Penghua Wang, PhD
Assistant Professor AdjunctCards
Appointments
Contact Info
About
Titles
Assistant Professor Adjunct
Appointments
Infectious Diseases
Assistant Professor AdjunctPrimary
Other Departments & Organizations
Education & Training
- PhD
- National University of Singapore (2006)
- BA
- ZhongShan Medical University (1992)
Research
Overview
I am primarily interested in host-pathogen interaction, with a focus on RNA viruses in vivo and in vitro. Specifically, I wish to understand pathogenic mechanisms of viral infection at the cellular and animal levels, and study the molecular function of host genes that influence viral pathogenesis and the disease outcomes. On the host side, I am keen on the innate immune system, detection of viruses and initiation of antiviral immune response. On the virus side, I wish to understand the mechanisms of immune evasion.
The Flaviviridae family consists of a large number of ssRNA viruses that cause fatal human diseases. For example, West Nile virus (WNV) is the culprit of thousands of encephalitis/meningitis cases and deaths since 1999. Dengue virus (DENV) infects 50 to 100 million people worldwide a year with a mortality of 1–5% if untreated. Hepatitis C virus (HCV) affects ~3% of the world's population and causes 350,000 deaths yearly. I attempt to identify novel host factors that restrict or facilitate virus pathogenesis in vivo and in vitro. These factors may be regulators of host antiviral immune pathways or participants of viral life cycle including surface receptors mediating viral entry. Understanding the molecular mechanisms underlying the pathogenesis of these disease conditions and virus specific host immune response can advance the development of specific antiviral therapeutics and vaccines.
1. Roles of NLRs in antiviral immune responses and the pathogenesis of West Nile viral encephalitis
2. Roles of UBXNs in antiviral immune responses
Medical Research Interests
Public Health Interests
ORCID
0000-0002-7332-1871
Research at a Glance
Yale Co-Authors
Publications Timeline
Erol Fikrig, MD
Ruth R Montgomery, PhD
Huabing Li, PhD
Joao Pereira, PhD
Jonathan Bogan, MD
Joseph Madri, MD, PhD
Publications
2025
Genetic deficiency or pharmacological inhibition of cGAS–STING signalling suppresses kidney inflammation and fibrosis
Jiao B, An C, Du H, Tran M, Yang D, Zhao Y, Wang P, Hu Z, Zhou D, Wang Y. Genetic deficiency or pharmacological inhibition of cGAS–STING signalling suppresses kidney inflammation and fibrosis. British Journal Of Pharmacology 2025 PMID: 39833988, DOI: 10.1111/bph.17412.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseMacrophage proinflammatory activationDevelopment of renal fibrosisObstructive injuryCGAS-STING signalingProinflammatory activityCGAS-STINGRenal inflammationRenal fibrosisPharmacological inhibitionMyofibroblast formationDamaged tubular epithelial cellsCyclic GMP-AMP synthase (cGAS)-stimulatorBone marrow-derived macrophagesAttenuated kidney fibrosisMarrow-derived macrophagesCGAS-STING signaling pathwayTubular epithelial cellsSignaling in vitroCell-derived DNAPreclinical modelsTubular atrophySTING deficiencyInhibition of cGASKidney inflammation
2024
UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling
Harrison A, Yang D, Cahoon J, Geng T, Cao Z, Karginov T, Hu Y, Li X, Chiari C, Qyang Y, Vella A, Fan Z, Vanaja S, Rathinam V, Witczak C, Bogan J, Wang P. UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling. Nature Immunology 2024, 25: 2234-2246. PMID: 39567760, DOI: 10.1038/s41590-024-02004-7.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsRIG-I-like receptorsRIG-I-like receptor signalingCytosolic RIG-I-like receptorsAntiviral immunityPlasma membrane tetheringRNA virus infectionGlucose transportInnate antiviral immunityCytoplasmic RIG-I-like receptorsGolgi matrixGLUT4 translocationRLR signalingViral RNACell surfaceGLUT4GLUT4 expressionGlucose uptakeInterferon responseRNAGlycolytic reprogrammingVirus infectionHuman inflammatory myopathiesGolgiSignalUbiquitinA substitution at the cytoplasmic tail of the spike protein enhances SARS-CoV-2 infectivity and immunogenicity
Li Y, Zhang X, Tai W, Zhuang X, Shi H, Liao S, Yu X, Mei R, Chen X, Huang Y, Liu Y, Liu J, Liu Y, Zhu Y, Wang P, Tian M, Yu G, Li L, Cheng G. A substitution at the cytoplasmic tail of the spike protein enhances SARS-CoV-2 infectivity and immunogenicity. EBioMedicine 2024, 110: 105437. PMID: 39531918, PMCID: PMC11603013, DOI: 10.1016/j.ebiom.2024.105437.Peer-Reviewed Original ResearchConceptsS proteinCytoplasmic tailFERM-binding motifTrans-complementation systemSpike proteinAmino acid substitutionsProline-to-leucine substitutionSystematic bioinformatics analysisHigh-frequency mutationsSARS-CoV-2 virionsBinding motifAcid substitutionsSARS-CoV-2Natural selectionBioinformatics analysisEzrin/radixin/moesin proteinsMolecular mechanismsMutationsOmicron variantProteinVaccine developmentMRNA vaccinesGlobal disseminationSARS-CoV-2 Omicron sublineagesSublineagesAutoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation
Karginov T, Ménoret A, Leclair N, Harrison A, Chandiran K, Suarez-Ramirez J, Yurieva M, Karlinsey K, Wang P, O'Neill R, Murphy P, Adler A, Cauley L, Anczuków O, Zhou B, Vella A. Autoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation. Science 2024, 385: eadj1979. PMID: 39265028, DOI: 10.1126/science.adj1979.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsRNA-binding proteinsT cell fateT cell receptor sensitivityT cell receptorPoison exonGenomes of jawed vertebratesPosttranscriptional regulatory mechanismsResponse to antigen receptor stimulationAntigen receptor stimulationTranscriptional regulationJawed vertebratesAlternative splicingSignaling transcriptsT cell survivalRegulatory mechanismsTCR sensitivitySplicingT-cell receptor gene rearrangementEffector T cell expansionT cell responses to antigenTRA2BT cell expansionResponse to antigenGene rearrangementsHistocompatibility complexUBXN3B is crucial for B lymphopoiesis
Geng T, Yang D, Lin T, Harrison A, Wang B, Cao Z, Torrance B, Fan Z, Wang K, Wang Y, Yang L, Haynes L, Cheng G, Vella A, Flavell R, Pereira J, Fikrig E, Wang P. UBXN3B is crucial for B lymphopoiesis. EBioMedicine 2024, 106: 105248. PMID: 39018756, PMCID: PMC11287013, DOI: 10.1016/j.ebiom.2024.105248.Peer-Reviewed Original ResearchConceptsUbiquitin regulatory XPre-BCR signalingB cell receptorB lymphopoiesisKnockout miceValosin-containing proteinCaspase-3 protein levelsCell cycle arrestBone marrow transferNormal B lymphopoiesisUbiquitin ligaseIncreased viral loadCell-intrinsic mannerPathogenesis of severe acute respiratory syndrome coronavirus 2RNA sequencingCycle arrestDNA virusesCell survivalMarrow transferMultiple virusesSingle-cellImmunofluorescence microscopyViral loadMature BRespiratory virusesA naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes
Zhang L, Wang D, Shi P, Li J, Niu J, Chen J, Wang G, Wu L, Chen L, Yang Z, Li S, Meng J, Ruan F, He Y, Zhao H, Ren Z, Wang Y, Liu Y, Shi X, Wang Y, Liu Q, Li J, Wang P, Wang J, Zhu Y, Cheng G. A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes. Science 2024, 384: eadn9524. PMID: 38669573, DOI: 10.1126/science.adn9524.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsColony forming unitsFlavivirus envelope proteinCommensal microbiotaIrreversible conformational changesGlucose dehydrogenaseMosquito gutConformational changesGut lumenPrevent viral infectionGutBacteriumFlavivirus transmissionEnvelope proteinsVector competencePrevent viral entryViral entryRefractory to infectionDengue virusForming unitsField mosquitoesTransmission of dengue virusFlavivirusesMosquitoesSemifield conditionsAdult mosquitoesAn evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses
Wu L, Zhang L, Feng S, Chen L, Lin C, Wang G, Zhu Y, Wang P, Cheng G. An evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2317978121. PMID: 38593069, PMCID: PMC11032495, DOI: 10.1073/pnas.2317978121.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsNonstructural proteinsSingle-stranded RNA genomeER-associated degradationE3 ligase HRD1Individual functional proteinsFlavivirus infectionCellular fitnessRNA genomeUbiquitin systemFlavivirus NS4AFunctional proteinsFlavivirus proteinsLysine residuesMammalian hostsMosquito-borne flavivirusSmall molecule inhibitorsStructural proteinsHrd1Viral proteinsProgeny virionsUbiquitinPotential therapeutic targetDENV2 infectionProteinNS4AA mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission
Wang Z, Nie K, Liang Y, Niu J, Yu X, Zhang O, Liu L, Shi X, Wang Y, Feng X, Zhu Y, Wang P, Cheng G. A mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission. The EMBO Journal 2024, 43: 1690-1721. PMID: 38378891, PMCID: PMC11066113, DOI: 10.1038/s44318-024-00056-x.Peer-Reviewed Original ResearchConceptsMyeloid cellsExpression of neutrophil chemoattractantsViral transmissionInflux of myeloid cellsMosquito bite siteSalivary componentsInflux of neutrophilsSkin-resident macrophagesPotential prophylactic targetsFlavivirus transmissionNF-kB signalingMechanism of actionProphylactic targetsSystemic disseminationRecruits proteinsSalivary factorsLocal infectionNeutrophil chemoattractantMammalian hostsEfficient viral transmissionPhytochemical resveratrolDengue virusBite siteTransmission of ZikaProteinUBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors
Yang D, Geng T, Harrison A, Cahoon J, Xing J, Jiao B, Wang M, Cheng C, Hill R, Wang H, Vella A, Cheng G, Wang Y, Wang P. UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors. Nature Communications 2024, 15: 780. PMID: 38278841, PMCID: PMC10817939, DOI: 10.1038/s41467-024-45141-1.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsUbiquitin protein ligase E3 component N-recognin 5RIG-IImmune response to RNA virusesResponse to RNA virusesRetinoic acid-inducible gene ILysine 63-linked ubiquitinationAntiviral immune responseRNA virus infectionViral RNA sensorsKnockout cell linesInitiation of antiviral immune responsesBoost antiviral immune responseImmune responsePosttranslational regulationTranscriptional brakeGene IEpigenetic repressorsRNA virusesDe-SUMOylationRNA sensorsUbiquitinWild type littermatesIncreased viral replicationTRIM28Transcription
2022
UBXN3B Controls Immunopathogenesis of Arthritogenic Alphaviruses by Maintaining Hematopoietic Homeostasis
Geng T, Yang D, Lin T, Cahoon J, Wang P. UBXN3B Controls Immunopathogenesis of Arthritogenic Alphaviruses by Maintaining Hematopoietic Homeostasis. MBio 2022, 13: e02687-22. PMID: 36377866, PMCID: PMC9765034, DOI: 10.1128/mbio.02687-22.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsUbiquitin regulatory X domain-containing proteinDomain-containing proteinsDiverse cellular processesCell-intrinsic mannerCellular processesHematopoietic homeostasisPhysiological functionsRNA virus replicationEssential roleControl of infectionChikungunya virusHuman genomeArthritogenic alphavirusesImmune responseCHIKV replicationDNA virusesRNA virusesInnate immune responseVirus-specific immunoglobulin GO'nyong'nyong virusLong-term neurological disordersSignificant public health problemSerum cytokine levelsSpecific antiviral drugsHigh viral load
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