Craig B. Wilen, MD, PhD
Associate Professor TermCards
About
Research
Overview
Host-pathogen interaction, viral immunity
Medical Research Interests
Coronavirus; COVID-19; Immune Evasion; Immune System Diseases; Norovirus; RNA Viruses; Virology
Publications
2025
Norovirus co-opts NINJ1 for selective protein secretion
Song J, Zhang L, Moon S, Fang A, Wang G, Gheshm N, Loeb S, Cao P, Wallace J, Alfajaro M, Strine M, Beatty W, Jamieson A, Orchard R, Robinson B, Nice T, Wilen C, Orvedahl A, Reese T, Lee S. Norovirus co-opts NINJ1 for selective protein secretion. Science Advances 2025, 11: eadu7985. PMID: 40020060, PMCID: PMC11870086, DOI: 10.1126/sciadv.adu7985.Peer-Reviewed Original ResearchConceptsPlasma membrane ruptureDamage-associated molecular patternsNS1 secretionNinjurin-1Programmed cell deathAmino acid residuesViral replication sitesViral protein NS1CRISPR screensIntracellular viral proteinsMutagenesis studiesMembrane ruptureProtein NS1Unconventional pathwayCaspase-3Protein secretionViral proteinsReplication sitesCell deathMolecular patternsGenetic ablationNS1Pharmaceutical inhibitionDAMP releaseProteinCorrection: Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro M, Wei J, Dong H, Homer R, Ring A, Wilen C, Iwasaki A. Correction: Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2025, 222: e2020124102192025c. PMID: 40009071, PMCID: PMC11864074, DOI: 10.1084/jem.2020124102192025c.Peer-Reviewed Original Research
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 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, PMCID: PMC11665867, DOI: 10.1016/j.jconrel.2024.05.008.Peer-Reviewed Original ResearchAntigen 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 ResearchConceptsInterferon-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, 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 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 ResearchInterferon-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 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
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. PMCID: PMC11721133, DOI: 10.1038/s44298-023-00010-4.Peer-Reviewed Original ResearchDifferences 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 ResearchConceptsChromatin 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 syndrome
Academic Achievements & Community Involvement
Clinical Care
Overview
Craig B. Wilen, MD, PhD, is a laboratory medicine physician who focuses on diseases caused by viruses, including coronaviruses and noroviruses. He investigates how these viruses infect cells and how the immune system responds, striving to develop improved strategies for diagnosis, treatment, and prevention.
As an associate professor of laboratory medicine and immunobiology at Yale School of Medicine, Dr. Wilen conducts research on viral immunity and pathogenesis. His research aims to identify key mechanisms that can lead to better risk assessment and therapeutic approaches for viral infections. He discovered a receptor that noroviruses use to infect certain intestinal cells, helping researchers better understand how these infections can be controlled.
Dr. Wilen has been honored with the Odyssey Award from the Smith Family Foundation, the DARPA Young Faculty Award and is a member of the American Society for Clinical Investigation. He received his medical training from the University of Pennsylvania and completed residency in clinical pathology at Barnes-Jewish Hospital.
Clinical Specialties
Laboratory Medicine
News & Links
Media
- 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
- February 04, 2025
Yale University Joins Global Virus Network as Center of Excellence
- January 15, 2025
Craig Wilen, MD, PhD, elected to ASCI
- January 15, 2025Source: TODAY
Hand sanitizer isn't enough to kill norovirus, experts say. What should you do instead?
- January 14, 2025
ASCI Welcomes 5 New Members from YSM
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