDonough JA, Temoche-Diaz M, Crabill E, Hartland EL, Roy CR. A Screen of Coxiella burnetii Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole Biogenesis. PLOS Pathogens 2014, 10: e1004286. PMID: 25080348, PMCID: PMC4117601, DOI: 10.1371/journal.ppat.1004286.
- The Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Legionella Effector ProteinsHubber A, Arasaki K, Nakatsu F, Hardiman C, Lambright D, De Camilli P, Nagai H, Roy CR. The Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Legionella Effector Proteins. PLOS Pathogens 2014, 10: e1004222. PMID: 24992562, PMCID: PMC4081824, DOI: 10.1371/journal.ppat.1004222.
- AMPylation Is Critical for Rab1 Localization to Vacuoles Containing Legionella pneumophilaHardiman CA, Roy CR. AMPylation Is Critical for Rab1 Localization to Vacuoles Containing Legionella pneumophila. MBio 2014, 5: e01035-13. PMID: 24520063, PMCID: PMC3950522, DOI: 10.1128/mbio.01035-13.
- Pathogen signatures activate a ubiquitination pathway that modulates the function of the metabolic checkpoint kinase mTORIvanov SS, Roy CR. Pathogen signatures activate a ubiquitination pathway that modulates the function of the metabolic checkpoint kinase mTOR. Nature Immunology 2013, 14: 1219-1228. PMID: 24121838, PMCID: PMC3839319, DOI: 10.1038/ni.2740.
- Legionella pneumophila proteins that regulate Rab1 membrane cyclingIngmundson A, Delprato A, Lambright DG, Roy CR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 2007, 450: 365-369. PMID: 17952054, DOI: 10.1038/nature06336.
- Ankyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV EffectorsPan X, Lührmann A, Satoh A, Laskowski-Arce MA, Roy CR. Ankyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors. Science 2008, 320: 1651-1654. PMID: 18566289, PMCID: PMC2514061, DOI: 10.1126/science.1158160.
- Asc and Ipaf Inflammasomes Direct Distinct Pathways for Caspase-1 Activation in Response to Legionella pneumophila▿Case CL, Shin S, Roy CR. Asc and Ipaf Inflammasomes Direct Distinct Pathways for Caspase-1 Activation in Response to Legionella pneumophila▿. Infection And Immunity 2009, 77: 1981-1991. PMID: 19237518, PMCID: PMC2681768, DOI: 10.1128/iai.01382-08.
- Host SNAREs mediate fusion of vacuoles containing Legionella pneumophila with vesicles exiting the endoplasmic reticulumArasaki K, Roy C. Host SNAREs mediate fusion of vacuoles containing Legionella pneumophila with vesicles exiting the endoplasmic reticulum. The FASEB Journal 2009, 23: 867.4-867.4. DOI: 10.1096/fasebj.23.1_supplement.867.4.
- Modulation of Rab GTPase function by a protein phosphocholine transferaseMukherjee S, Liu X, Arasaki K, McDonough J, Galán JE, Roy CR. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature 2011, 477: 103-106. PMID: 21822290, PMCID: PMC3206611, DOI: 10.1038/nature10335.
- The Legionella pneumophila Effector DrrA Is Sufficient to Stimulate SNARE-Dependent Membrane FusionArasaki K, Toomre DK, Roy CR. The Legionella pneumophila Effector DrrA Is Sufficient to Stimulate SNARE-Dependent Membrane Fusion. Cell Host & Microbe 2012, 11: 46-57. PMID: 22264512, PMCID: PMC3266541, DOI: 10.1016/j.chom.2011.11.009.
- The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 DeconjugationChoy A, Dancourt J, Mugo B, O’Connor T, Isberg RR, Melia TJ, Roy CR. The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation. Science 2012, 338: 1072-1076. PMID: 23112293, PMCID: PMC3682818, DOI: 10.1126/science.1227026.
- Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophilaCase CL, Kohler LJ, Lima JB, Strowig T, de Zoete MR, Flavell RA, Zamboni DS, Roy CR. Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1851-1856. PMID: 23307811, PMCID: PMC3562791, DOI: 10.1073/pnas.1211521110.
- The Coxiella burnetii effector EmcB is a deubiquitinase that inhibits RIG-I signalingDuncan-Lowey J, Crabill E, Jarret A, Reed S, Roy C. The Coxiella burnetii effector EmcB is a deubiquitinase that inhibits RIG-I signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2217602120. PMID: 36893270, PMCID: PMC10089202, DOI: 10.1073/pnas.2217602120.
- Syntaxin 11 Contributes to the Interferon-Inducible Restriction of Coxiella burnetii Intracellular InfectionGanesan S, Alvarez N, Steiner S, Fowler K, Corona A, Roy C. Syntaxin 11 Contributes to the Interferon-Inducible Restriction of Coxiella burnetii Intracellular Infection. MBio 2023, 14: e03545-22. PMID: 36728431, PMCID: PMC9972978, DOI: 10.1128/mbio.03545-22.
- Manipulation of Host Cell Organelles by Intracellular PathogensOmotade T, Roy C. Manipulation of Host Cell Organelles by Intracellular Pathogens. 2019, 179-196. DOI: 10.1128/9781683670261.ch13.
- How Legionella diverts host small GTPases: structural and biochemical studiesCherfils J, Folly-Klan M, Alix E, Roy C, Stalder D, Antonny B, Campanacci V. How Legionella diverts host small GTPases: structural and biochemical studies. Acta Crystallographica Section A: Foundations And Advances 2013, 69: s313-s313. DOI: 10.1107/s0108767313097298.
- Structure of the Legionella effector AnkX, an enzyme that diverts the small GTPase Rab1Campanacci V, Mukherjee S, Roy C, Cherfils J. Structure of the Legionella effector AnkX, an enzyme that diverts the small GTPase Rab1. Acta Crystallographica Section A: Foundations And Advances 2013, 69: s68-s68. DOI: 10.1107/s010876731309942x.
- Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector proteinLührmann A, Nogueira CV, Carey KL, Roy CR. Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 18997-19001. PMID: 20944063, PMCID: PMC2973885, DOI: 10.1073/pnas.1004380107.
- Genetics of Mouse Macrophage Resistance to Legionella pneumophilaVance R, Ren T, Zamboni D, Roy C, Dietrich W. Genetics of Mouse Macrophage Resistance to Legionella pneumophila. 2006, 301-306. DOI: 10.1128/9781555815660.ch73.
- NALP3: a key player in caspase-1 activationSutterwala F, Ogura Y, Zamboni D, Roy C, Flavell R. NALP3: a key player in caspase-1 activation. Innate Immunity 2006, 12: 251-256. PMID: 16953978, DOI: 10.1177/09680519060120040701.
- Utilization of Endoplasmic Reticulum Membranes to Establish a Vacuole that Supports Replication of Legionella pneumophilaStein M, Roy C. Utilization of Endoplasmic Reticulum Membranes to Establish a Vacuole that Supports Replication of Legionella pneumophila. 2006, 199-210. DOI: 10.1002/352760880x.ch11.
- Host–microbe interactions: bacteria Host–pathogen interactions: interpreting the dialogueRoy C, Sansonetti P. Host–microbe interactions: bacteria Host–pathogen interactions: interpreting the dialogue. Current Opinion In Microbiology 2004, 7: 1-3. DOI: 10.1016/j.mib.2003.12.014.
- How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane.Tilney L, Harb O, Connelly P, Robinson C, Roy C. How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane. Journal Of Cell Science 2001, 114: 4637-50. PMID: 11792828, DOI: 10.1242/jcs.114.24.4637.
- The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporterNagai H, Roy C. The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter. The EMBO Journal 2001, 20: 5962-5970. PMID: 11689436, PMCID: PMC125688, DOI: 10.1093/emboj/20.21.5962.
- Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growthCoers J, Kagan J, Matthews M, Nagai H, Zuckman D, Roy C. Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth. Molecular Microbiology 2000, 38: 719-736. PMID: 11115108, DOI: 10.1046/j.1365-2958.2000.02176.x.
- Identification and Subcellular Localization of the Legionella pneumophila IcmX Protein: a Factor Essential for Establishment of a Replicative Organelle in Eukaryotic Host CellsMatthews M, Roy C. Identification and Subcellular Localization of the Legionella pneumophila IcmX Protein: a Factor Essential for Establishment of a Replicative Organelle in Eukaryotic Host Cells. Infection And Immunity 2000, 68: 3971-3982. PMID: 10858211, PMCID: PMC101675, DOI: 10.1128/iai.68.7.3971-3982.2000.
- Exploitation of macrophages as a replication niche by Legionella pneumophila: ResponseRoy C, Coers J. Exploitation of macrophages as a replication niche by Legionella pneumophila: Response. Trends In Microbiology 2000, 8: 49-50. PMID: 10664593, DOI: 10.1016/s0966-842x(99)01673-x.
- Modulation of phagosome biogenesis by Legionella pneumophila creates an organelle permissive for intracellular growthCoers J, Monahan C, Roy C. Modulation of phagosome biogenesis by Legionella pneumophila creates an organelle permissive for intracellular growth. Nature Cell Biology 1999, 1: 451-453. PMID: 10559990, DOI: 10.1038/15687.
- Pore‐forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growthZuckman D, Hung J, Roy C. Pore‐forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth. Molecular Microbiology 1999, 32: 990-1001. PMID: 10361301, DOI: 10.1046/j.1365-2958.1999.01410.x.
- Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptakeRoy C, Berger K, Isberg R. Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptake. Molecular Microbiology 1998, 28: 663-674. PMID: 9632267, DOI: 10.1046/j.1365-2958.1998.00841.x.
- Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages.Roy C, Isberg R. Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages. Infection And Immunity 1997, 65: 571-8. PMID: 9009315, PMCID: PMC176098, DOI: 10.1128/iai.65.2.571-578.1997.
- Use of Salt to Isolate Legionella pneumophila Mutants Unable to Replicate in MacrophagesVOGEL J, ROY C, ISBERG R. Use of Salt to Isolate Legionella pneumophila Mutants Unable to Replicate in Macrophages. Annals Of The New York Academy Of Sciences 1996, 797: 271-272. PMID: 8993377, DOI: 10.1111/j.1749-6632.1996.tb52975.x.
- Legionella pneumophila: factors involved in the route and response to an intracellular niche.Isberg R, Rankin S, Roy C, Swanson M, Berger K. Legionella pneumophila: factors involved in the route and response to an intracellular niche. Infectious Agents And Disease 1993, 2: 220-3. PMID: 8173798.