Featured Publications
Intestinal tuft cell immune privilege enables norovirus persistence
Strine M, Fagerberg E, Darcy P, Barrón G, Filler R, Alfajaro M, D'Angelo-Gavrish N, Wang F, Graziano V, Menasché B, Damo M, Wang Y, Howitt M, Lee S, Joshi N, Mucida D, Wilen C. Intestinal tuft cell immune privilege enables norovirus persistence. Science Immunology 2024, 9: eadi7038. PMID: 38517952, DOI: 10.1126/sciimmunol.adi7038.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsIntestinal tuft cellsT cellsTufted cellsViral persistenceSite of viral persistenceChemosensory epithelial cellsNormal antigen presentationImmune-privileged nicheIntestinal stem cellsMemory phenotypeImmune privilegeImmune escapeReporter miceAntigen presentationChronic infectionCytotoxic capacityEpithelial cellsNorovirus infectionStem cellsCell interactionsInfectionCell survivalEnteric microbesCellsDYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner
Strine M, Cai W, Wei J, Alfajaro M, Filler R, Biering S, Sarnik S, Chow R, Patil A, Cervantes K, Collings C, DeWeirdt P, Hanna R, Schofield K, Hulme C, Konermann S, Doench J, Hsu P, Kadoch C, Yan Q, Wilen C. DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner. PLOS Biology 2023, 21: e3002097. PMID: 37310920, PMCID: PMC10263356, DOI: 10.1371/journal.pbio.3002097.Peer-Reviewed Original ResearchConceptsGenome-wide CRISPR/Cas9 screenCRISPR/Cas9 screenPathogenic human coronavirusesKinase-independent mannerRegulated kinase 1AProviral host factorNovel drug targetsMultiple cell typesDNA accessibilityHost factorsKinase functionHuman coronavirusesHost genesDistal enhancerNovel regulatorCas9 screenKinase 1AGene expressionNeuronal developmentDYRK1ADrug targetsDiverse coronavirusesProviral activityCell typesSevere acute respiratory syndrome coronavirus 2Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity
Strine M, Alfajaro M, Graziano V, Song J, Hsieh L, Hill R, Guo J, VanDussen K, Orchard R, Baldridge M, Lee S, Wilen C. Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity. Cell Reports 2022, 41: 111593. PMID: 36351394, PMCID: PMC9662704, DOI: 10.1016/j.celrep.2022.111593.Peer-Reviewed Original ResearchTuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces
Strine MS, Wilen CB. Tuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces. PLOS Pathogens 2022, 18: e1010318. PMID: 35271673, PMCID: PMC8912186, DOI: 10.1371/journal.ppat.1010318.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInterkingdom interactionsTuft cellsCell biologyImmune responseMicrobial activationMicrobial sensingCell abundanceMucosal barrier surfacesAntiviral adaptive immune responsesType 2 immune responsesCell heterogeneityExquisite specificityMucosal barrier integrityAdaptive immune responsesMurine norovirusHuman healthKey orchestratorsMicrobial infectionsPathogenic bacteriaBroad intraFlavivirus replicationKey mediatorContext of coinfectionTissue repairImmune evasion
2024
Human Milk Supports Robust Intestinal Organoid Growth, Differentiation, and Homeostatic Cytokine Production
Smith L, Santiago E, Eke C, Gu W, Wang W, Llivichuzhca-Loja D, Kehoe T, St Denis K, Strine M, Taylor S, Tseng G, Konnikova L. Human Milk Supports Robust Intestinal Organoid Growth, Differentiation, and Homeostatic Cytokine Production. Gastro Hep Advances 2024, 3: 1030-1042. PMCID: PMC11550179, DOI: 10.1016/j.gastha.2024.07.007.Peer-Reviewed Original ResearchHuman milk supplementationTNF-related apoptosis inducing ligandDonor human milkLevels of leukemia inhibitory factorNecrotizing enterocolitisCytokine productionInflammatory immune signaturesComplications of prematurityHuman milkChromogranin A stainingSevere gastrointestinal complicationsMilk supplementationCell cycle-promoting genesIntestinal organoidsApoptosis inducing ligandIntestinal epithelial proliferationIntestinal epithelial growthGrowth factor analysisCleaved caspase 3Preterm infantsGestational ageLeukemia inhibitory factorImmune signaturesImmune landscapeHydrolyzed formula
2023
Bacillus subtilis Phages Related to SIOphi from Desert Soils of the Southwest United States
Magness L, Delesalle V, Vill A, Strine M, Chaudhry B, Lichty K, Guffey A, DeCurzio J, Krukonis G. Bacillus subtilis Phages Related to SIOphi from Desert Soils of the Southwest United States. PHAGE 2023, 4: 165-172. DOI: 10.1089/phage.2023.0021.Peer-Reviewed Original ResearchPutative protein coding genesDouble-stranded DNA genomeBacillus subtilis phagePhage host rangeLow GC contentProtein coding genesDiversity of phagesAmino acid similarityPhage clusterPhage evolutionPhage genomeGC contentUnique genesBacillus phagesCoding genesDNA genomeReplication genesModel organismsPhageHost rangeMicrobial dynamicsGenetic differencesGenomeGenesDesert soilsComparative Genomics of Bacillus subtilis Phages Related to phiNIT1 from Desert Soils of the Southwest United States
Vill A, Delesalle V, Magness L, Chaudhry B, Lichty K, Strine M, Guffey A, DeCurzio J, Krukonis G. Comparative Genomics of Bacillus subtilis Phages Related to phiNIT1 from Desert Soils of the Southwest United States. PHAGE 2023, 4: 173-180. DOI: 10.1089/phage.2023.0027.Peer-Reviewed Original ResearchGenomic structureBacillus phagesBacillus subtilis phageGram-positive bacteriumPathogenic Bacillus speciesDiverse genomesIntergenic regionSequence similarityGenetic diversityRepeat sequencesProtein familyRepresentative phagesPhageB. subtilisBacillus subtilisHost rangeBacillus speciesGenomeVirion structureCapsid structureDesert soilsTail lengthSequenceMyovirusesLysis assayA Novel Subcluster of Closely Related Bacillus Phages with Distinct Tail Fiber/Lysin Gene Combinations
Loney R, Delesalle V, Chaudry B, Czerpak M, Guffey A, Goubet-McCall L, McCarty M, Strine M, Tanke N, Vill A, Krukonis G. A Novel Subcluster of Closely Related Bacillus Phages with Distinct Tail Fiber/Lysin Gene Combinations. Viruses 2023, 15: 2267. PMID: 38005943, PMCID: PMC10674732, DOI: 10.3390/v15112267.Peer-Reviewed Original ResearchMurine Norovirus: Additional Protocols for Basic and Antiviral Studies
Wobus C, Peiper A, McSweeney A, Young V, Chaika M, Lane M, Lingemann M, Deerain J, Strine M, Alfajaro M, Helm E, Karst S, Mackenzie J, Taube S, Ward V, Wilen C. Murine Norovirus: Additional Protocols for Basic and Antiviral Studies. Current Protocols 2023, 3: e828. PMID: 37478303, PMCID: PMC10375541, DOI: 10.1002/cpz1.828.Peer-Reviewed Original ResearchThe KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression
Wei J, Alfajaro M, Cai W, Graziano V, Strine M, Filler R, Biering S, Sarnik S, Patel S, Menasche B, Compton S, Konermann S, Hsu P, Orchard R, Yan Q, Wilen C. The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression. PLOS Pathogens 2023, 19: e1011351. PMID: 37410700, PMCID: PMC10325096, DOI: 10.1371/journal.ppat.1011351.Peer-Reviewed Original ResearchConceptsMouse hepatitis virusReceptor expressionTherapeutic targetMERS-CoVMajor SARS-CoV-2 variantsPrimary human airwaySARS-CoV-2 variantsNovel therapeutic targetViral receptor expressionSARS-CoV-2Histone methyltransferase KMT2DIntestinal epithelial cellsCoronavirus SusceptibilityDiverse coronavirusesHistone demethylase KDM6ADPP4 expressionCoronavirus receptorsHost determinantsHepatitis virusHuman airwaysSARS-CoVSmall molecule inhibitionViral entryPotential drug targetsViral receptorsSystematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq
Patel S, Sexton A, Strine M, Wilen C, Simon M, Pyle A. Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq. Nature Communications 2023, 14: 3426. PMID: 37296103, PMCID: PMC10255950, DOI: 10.1038/s41467-023-38623-1.Peer-Reviewed Original ResearchGame over for RSV?
Strine M, Wilen C. Game over for RSV? Science Immunology 2023, 8: eadi8764. PMID: 37276355, PMCID: PMC11528347, DOI: 10.1126/sciimmunol.adi8764.Commentaries, Editorials and LettersPharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Wei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.Peer-Reviewed Original ResearchConceptsMSWI/SNF complexesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionHost-directed therapeutic targetSyndrome coronavirus 2 infectionSARS-CoV-2 infectionSWItch/Sucrose Non-Fermentable (SWI/SNF) chromatinSARS-CoV-2 susceptibilityNon-fermentable (SWI/SNF) chromatinCoronavirus 2 infectionEnzyme 2 (ACE2) expressionSARS-CoV-2 variantsHuman cell typesPrimary human cell typesAirway epithelial cellsDrug-resistant variantsNew drug targetsChromatin accessibilitySNF complexACE2 locusACE2 expressionFactor complexHost determinantsTherapeutic targetConfer resistance
2022
Introduction: Antimicrobial Resistance
Vanderwall M, Strine M. Introduction: Antimicrobial Resistance. The Yale Journal Of Biology And Medicine 2022, 95: 405-406. PMCID: PMC9765332.Commentaries, Editorials and LettersPlasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein
Lapidus S, Liu F, Casanovas-Massana A, Dai Y, Huck J, Lucas C, Klein J, Filler R, Strine M, Sy M, Deme A, Badiane A, Dieye B, Ndiaye I, Diedhiou Y, Mbaye A, Diagne C, Vigan-Womas I, Mbengue A, Sadio B, Diagne M, Moore A, Mangou K, Diallo F, Sene S, Pouye M, Faye R, Diouf B, Nery N, Costa F, Reis M, Muenker M, Hodson D, Mbarga Y, Katz B, Andrews J, Campbell M, Srivathsan A, Kamath K, Baum-Jones E, Faye O, Sall A, Vélez J, Cappello M, Wilson M, Ben-Mamoun C, Tedder R, McClure M, Cherepanov P, Somé F, Dabiré R, Moukoko C, Ouédraogo J, Boum Y, Shon J, Ndiaye D, Wisnewski A, Parikh S, Iwasaki A, Wilen C, Ko A, Ring A, Bei A. Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein. Scientific Reports 2022, 12: 22175. PMID: 36550362, PMCID: PMC9778468, DOI: 10.1038/s41598-022-26709-7.Peer-Reviewed Original ResearchConceptsCross-reactive antibodiesSARS-CoV-2Positive SARS-CoV-2 antibody resultsPositive SARS-CoV-2 antibodiesSARS-CoV-2 reactivitySARS-CoV-2 antibodiesAcute malaria infectionSpike proteinAntibody test resultsPre-pandemic samplesMalaria-endemic countriesPopulation-level immunityMalaria-endemic regionsSpike S1 subunitNon-endemic countriesSARS-CoV-2 spike proteinSARS-CoV-2 proteinsPopulation-level exposureCOVID-19 transmissionMalaria exposureFalse-positive resultsMalaria infectionDisease burdenPlasmodium infectionAntibody resultsComparative Genomics of Six Lytic Bacillus subtilis Phages from the Southwest United States
Vill A, Delesalle V, Tomko B, Lichty K, Strine M, Guffey A, Burton E, Tanke N, Krukonis G. Comparative Genomics of Six Lytic Bacillus subtilis Phages from the Southwest United States. PHAGE 2022, 3: 171-178. PMID: 36793550, PMCID: PMC9917325, DOI: 10.1089/phage.2022.0030.Peer-Reviewed Original ResearchPutative protein coding genesDouble-stranded DNA genomeLoci encoding proteinsLow GC contentProtein coding genesDiversity of phagesAmino acid similarityPhage evolutionGC contentSmall genesGenomic mosaicismCoding genesDNA genomeEncode proteinsProtein foldingModel organismsPhageMicrobial dynamicsGenomeGenesProteinSiphovirusIndelsGenBankNucleotideGenome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection
Biering SB, Sarnik SA, Wang E, Zengel JR, Leist SR, Schäfer A, Sathyan V, Hawkins P, Okuda K, Tau C, Jangid AR, Duffy CV, Wei J, Gilmore RC, Alfajaro MM, Strine MS, Nguyenla X, Van Dis E, Catamura C, Yamashiro LH, Belk JA, Begeman A, Stark JC, Shon DJ, Fox DM, Ezzatpour S, Huang E, Olegario N, Rustagi A, Volmer AS, Livraghi-Butrico A, Wehri E, Behringer RR, Cheon DJ, Schaletzky J, Aguilar HC, Puschnik AS, Button B, Pinsky BA, Blish CA, Baric RS, O’Neal W, Bertozzi CR, Wilen CB, Boucher RC, Carette JE, Stanley SA, Harris E, Konermann S, Hsu PD. Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection. Nature Genetics 2022, 54: 1078-1089. PMID: 35879412, PMCID: PMC9355872, DOI: 10.1038/s41588-022-01131-x.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionHost factorsSARS-CoV-2 entry factors ACE2SARS-CoV-2-host interactionsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Diverse respiratory virusesMild respiratory illnessRespiratory distress syndromeSARS-CoV-2 host factorsHost-directed therapeuticsSyndrome coronavirus 2Coronavirus disease 2019Human lung epithelial cellsRange of symptomsHost defense mechanismsLung epithelial cellsGenome-wide CRISPR knockoutDistress syndromeRespiratory virusesRespiratory illnessCoronavirus 2Cell cycle regulationHigh molecular weight glycoproteinsOmicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2
Fang Z, Peng L, Filler R, Suzuki K, McNamara A, Lin Q, Renauer PA, Yang L, Menasche B, Sanchez A, Ren P, Xiong Q, Strine M, Clark P, Lin C, Ko AI, Grubaugh ND, Wilen CB, Chen S. Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2. Nature Communications 2022, 13: 3250. PMID: 35668119, PMCID: PMC9169595, DOI: 10.1038/s41467-022-30878-4.Peer-Reviewed Original ResearchConceptsHeterologous boosterSARS-CoV-2Antibody responseMRNA vaccinesMRNA vaccinationDelta variantOmicron variantType of vaccinationStrong antibody responseMRNA vaccine candidatesVaccine candidatesNeutralization potencyImmune evasionSARS-CoV.Two weeksComparable titersVaccinationVaccineTiters 10MiceOmicronWeeksWA-1LNP-mRNABooster
2021
Stability of SARS-CoV-2 RNA in Nonsupplemented Saliva - Volume 27, Number 4—April 2021 - Emerging Infectious Diseases journal - CDC
Ott IM, Strine MS, Watkins AE, Boot M, Kalinich CC, Harden CA, Vogels CBF, Casanovas-Massana A, Moore AJ, Muenker MC, Nakahata M, Tokuyama M, Nelson A, Fournier J, Bermejo S, Campbell M, Datta R, Dela Cruz CS, Farhadian SF, Ko AI, Iwasaki A, Grubaugh ND, Wilen CB, Wyllie AL, . Stability of SARS-CoV-2 RNA in Nonsupplemented Saliva - Volume 27, Number 4—April 2021 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases 2021, 27: 1146-1150. PMID: 33754989, PMCID: PMC8007305, DOI: 10.3201/eid2704.204199.Peer-Reviewed Original ResearchCD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus
Graziano VR, Alfajaro MM, Schmitz CO, Filler RB, Strine MS, Wei J, Hsieh LL, Baldridge MT, Nice TJ, Lee S, Orchard RC, Wilen CB. CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus. Journal Of Virology 2021, 95: 10.1128/jvi.01652-20. PMID: 33177207, PMCID: PMC7925115, DOI: 10.1128/jvi.01652-20.Peer-Reviewed Original ResearchConceptsConditional knockout miceIntestinal epithelial cellsCell tropismKnockout miceTuft cellsDendritic cellsMyelomonocytic cellsB cellsCellular tropismMurine norovirusEpithelial cellsViral RNA levelsInnate immune responseCause of gastroenteritisMNoV infectionCell typesViral loadGastrointestinal infectionsReceptor expressionImmunocompetent humansImmune responseCell type-specific rolesMouse modelIntestinal tissueMNoV