2025
Therapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice
Sharma L, Singh R, Ngeow C, van der Geest R, Duray A, Tolman N, McVerry B, Dela Cruz C, Alcorn J, Bain W, Robinson K. Therapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice. Physiological Reports 2025, 13: e70232. PMID: 39921246, PMCID: PMC11805821, DOI: 10.14814/phy2.70232.Peer-Reviewed Original ResearchConceptsMurine model of influenzaIL-6 deletionMRSA pneumoniaModel of influenzaInflammatory cell recruitmentIL-6Interferon-stimulated genesMurine modelCell recruitmentJAK inhibitionElevated levels of IL-6Tissue injuryLevels of IL-6IL-6 deficiencyJAK inhibitor baricitinibSuppression of cytokinesLimit tissue injuryLung tissue injurySecondary bacterial infectionInfluenza infectionJAK/STAT signaling pathwayBaricitinib treatmentInhibitory therapyClinical efficacyBacterial burdenDamage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection
Kim J, Yuan Y, Agaronyan K, Zhao A, Wang V, Gau D, Toosi N, Gupta G, Essayas H, Kaminski A, McGovern J, Yu S, Woo S, Lee C, Gandhi S, Saber T, Saleh T, Hu B, Sun Y, Ishikawa G, Bain W, Evankovich J, Chen L, Yun H, Herzog E, Dela Cruz C, Ryu C, Sharma L. Damage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection. Mucosal Immunology 2025 PMID: 39884393, DOI: 10.1016/j.mucimm.2025.01.008.Peer-Reviewed Original ResearchToll-like receptor 9Anti-influenza immunityToll-like receptor 9 activationImpaired viral clearanceViral clearanceMyeloid cellsTissue injuryInflammatory responseInfluenza infectionPersistent inflammationLung injuryTissue damageToll-like receptor 9 deficiencyReceptor 9Toll-like receptor 9 signalingToll-like receptor 9 ligandInfection of immune cellsInfluenza-infected individualsPersistent lung injuryTLR9-/- miceInfected myeloid cellsInflammatory lung injurySensing tissue damageUnmethylated CpG DNA sequencesMitochondrial DNA
2024
Early antiviral use and supplemental oxygen decrease the risk of secondary bacterial infections: a multi-centre, nested, case–control study
Zhu Y, Hu H, Guo X, Zhang H, Li D, Dela Cruz C, Xie W, Xie L, Sharma L, Chang D. Early antiviral use and supplemental oxygen decrease the risk of secondary bacterial infections: a multi-centre, nested, case–control study. Journal Of Hospital Infection 2024, 156: 87-95. PMID: 39701496, DOI: 10.1016/j.jhin.2024.12.005.Peer-Reviewed Original ResearchConceptsRisk of secondary bacterial infectionIncidence of secondary bacterial infectionSecondary bacterial infectionAge-adjusted Charlson Comorbidity IndexCase-control studyPropensity-score matchingBacterial infectionsCOVID-19 patientsParenteral nutritionSupplemental oxygenTreatment strategiesAssociated with significant protectionAssociated with decreased incidenceAssociated with increased incidenceConditional logistic regression analysisSusceptibility to secondary bacterial infectionsAssociated with protectionCharlson Comorbidity IndexLogistic regression analysisAssociated with significant increasesAntiviral useGastric tubeAntibacterial therapyComorbidity indexIntravenous injectionContext‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries
Feng J, Kim J, Wang V, Chang D, Liu H, Bain W, Robinson K, Jie Z, Kotenko S, Dela Cruz C, Sharma L. Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries. Physiological Reports 2024, 12: e70104. PMID: 39455422, PMCID: PMC11511623, DOI: 10.14814/phy2.70104.Peer-Reviewed Original ResearchConceptsIII interferon signalingType III interferon signalingLung injuryInterferon signalingBleomycin-induced weight lossInflammatory responseModel of lung injuryBacterial pathogen Pseudomonas aeruginosaAcute lung injuryPathogen Pseudomonas aeruginosaBacterial endotoxin LPSChemotherapeutic agent bleomycinType III interferonsAnti-inflammatory roleIncreased inflammatory signalingLate time pointsBleomycin modelKnockout miceEndotoxin LPSIII interferonsAntiviral cytokinesDay 3Inflammatory signalingEarly injuryImpaired recoveryBeneficial effects of early low-dose methylprednisolone with long-term treatment in ARDS
Hu H, Wei S, Huang J, Sharma L, Chang D. Beneficial effects of early low-dose methylprednisolone with long-term treatment in ARDS. European Journal Of Internal Medicine 2024, 129: 137-139. PMID: 38879352, DOI: 10.1016/j.ejim.2024.06.009.Peer-Reviewed Original ResearchClinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis
Xiao Z, Lin M, Song N, Wu X, Hou J, Wang L, Tian X, An C, Dela Cruz C, Sharma L, Chang D. Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis. IScience 2024, 27: 110110. PMID: 38974472, PMCID: PMC11225851, DOI: 10.1016/j.isci.2024.110110.Peer-Reviewed Original ResearchViral sepsisCausative agent of sepsisAgent of sepsisCases of sepsisSusceptibility to secondary bacterial infectionsNon-sepsis patientsSecondary bacterial infectionPlatelet activation pathwaysMetabolomic characteristicsPlatelet dysfunctionSepsis phenotypesClinical featuresSystemic disease phenotypeSepsis patientsSepsisCOVID-19 pathologyBacterial infectionsProteomic signatureDisease phenotypeComplement proteinsBacterial pathogensProteomic dataActivation pathwayFunctional consequencesPathway proteinsSingle-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury
Yuan Y, Sharma L, Tang W, Raredon M, Ahangari F, Khoury J, Wu D, Niklason L, Kaminski N. Single-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury. Physiology 2024, 39: 1314. DOI: 10.1152/physiol.2024.39.s1.1314.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisAcute lung injuryChronic obstructive pulmonary diseaseAcute respiratory distress syndromeAnalysis of cell-cell communicationVEGF-DMicrovascular nicheSingle-cell RNA-seqLung injury modelSingle-cell RNA-seq analysisLung injuryCell-cell communicationLigand-receptor pairsLPS-induced lung injury modelRNA-seqAdjacent cell typesPulmonary diseaseInjury modelHuman lung endothelial cellsBarrier functionImmune cell infiltrationTumor necrosis factor-aRespiratory distress syndromeLung vascular integrityGene expressionSingle Nucleotide Variation in CX3CL1 and Risk for Bacterial Pneumonia and ARDS
Inman K, Chernus J, Lee M, Zhao Y, Shah F, Mayr F, Sharma L, Bon J, Dela Cruz C, Alder J, Mcverry B, Strollo P, Zhang Y, Kitsios G, Feingold E, Bain W. Single Nucleotide Variation in CX3CL1 and Risk for Bacterial Pneumonia and ARDS. 2024, a7203-a7203. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a7203.Peer-Reviewed Original ResearchStreamlined Nucleus Isolation Protocol for Cryopreserved Mouse Lung Captures Non-immune Cell Types by Single-nucleus RNA Sequencing
Tolman N, Tabary M, Sharma L, Dela Cruz C, Alder J, Lee J, Chen K, Bain W. Streamlined Nucleus Isolation Protocol for Cryopreserved Mouse Lung Captures Non-immune Cell Types by Single-nucleus RNA Sequencing. 2024, a3315-a3315. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a3315.Peer-Reviewed Original ResearchEpidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxia-Induced Lung Injury
Harris Z, Sun Y, Korde A, Hu B, Sharma L, Manning E, Joerns J, Clark B, Stanley G, Shin H, Placek L, Unutmaz D, Chun H, Sauler M, Rajagopalan G, Zhang X, Wang H, Kang M, Koff J. Epidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxia-Induced Lung Injury. 2024, a6841-a6841. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6841.Peer-Reviewed Original ResearchAnti-inflammatory Roles of Type I Interferon Signaling in the Lung
Feng J, Liu Y, Kim J, Ahangari F, Kaminski N, Bain W, Jie Z, Dela Cruz C, Sharma L. Anti-inflammatory Roles of Type I Interferon Signaling in the Lung. 2024, a6230-a6230. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6230.Peer-Reviewed Original ResearchVEGF-D Is Enriched in the Human Lung Microvascular Niche and Improves Vascular Integrity During Acute Lung Injury
Yuan Y, Sharma L, Tang W, Raredon M, Ahangari F, Khoury J, Wu D, Niklason L, Kaminski N. VEGF-D Is Enriched in the Human Lung Microvascular Niche and Improves Vascular Integrity During Acute Lung Injury. 2024, a4694-a4694. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4694.Peer-Reviewed Original ResearchChitotriosidase Regulates Host Response to Influenza Lung Infection
Kim J, Amick A, Sharma L, Dela Cruz C. Chitotriosidase Regulates Host Response to Influenza Lung Infection. 2024, a4183-a4183. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4183.Peer-Reviewed Original ResearchIntranasal 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 virusCompartmentalized ocular lymphatic system mediates eye–brain immunity
Yin X, Zhang S, Lee J, Dong H, Mourgkos G, Terwilliger G, Kraus A, Geraldo L, Poulet M, Fischer S, Zhou T, Mohammed F, Zhou J, Wang Y, Malloy S, Rohner N, Sharma L, Salinas I, Eichmann A, Thomas J, Saltzman W, Huttner A, Zeiss C, Ring A, Iwasaki A, Song E. Compartmentalized ocular lymphatic system mediates eye–brain immunity. Nature 2024, 628: 204-211. PMID: 38418880, PMCID: PMC10990932, DOI: 10.1038/s41586-024-07130-8.Peer-Reviewed Original ResearchResponse to herpes simplex virusCentral nervous systemImmune response to herpes simplex virusPosterior eyeImmune responseTherapeutic immune responsesOptic nerve sheathCervical lymph nodesAdeno-associated virusCNS diseaseDeep cervical lymph nodesHerpes simplex virusImmune protected miceCentral nervous system tissueLymphatic drainage systemImmunological featuresAnatomical extensionNerve sheathOptic nerveGene therapyLymph nodesMultiple dosesSimplex virusLymphatic circuitLymphatic signalAnti-inflammatory roles of type I interferon signaling in the lung
Feng J, Liu Y, Kim J, Ahangari F, Kaminski N, Bain W, Jie Z, Dela Cruz C, Sharma L. Anti-inflammatory roles of type I interferon signaling in the lung. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 326: l551-l561. PMID: 38375579, DOI: 10.1152/ajplung.00353.2023.Peer-Reviewed Original ResearchType I interferon signalingIfnar1-/- miceI interferon signalingInflammatory cell responseInflammatory responseIfnar1-/-Bleomycin injuryCell responsesWild-type miceBroncho-alveolar lavageElevated inflammatory responsePersistent inflammatory responseChemotherapeutic agent bleomycinAnti-inflammatory roleClinically relevant stimuliAnti-inflammatory mechanismsMyeloid cellsPersistent inflammationLung injuryFibrotic remodelingBacterial clearanceRIG-I signalingNOD-like receptor signalingLung tissueReceptor signalingDevelopmental changes in lung function of mice are independent of sex as a biological variable
Bärnthaler T, Ramachandra A, Ebanks S, Guerrera N, Sharma L, Dela Cruz C, Humphrey J, Manning E. Developmental changes in lung function of mice are independent of sex as a biological variable. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 326: l627-l637. PMID: 38375577, PMCID: PMC11380952, DOI: 10.1152/ajplung.00120.2023.Peer-Reviewed Original ResearchPulmonary function testsWeeks of ageStatic complianceMale miceInspiratory capacityLung functionBody weight-basedHuman lung pathologiesLung function of miceFemale C57BL/6J miceLung function parametersSex-dependent changesFunction of miceMeasures of lung functionIndependent of sexPreclinical modelsFemale miceC57BL/6J miceLung pathologyFunction testsMiceWeight-basedLungLung disease researchWeeksBeneficial and Detrimental Effects of Cytokines during Influenza and COVID-19
Chang D, Dela Cruz C, Sharma L. Beneficial and Detrimental Effects of Cytokines during Influenza and COVID-19. Viruses 2024, 16: 308. PMID: 38400083, PMCID: PMC10892676, DOI: 10.3390/v16020308.Peer-Reviewed Original ResearchConceptsDetrimental effects of cytokinesEffects of cytokinesSignaling moleculesUnfavorable outcomeMyriad processesPathological functionsCytokine effectsInflammatory cytokinesAntiviral cytokinesCytokinesViral infectionDisease severityPathological consequencesHomeostatic functionsOrganism deathDisease
2023
The emergence of influenza B as a major respiratory pathogen in the absence of COVID-19 during the 2021–2022 flu season in China
Chang D, Lin M, Song N, Zhu Z, Gao J, Li S, Liu H, Liu D, Zhang Y, Sun W, Zhou X, Yang B, Li Y, Wang L, Xiao Z, Li K, Xing L, Xie L, Sharma L. The emergence of influenza B as a major respiratory pathogen in the absence of COVID-19 during the 2021–2022 flu season in China. Virology Journal 2023, 20: 189. PMID: 37620959, PMCID: PMC10463403, DOI: 10.1186/s12985-023-02115-x.Peer-Reviewed Original ResearchConceptsInfluenza BAverage ageCOVID-19Influenza-like illnessNumber of patientsMajor respiratory pathogenCOVID-19 testCOVID-19-related restrictionsCell death markersClinical characteristicsFever clinicYounger patientsAppropriate vaccinationPatient characteristicsSubstantial morbidityRespiratory virusesSeasonal virusesLaboratory findingsPositivity rateInfluenza ARespiratory pathogensPreventive strategiesSecondary infectionSevere casesFlu seasonAssociation Between COVID-19 Infection and Pulmonary Fibrosis: A Nested Case-Control Study
Najjar-Debbiny R, Barnett-Griness O, Khoury J, Gronich N, Weber G, Adir Y, Shteinberg M, Shneir S, Sharma L, Saliba W. Association Between COVID-19 Infection and Pulmonary Fibrosis: A Nested Case-Control Study. The American Journal Of Medicine 2023, 136: 1087-1093.e2. PMID: 37598922, DOI: 10.1016/j.amjmed.2023.07.020.Peer-Reviewed Original ResearchPulmonary fibrosisCase-control studyCOVID-19 severityCOVID-19Multivariable conditional logistic regression modelsNested Case-Control StudyConditional logistic regression modelsSevere COVID-19Prior COVID-19COVID-19 infectionLogistic regression modelsLargest healthcare providerUnderlying cohortCohort entrySignificant morbiditySurveillance biasOdds ratioSevere diseaseFibrosisHealthcare providersCoronavirus diseaseCalendar timePatientsCohortLag time
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply