Mia Madel Alfajaro, DVM, PhD, MS
Associate Research ScientistAbout
Research
Publications
2024
SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity
Peña-Hernández M, Alfajaro M, Filler R, Moriyama M, Keeler E, Ranglin Z, Kong Y, Mao T, Menasche B, Mankowski M, Zhao Z, Vogels C, Hahn A, Kalinich C, Zhang S, Huston N, Wan H, Araujo-Tavares R, Lindenbach B, Homer R, Pyle A, Martinez D, Grubaugh N, Israelow B, Iwasaki A, Wilen C. SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity. Nature Microbiology 2024, 9: 2038-2050. PMID: 39075235, DOI: 10.1038/s41564-024-01765-z.Peer-Reviewed Original ResearchBat coronavirusesRelatives of SARS-CoV-2Upper airwayUpper airways of miceEpithelial cellsHuman nasal epithelial cellsAirways of miceMajor histocompatibility complex class I.SARS-CoV-2Nasal epithelial cellsHistocompatibility complex class I.Human bronchial epithelial cellsGenetic similarityBronchial epithelial cellsInnate immune restrictionCoronavirus replicationFunctional characterizationMolecular cloningReduced pathogenesisImpaired replicationBat virusCoronavirus pathogenesisPandemic potentialHigh-risk familiesImmune restrictionIntestinal 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, PMCID: PMC11555782, 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 microbesCellsHuman 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
2023
Pharmacological 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
Tuft-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 ResearchGenome-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 glycoproteinsHigh-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19Patients
2021
Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting
Sun Y, Abriola L, Niederer RO, Pedersen SF, Alfajaro MM, Silva Monteiro V, Wilen CB, Ho YC, Gilbert WV, Surovtseva YV, Lindenbach BD, Guo JU. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2023051118. PMID: 34185680, PMCID: PMC8256030, DOI: 10.1073/pnas.2023051118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 replicationSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Vero E6 cellsHigh-throughput compound screenOpen reading frame 1bEffective antiviral strategiesCoronavirus 2E6 cellsAntiviral strategiesViral gene expressionCompound screenFluoroquinolone antibacterialsFrame 1bGene expressionSingle-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replicationDiscovery 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