2024
Intranasal 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 virusBeneficial 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
VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic targetEditorial: Beneficial and pathological roles of myeloid cells during COVID-19
Sharma L, Sengupta S, Roger T. Editorial: Beneficial and pathological roles of myeloid cells during COVID-19. Frontiers In Immunology 2023, 14: 1194826. PMID: 37081868, PMCID: PMC10111195, DOI: 10.3389/fimmu.2023.1194826.Commentaries, Editorials and LettersIntegrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability
Habet V, Li N, Qi J, Peng G, Charkoftaki G, Vasiliou V, Sharma L, Pober J, Dela Cruz C, Yan X, Pierce R. Integrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability. The Yale Journal Of Biology And Medicine 2023, 96: 23-42. PMID: 37009190, PMCID: PMC10052603, DOI: 10.59249/kfyz8002.Peer-Reviewed Original ResearchConceptsIntegrated stress responseProteomic analysisTranscriptional activityStress responseSingle-cell RNA sequencingCell RNA sequencingHuman pulmonary microvascular endothelial cellsMulti-omics approachCell type annotationRespiratory transport chainUnbiased proteomic analysisUpregulation of proteinsIngenuity Pathway AnalysisCardiopulmonary bypassCell clusteringProtective cellular responseFunctional cellular assaysDistinct cell populationsDEG analysisCellular phenotypesRNA sequencingPathway analysisTransport chainCellular responsesImmune cellsmicroRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mouseCoronaviruses, Lysosomes, and Secondary Bacterial Infections: Coronaviruses Outsmart the Host
Peng X, Dela Cruz C, Sharma L. Coronaviruses, Lysosomes, and Secondary Bacterial Infections: Coronaviruses Outsmart the Host. DNA And Cell Biology 2023, 42: 189-193. PMID: 36763591, DOI: 10.1089/dna.2023.0002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSecondary bacterial infectionCellular homeostatic functionsHomeostatic functionsExtensive cell deathBacterial infectionsLysosomal lumenLysosomal machineryKey organellesLysosomal pathwayUnique adaptationsExit cellsSevere acute respiratory syndrome coronavirus 2Cell deathCellular componentsAcute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Pathogen killingCoronavirus disease 2019LysosomesLysosomal enzymesLysosomal environmentCoronavirus 2Host immunityCausative agent
2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Ahangari F, Becker C, Foster DG, Chioccioli M, Nelson M, Beke K, Wang X, Justet A, Adams T, Readhead B, Meador C, Correll K, Lili LN, Roybal HM, Rose KA, Ding S, Barnthaler T, Briones N, DeIuliis G, Schupp JC, Li Q, Omote N, Aschner Y, Sharma L, Kopf KW, Magnusson B, Hicks R, Backmark A, Dela Cruz CS, Rosas I, Cousens LP, Dudley JT, Kaminski N, Downey GP. Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1463-1479. PMID: 35998281, PMCID: PMC9757097, DOI: 10.1164/rccm.202010-3832oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisHuman precision-cut lung slicesPrecision-cut lung slicesPulmonary fibrosisNormal human lung fibroblastsEpithelial-mesenchymal transitionHuman lung fibroblastsFibrogenic pathwaysPreclinical modelsMurine modelLung slicesSrc kinase inhibitorLung fibroblastsKinase inhibitorsAmelioration of fibrosisSelective Src kinase inhibitorHuman lung fibrosisWhole lung extractsPotential therapeutic efficacyIPF diseaseIPF treatmentLung functionInflammatory cascadeLung fibrosisAntifibrotic efficacyConcurrent targeting of glycolysis in bacteria and host cell inflammation in septic arthritis
Kwon H, Yu K, Cahill S, Alder K, Dussik C, Kim S, Sharma L, Back J, Oh I, Lee F. Concurrent targeting of glycolysis in bacteria and host cell inflammation in septic arthritis. EMBO Molecular Medicine 2022, 14: emmm202115284. PMID: 36354099, PMCID: PMC9728052, DOI: 10.15252/emmm.202115284.Peer-Reviewed Original ResearchConceptsDrug dimethyl fumarateSeptic arthritisIntracellular MRSABacterial joint infectionSoft tissue infectionsAnti-inflammatory effectsInfection-associated inflammationNovel therapeutic paradigmContext of infectionConventional antibiotic treatmentHost cellsAdjuvant administrationSurgical treatmentTissue infectionsClinical symptomsInflammatory machineryJoint infectionBacterial burdenAntibiotic treatmentCell inflammationHost inflammationArthritisInflammationIntraarticular inflammationTherapeutic paradigmCoronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction.
Peng X, Kim J, Gupta G, Agaronyan K, Mankowski MC, Korde A, Takyar SS, Shin HJ, Habet V, Voth S, Audia JP, Chang D, Liu X, Wang L, Cai Y, Tian X, Ishibe S, Kang MJ, Compton S, Wilen CB, Dela Cruz CS, Sharma L. Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction. The Journal Of Immunology 2022, 209: 1314-1322. PMID: 36165196, PMCID: PMC9523490, DOI: 10.4049/jimmunol.2200198.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Bacterial infectionsMouse modelCoronavirus infectionLysosomal dysfunctionMajor health care challengeLung immune cellsLung tissue damageSecondary bacterial infectionImpair host immunityIL-1β releaseHealth care challengesCell deathPyroptotic cell deathBacterial killing abilityIL-1βBacterial clearanceImmune cellsSecondary infectionHost immunityAlveolar macrophagesTissue damageΒ-coronavirusStructural cellsCare challengesEpidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury
Harris ZM, Sun Y, Joerns J, Clark B, Hu B, Korde A, Sharma L, Shin HJ, Manning EP, Placek L, Unutmaz D, Stanley G, Chun H, Sauler M, Rajagopalan G, Zhang X, Kang MJ, Koff JL. Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury. Oxidative Medicine And Cellular Longevity 2022, 2022: 9518592. PMID: 36193076, PMCID: PMC9526641, DOI: 10.1155/2022/9518592.Peer-Reviewed Original ResearchConceptsAcute lung injuryEpidermal growth factor receptorAlveolar epithelial cellsLung injurySevere hyperoxiaEGFR inhibitionEpithelial cellsHyperoxia-Induced Lung InjuryRole of EGFRMurine alveolar epithelial cellsGrowth factor receptor inhibitionWorse clinical outcomesEpidermal growth factor receptor inhibitionHuman alveolar epithelial cellsWild-type littermatesPoly (ADP-ribose) polymeraseTerminal dUTP nickGrowth factor receptorClinical outcomesImproved survivalReceptor inhibitionLung repairProtective roleComplex roleEGFR deletion
2021
PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology.
Kim SH, Shin HJ, Yoon CM, Lee SW, Sharma L, Dela Cruz CS, Kang MJ. PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology. American Journal Of Respiratory Cell And Molecular Biology 2021, 64: 592-603. PMID: 33577398, PMCID: PMC8086043, DOI: 10.1165/rcmb.2020-0490oc.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBleomycinEpithelial CellsGene Expression RegulationHEK293 CellsHumansImmunity, InnateInflammasomesInfluenza A virusLungMiceMice, KnockoutMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinOrthomyxoviridae InfectionsPeroxisomesProtein AggregatesProtein BindingProtein KinasesPulmonary FibrosisSignal TransductionConceptsMAVS aggregationPINK1 deficiencyBimolecular fluorescence complementation analysisAntiviral innate immuneAppropriate cellular functionsKey molecular processesIntracellular signaling pathwaysInnate immune signalingComplementation analysisCellular functionsIntracellular perturbationsImmune signalingSignaling pathwaysPINK1Molecular processesMitochondria dysfunctionMAVSMAVS signalingMurine modelingSignalingFunctional significanceInnate immuneImportant roleRegulationNew roleRIPK3 Activates MLKL-mediated Necroptosis and Inflammasome Signaling during Streptococcus Infection.
Huang HR, Cho SJ, Harris RM, Yang J, Bermejo S, Sharma L, Dela Cruz CS, Xu JF, Stout-Delgado HW. RIPK3 Activates MLKL-mediated Necroptosis and Inflammasome Signaling during Streptococcus Infection. American Journal Of Respiratory Cell And Molecular Biology 2021, 64: 579-591. PMID: 33625952, PMCID: PMC8086037, DOI: 10.1165/rcmb.2020-0312oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsCalcium ChannelsCase-Control StudiesDisease Models, AnimalFemaleGene Expression RegulationHumansInflammasomesMacrophages, AlveolarMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMitochondriaMitochondrial Permeability Transition PoreNecroptosisNLR Family, Pyrin Domain-Containing 3 ProteinPneumonia, PneumococcalProtein KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesReceptor-Interacting Protein Serine-Threonine KinasesSignal TransductionStreptococcus pneumoniaeConceptsCommunity-acquired pneumoniaPneumococcal pneumoniaSevere pathological damageHealthy control subjectsPotential plasma markerNLRP3 inflammasome activationCommon bacterial pathogensMitochondrial permeability transition pore openingStreptococcal pneumoniaPlasma markersStreptococcus infectionBacterial clearanceControl subjectsPathological damageLeading causeMitochondrial reactive oxygenInflammasome activationMurine modelMitochondrial calcium uptakePneumoniaPermeability transition pore openingHuman studiesHigh mortalityInflammasome signalingTransition pore openingCutting Edge: Severe SARS-CoV-2 Infection in Humans Is Defined by a Shift in the Serum Lipidome, Resulting in Dysregulation of Eicosanoid Immune Mediators
Schwarz B, Sharma L, Roberts L, Peng X, Bermejo S, Leighton I, Casanovas-Massana A, Minasyan M, Farhadian S, Ko AI, Team Y, Dela Cruz CS, Bosio CM. Cutting Edge: Severe SARS-CoV-2 Infection in Humans Is Defined by a Shift in the Serum Lipidome, Resulting in Dysregulation of Eicosanoid Immune Mediators. The Journal Of Immunology 2021, 206: ji2001025. PMID: 33277388, PMCID: PMC7962598, DOI: 10.4049/jimmunol.2001025.Peer-Reviewed Original ResearchConceptsLipid mediatorsRisk factorsSevere diseaseSevere SARS-CoV-2 infectionHospitalized COVID-19 patientsSARS-CoV-2 infectionImportant immune regulatory roleSevere COVID-19COVID-19 patientsImmune regulatory roleProinflammatory lipid mediatorsCOVID-19Immunomodulatory eicosanoidsImmune mediatorsSerum lipidomeAdvanced agePatientsCOVID-19 pandemicCytochrome P450MortalityDiseaseDysregulationMediatorsLMS productsLipidomeJAK-inhibitor and type I interferon ability to produce favorable clinical outcomes in COVID-19 patients: a systematic review and meta-analysis
Walz L, Cohen AJ, Rebaza AP, Vanchieri J, Slade MD, Dela Cruz CS, Sharma L. JAK-inhibitor and type I interferon ability to produce favorable clinical outcomes in COVID-19 patients: a systematic review and meta-analysis. BMC Infectious Diseases 2021, 21: 47. PMID: 33430799, PMCID: PMC7797881, DOI: 10.1186/s12879-020-05730-z.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsType I interferonOdds of mortalityPositive clinical outcomesClinical outcomesI interferonICU admissionExcessive cytokine releaseType I interferon treatmentStandard treatment groupOdds of dischargeFavorable clinical outcomeNon-randomized trialsJanus kinase inhibitorSearch of MEDLINETerms of mortalityKinase inhibitor treatmentHospital dischargeCytokine releaseInterferon treatmentPotential antiviral candidatesNovel therapiesTreatment outcomesTreatment groupsAntiviral candidatesDisinfection of Pseudomonas aeruginosa from N95 respirators with ozone: a pilot study
Manning EP, Stephens MD, Dufresne S, Silver B, Gerbarg P, Gerbarg Z, Dela Cruz CS, Sharma L. Disinfection of Pseudomonas aeruginosa from N95 respirators with ozone: a pilot study. BMJ Open Respiratory Research 2021, 8: e000781. PMID: 33431507, PMCID: PMC7802653, DOI: 10.1136/bmjresp-2020-000781.Peer-Reviewed Original Research
2020
The kinetics of humoral response and its relationship with the disease severity in COVID-19
Ren L, Zhang L, Chang D, Wang J, Hu Y, Chen H, Guo L, Wu C, Wang C, Wang Y, Wang Y, Wang G, Yang S, Dela Cruz CS, Sharma L, Wang L, Zhang D, Wang J. The kinetics of humoral response and its relationship with the disease severity in COVID-19. Communications Biology 2020, 3: 780. PMID: 33311543, PMCID: PMC7733479, DOI: 10.1038/s42003-020-01526-8.Peer-Reviewed Original ResearchConceptsHumoral responseDisease severityReceptor-binding domainAntibody titersSpike proteinSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2COVID-19Respiratory syndrome coronavirus 2Titers of NAbsGeometric mean titersCOVID-19 patientsSyndrome coronavirus 2Coronavirus disease 2019Disease courseMean titersCoronavirus 2Antibody responseIgG antibodiesRisk factorsIg levelsImmunoglobulin ADisease 2019Severe casesModerate infectionsIdentification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2
Xiao X, Wang C, Chang D, Wang Y, Dong X, Jiao T, Zhao Z, Ren L, Dela Cruz CS, Sharma L, Lei X, Wang J. Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2. Frontiers In Immunology 2020, 11: 586572. PMID: 33324406, PMCID: PMC7723961, DOI: 10.3389/fimmu.2020.586572.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Therapeutic agentsAnti-coronaviral activitySARS-CoV-2 drugsWide therapeutic windowCOVID-19 infectionNovel therapeutic agentsEffective compoundsTherapeutic optionsReplication of coronavirusesSafe drugSevere diseaseTherapeutic windowHuman coronavirusesTherapeutic candidateUS FDAArbidol hydrochlorideIdentification of PotentTwo-step screenMillions of peopleSafety indexDrugsCOVID-19 pandemicFDACoronavirusSevere respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia
Gautam S, Cohen AJ, Stahl Y, Toro P, Young GM, Datta R, Yan X, Ristic NT, Bermejo SD, Sharma L, Restrepo M, Dela Cruz CS. Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia. Thorax 2020, 75: 974-981. PMID: 32826284, DOI: 10.1136/thoraxjnl-2020-214896.Peer-Reviewed Original ResearchConceptsPure viral infectionBacterial coinfectionViral infectionInfluenza infectionSevere respiratory viral infectionsAbility of procalcitoninRetrospective cohort studyViral respiratory infectionsRespiratory viral infectionsMarker of severityRespiratory viral illnessSevere viral infectionsSpecificity of procalcitoninCharacteristic curve analysisCellular modelHigher procalcitoninProcalcitonin expressionElevated procalcitoninCohort studyViral illnessRespiratory infectionsAntibiotic administrationBacterial pneumoniaSevere diseaseProcalcitoninDifferential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages
Chang D, Feng J, Liu H, Liu W, Sharma L, Dela Cruz CS. Differential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages. Innate Immunity 2020, 26: 618-626. PMID: 32762278, PMCID: PMC7556185, DOI: 10.1177/1753425920942582.Peer-Reviewed Original ResearchConceptsAkt pathwayEpithelial cellsCell typesKey cellular pathwaysLung epitheliumActivation of AktPhagocytic abilityMultiple cell typesAkt inhibitor MK2206Particular bacterial infectionsCellular pathwaysLung epithelial cellsMacrophage cell lineHost cellsBacterial infectionsRespiratory epithelial cellsCell proliferationType of infectionCell linesPathwayHost defenseDifferential rolesAktSC-79Cells