Craig B. Wilen, MD, PhD
Associate Professor TermDownloadHi-Res Photo
Cards
Appointments
Laboratory Medicine
Primary
Immunobiology
Secondary
Additional Titles
Medical Director, Immune Monitoring Core Facility
Contact Info
Appointments
Laboratory Medicine
Primary
Immunobiology
Secondary
Additional Titles
Medical Director, Immune Monitoring Core Facility
Contact Info
Appointments
Laboratory Medicine
Primary
Immunobiology
Secondary
Additional Titles
Medical Director, Immune Monitoring Core Facility
Contact Info
About
Titles
Associate Professor Term
Medical Director, Immune Monitoring Core Facility
Biography
Dr. Wilen is an Associate Professor in Laboratory Medicine and Immunobiology and is focused on the host-pathogen interactions of RNA viruses including coronavirus and norovirus. Dr. Wilen received his A.B in Biology and Economics at Washington University in St. Louis, his MD and PhD from the University of Pennsylvania. His residency training was in clinical pathology at Barnes-Jewish Hospital in St. Louis, MO. His postdoctoral studies were conducted in the laboratory of Herbert "Skip" Virgin at Washington University School of Medicine where he studied the pathogenesis of norovirus, the leading cause of acute gastroenteritis. Dr. Wilen discovered CD300lf as the first receptor for a norovirus and identified intestinal tuft cells as the physiologic target cell for mouse norovirus infection. Current work in the Wilen lab is focused on identifying mechanisms of immunity and pathogenesis for noroviruses, coronaviruses, and pre-emergent viruses with pandemic potential. The goals of this work are to enable improved risk stratification and to develop improved therapeutics and vaccines to reduce the disease burden from viruses.
Appointments
Laboratory Medicine
Associate Professor on TermPrimaryImmunobiology
Associate Professor on TermSecondary
Other Departments & Organizations
- Center for Infection and Immunity
- Center for RNA Science and Medicine
- Clinical Chemistry Laboratory
- Genomics, Genetics, and Epigenetics
- Human and Translational Immunology Program
- Immune Monitoring Core Facility
- Immunobiology
- Immunology
- Laboratory Medicine
- Microbiology
- Virology Laboratories
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Medicine
Education & Training
- Instructor
- Washington University School of Medicine (2018)
- Resident in Clinical Pathology
- Barnes-Jewish Hospital (2016)
- MD
- University of Pennsylvania, Perelman School of Medicine (2013)
- PhD
- University of Pennsylvania, Perelman School of Medicine (2011)
- AB
- Washington University in St. Louis, Biology and Economics (2006)
Research
Overview
Host-pathogen interaction, viral immunity
Medical Subject Headings (MeSH)
Coronavirus; COVID-19; Immune Evasion; Immune System Diseases; Norovirus; RNA Viruses; Virology
ORCID
0000-0003-2495-9403- View Lab Website
Wilen Lab
Research at a Glance
Yale Co-Authors
Frequent collaborators of Craig B. Wilen's published research.
Publications Timeline
A big-picture view of Craig B. Wilen's research output by year.
Research Interests
Research topics Craig B. Wilen is interested in exploring.
Madison Strine, PhD
Mia Madel Alfajaro, DVM, PhD, MS
Akiko Iwasaki, PhD
Nathan Grubaugh, PhD
Chantal Vogels, PhD
Sidi Chen, PhD
102Publications
11,954Citations
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 ResearchAltmetricConceptsBat 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 restrictionA novel microporous biomaterial vaccine platform for long-lasting antibody mediated immunity against viral infection
Mayer D, Nelson M, Andriyanova D, Filler R, Ökten A, Antao O, Chen J, Scumpia P, Weaver W, Wilen C, Deshayes S, Weinstein J. A novel microporous biomaterial vaccine platform for long-lasting antibody mediated immunity against viral infection. Journal Of Controlled Release 2024, 370: 570-582. PMID: 38734312, DOI: 10.1016/j.jconrel.2024.05.008.Peer-Reviewed Original ResearchCitationsAltmetricConceptsAntigen delivery platformGerminal centersCD4<sup>+</sup> T follicular helper (Tfh) cellsT follicular helper (Tfh) cellsAdaptive immune cell responsesOptimal adaptive immune responsesAnti-receptor binding domain antibodiesInfluenza virus challengeRobust neutralizing antibodiesImmune cell responsesEnhanced neutralizing antibodiesAdaptive immune responsesDelivery platformAntibody mediated immunityLymph nodesVaccine platformNeutralizing antibodiesHumoral immunitySARS-CoV-2 spike proteinSustained release profileTarget antigenImmune responseVirus challengeViral infectionCell responsesIntranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virusIntestinal 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCD8<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 microbesCellsGenome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB–dependent IFITM3 expression
Munir M, Embry A, Doench J, Heaton N, Wilen C, Orchard R. Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB–dependent IFITM3 expression. Journal Of Biological Chemistry 2024, 300: 107153. PMID: 38462163, PMCID: PMC11001640, DOI: 10.1016/j.jbc.2024.107153.Peer-Reviewed Original ResearchCitationsAltmetricConceptsInterferon-induced transmembrane protein 3Influenza A virus infectionCRISPR activation screenGenome-wide CRISPR activation screenIFITM3 expressionResistant to influenza A virus infectionHBO1 complexRegulate transcriptionModify chromatinNF-kB signaling pathwayNF-kBInnate immune systemInfluenza A virusAntiviral genesInteraction pathwaySignaling pathwayInduced expressionActivity screeningImmune landscapeA virusProtein 3Novel nodesExpressionImmune systemInfluenzaHuman 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 ResearchCitationsAltmetricConceptsSARS-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
Survey of white-footed mice (Peromyscus leucopus) in Connecticut, USA reveals low SARS-CoV-2 seroprevalence and infection with divergent betacoronaviruses
Earnest R, Hahn A, Feriancek N, Brandt M, Filler R, Zhao Z, Breban M, Vogels C, Chen N, Koch R, Porzucek A, Sodeinde A, Garbiel A, Keanna C, Litwak H, Stuber H, Cantoni J, Pitzer V, Olarte Castillo X, Goodman L, Wilen C, Linske M, Williams S, Grubaugh N. Survey of white-footed mice (Peromyscus leucopus) in Connecticut, USA reveals low SARS-CoV-2 seroprevalence and infection with divergent betacoronaviruses. Npj Viruses 2023, 1: 10. DOI: 10.1038/s44298-023-00010-4.Peer-Reviewed Original ResearchCitationsAltmetricDifferences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53
Lee J, Menasche B, Mavrikaki M, Uyemura M, Hong S, Kozlova N, Wei J, Alfajaro M, Filler R, Müller A, Saxena T, Posey R, Cheung P, Muranen T, Heng Y, Paulo J, Wilen C, Slack F. Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53. Cell Reports 2023, 42: 113478. PMID: 37991919, PMCID: PMC10785701, DOI: 10.1016/j.celrep.2023.113478.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsChromatin accessibilityProteomic compositionCellular senescenceTP53 stabilizationSARS-CoV-2 spikeCell-cell fusionPathogenic coronavirusesSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantsSenescence-associated inflammationSARS-CoV-2 infectionMiddle East respiratory syndromeAccessibility stateInflammatory cytokine releaseSevere respiratory infectionsSARS-CoV-2 variantsSignificant public health threatCoronavirus disease 2019SARS-CoV-2Public health threatBreakthrough infectionsRespiratory infectionsCytokine releaseSenescenceDisease 2019Respiratory syndromeIFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus
Ingle H, Makimaa H, Aggarwal S, Deng H, Foster L, Li Y, Kennedy E, Peterson S, Wilen C, Lee S, Suthar M, Baldridge M. IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus. Science Advances 2023, 9: eadi2562. PMID: 37703370, PMCID: PMC10499323, DOI: 10.1126/sciadv.adi2562.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIntestinal epithelial cellsTuft cellsUninfected bystander cellsIFN-λ signalingSource of IFNImmune cellsIntestinal infectionsLeading causeViral gastroenteritisMNoVNorovirus pathogenesisCellular tropismPotent antiviralEpidemic viral gastroenteritisEpithelial cellsBystander cellsIFNNorovirusAntiviralsInfectionMurine norovirusIntercellular communicationPersistent strainsCellsVivoMammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitors
Academic Achievements & Community Involvement
honor Young Faculty Award
National AwardDARPADetails09/01/2024honor Odyssey Award
National AwardSmith Family FoundationDetails01/01/2023honor Odyssey Award
National AwardSmith Family FoundationDetails11/01/2022United Stateshonor Young Physician-Scientist Award
International AwardAmerican Society for Clinical InvestigationDetails03/23/2021United Stateshonor Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award
Regional AwardDetails02/01/2020United States
Clinical Care
Overview
Clinical Specialties
Laboratory Medicine
Board Certifications
Clinical Pathology
- Certification Organization
- AB of Pathology
- Original Certification Date
- 2016
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- Vero-E6 cells expressing Cas9 were transduced with a novel genome-wide C. sabaeus (vervet monkey) library via lentivirus. The transduced cell population then received either mock treatment or SARS-CoV-2 under various culture conditions and multiplicities of infection.
- Mouse norovirus infection of tuft cells was observed in the small intestine of mice (Tuft cell marker DCLK1 in green; norovirus marker NS6/7 in red; nuclei in blue). The viral replication complex is located at the apical side of the tuft cell facing the gut lumen which may facilitate virus shedding and transmission.
News
- July 29, 2024Source: Yale News
What Shapes a Virus’s Pandemic Potential? SARS-CoV-2 Relatives Yield Clues
- July 11, 2024Source: Yale Ventures
11 Yale Projects Receive Awards from the Colton Center for Autoimmunity
- April 19, 2024
Immunobiology Graduate Student Arya Ökten wins the 3-Minute Thesis Competition
- February 22, 2024
Yale School of Medicine Receives a $575,000 Grant From PolyBio Research Foundation to Fund Long COVID Research
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