Featured Publications
DYRK1A 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 2
2023
The 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 receptorsPharmacological 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
Plasmodium 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 resultsGenome-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 ResearchComprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms
Huston NC, Wan H, Strine MS, de Cesaris Araujo Tavares R, Wilen CB, Pyle AM. Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms. Molecular Cell 2021, 81: 584-598.e5. PMID: 33444546, PMCID: PMC7775661, DOI: 10.1016/j.molcel.2020.12.041.Peer-Reviewed Original ResearchConceptsRNA structureSecondary structureRNA virusesSARS-CoV-2 RNA genomeNovel regulatory motifsSingle-nucleotide resolutionDownstream functional analysisRNA drug targetsPositive-sense RNA virusesGenome architectureGenomic structureEvolutionary analysisRegulatory motifsSARS-CoV-2 genomeViral life cycleRNA genomeFunctional analysisGenomeDrug targetsPrimer designInfected cellsViral RNADepth structural analysisLife cycleΒ-coronavirus
2020
Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
Wei J, Alfajaro MM, DeWeirdt PC, Hanna RE, Lu-Culligan WJ, Cai WL, Strine MS, Zhang SM, Graziano VR, Schmitz CO, Chen JS, Mankowski MC, Filler RB, Ravindra NG, Gasque V, de Miguel FJ, Patil A, Chen H, Oguntuyo KY, Abriola L, Surovtseva YV, Orchard RC, Lee B, Lindenbach BD, Politi K, van Dijk D, Kadoch C, Simon MD, Yan Q, Doench JG, Wilen CB. Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell 2020, 184: 76-91.e13. PMID: 33147444, PMCID: PMC7574718, DOI: 10.1016/j.cell.2020.10.028.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCoronavirusCoronavirus InfectionsCOVID-19Gene Knockout TechniquesGene Regulatory NetworksGenome-Wide Association StudyHEK293 CellsHMGB1 ProteinHost-Pathogen InteractionsHumansSARS-CoV-2Vero CellsVirus InternalizationConceptsSARS-CoV-2 infectionSARS-CoV-2Vesicular stomatitis virusGenome-wide CRISPR screenSWI/SNF chromatinSARS-CoV-2 host factorsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionTherapeutic targetHost factorsCoronavirus disease 2019 (COVID-19) pathogenesisSyndrome coronavirus 2 infectionCRISPR screensHost genesGene productsMiddle East respiratory syndrome CoVCoronavirus 2 infectionGenetic hitsHuman cellsSARS-CoV-2 spikeNovel therapeutic targetPotential therapeutic targetVero E6 cellsSARS-CoV-1Small molecule antagonists