2024
Human iPSC-Based Model of COPD to Investigate Disease Mechanisms, Predict SARS-COV-2 Outcome, and Test Preventive Immunotherapy
Dagher R, Moldobaeva A, Gubbins E, Clark S, Alfajaro M, Wilen C, Hawkins F, Qu X, Chiang C, Li Y, Clarke L, Ikeda Y, Brown C, Kolbeck R, Ma Q, Rojas M, Koff J, Ghaedi M. Human iPSC-Based Model of COPD to Investigate Disease Mechanisms, Predict SARS-COV-2 Outcome, and Test Preventive Immunotherapy. Stem Cells 2024, 42: 230-250. PMID: 38183264, DOI: 10.1093/stmcls/sxad094.Peer-Reviewed Original ResearchSARS-CoV-2 infectionAlveolar nicheSARS-CoV-2 outcomesAberrant inflammatory responseModels of COPDDisease-specific mechanismsInflammation/Preventive immunotherapyChronic inflammationEpithelial damageInflammatory responseLung tissueCOPDNovel therapeuticsEpithelial-mesenchymal interactionsMitochondrial dysfunctionInfectionDisease mechanismsHuman iPSCCell deathFibroblast modelSingle-cell levelRepair mechanismsIPSCsImmunotherapy
2022
Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction.
Peng X, Kim J, Gupta G, Agaronyan K, Mankowski MC, Korde A, Takyar SS, Shin HJ, Habet V, Voth S, Audia JP, Chang D, Liu X, Wang L, Cai Y, Tian X, Ishibe S, Kang MJ, Compton S, Wilen CB, Dela Cruz CS, Sharma L. Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction. The Journal Of Immunology 2022, 209: 1314-1322. PMID: 36165196, PMCID: PMC9523490, DOI: 10.4049/jimmunol.2200198.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Bacterial infectionsMouse modelCoronavirus infectionLysosomal dysfunctionMajor health care challengeLung immune cellsLung tissue damageSecondary bacterial infectionImpair host immunityIL-1β releaseHealth care challengesCell deathPyroptotic cell deathBacterial killing abilityIL-1βBacterial clearanceImmune cellsSecondary infectionHost immunityAlveolar macrophagesTissue damageΒ-coronavirusStructural cellsCare challenges
2021
Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions
Flynn RA, Belk JA, Qi Y, Yasumoto Y, Wei J, Alfajaro MM, Shi Q, Mumbach MR, Limaye A, DeWeirdt PC, Schmitz CO, Parker KR, Woo E, Chang HY, Horvath TL, Carette JE, Bertozzi CR, Wilen CB, Satpathy AT. Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell 2021, 184: 2394-2411.e16. PMID: 33743211, PMCID: PMC7951565, DOI: 10.1016/j.cell.2021.03.012.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 RNASARS-CoV-2Virus-induced cell deathHost protein interactionsRNA-binding proteinActive infectionRNA virusesHost-virus interfaceGlobal mortalityTherapeutic benefitCRISPR screensAntiviral factorsProtein interactionsAntiviral activityViral specificityHost pathwaysFunctional RNA-binding proteinsFunctional connectionsRNA-centric approachesCell deathHost proteinsVirusFunctional interrogationRNAComprehensive catalog
2020
Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection
Urbanek K, Sutherland DM, Orchard RC, Wilen CB, Knowlton JJ, Aravamudhan P, Taylor GM, Virgin HW, Dermody TS. Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection. Journal Of Virology 2020, 95: 10.1128/jvi.01571-20. PMID: 33087464, PMCID: PMC7944449, DOI: 10.1128/jvi.01571-20.Peer-Reviewed Original ResearchConceptsSialic acid expressionMicroglial cellsCell surface expressionReovirus-induced cell deathReovirus infectionSialic acidMurine microglial BV2 cellsReovirus-induced diseaseMember A1Microglial BV2 cellsSurface expressionMurine microglial cellsCell deathReovirus bindingBV2 cellsViral tropismInfectionHost genesLow-level bindingCell surface receptorsHost factorsCell surfaceReceptorsSialic acid synthesisSurface receptors
2016
Discovery of a proteinaceous cellular receptor for a norovirus
Orchard RC, Wilen CB, Doench JG, Baldridge MT, McCune BT, Lee YC, Lee S, Pruett-Miller SM, Nelson CA, Fremont DH, Virgin HW. Discovery of a proteinaceous cellular receptor for a norovirus. Science 2016, 353: 933-936. PMID: 27540007, PMCID: PMC5484048, DOI: 10.1126/science.aaf1220.Peer-Reviewed Original ResearchConceptsProteinaceous receptorsMNoV infectionCellular machineryNoV replicationHuman cellsCell deathSpecies barrierCD300lfSpecies tropismPrimary cellsCellular receptorsCell linesMurine NoVHost factorsReplicationCause of gastroenteritisPrimary determinantNoV infectionReceptorsCellsEctodomainMachineryInfectionCrystal structureResidues