2024
Role of Staphylococcus Aureus Superantigens in Cystic Fibrosis Lung Inflammation
Rajagopalan G, Tolentino J, Sun Y, Hu B, Koff J. Role of Staphylococcus Aureus Superantigens in Cystic Fibrosis Lung Inflammation. 2024, a6673-a6673. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6673.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 ResearchOptimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University
Würstle S, Lee A, Kortright K, Winzig F, An W, Stanley G, Rajagopalan G, Harris Z, Sun Y, Hu B, Blazanin M, Hajfathalian M, Bollyky P, Turner P, Koff J, Chan B. Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University. Scientific Reports 2024, 14: 2657. PMID: 38302552, PMCID: PMC10834462, DOI: 10.1038/s41598-024-52192-3.Peer-Reviewed Original ResearchConceptsEvolutionary selection pressurePhage characterizationPhage therapyPersistent bacterial infectionsBacteriophage therapyPhageSelection pressurePseudomonas aeruginosaInvestigational new drug applicationBacterial infectionsNew Drug ApplicationTherapyDrug applicationClinical applicationAutographiviridaeBacteriaPotential strategy
2023
Protracted Pulmonary Inflammation in IFN-gamma Deficient Mice Recovering From Cytokine Release Syndrome
Rajagopalan G, Sun Y, Hu B, Harris Z, Stanely G, Koff J. Protracted Pulmonary Inflammation in IFN-gamma Deficient Mice Recovering From Cytokine Release Syndrome. 2023, a1386-a1386. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a1386.Peer-Reviewed Original ResearchA Novel Zinc (II) Porphyrin Is Synergistic with PEV2 Bacteriophage against Pseudomonas aeruginosa Infections
Geyer J, Krupa K, Harris Z, Sun Y, Sharma L, Würstle S, Hu B, Stanley G, Rajagopalan G, Pellot E, Koff J, Robinson J. A Novel Zinc (II) Porphyrin Is Synergistic with PEV2 Bacteriophage against Pseudomonas aeruginosa Infections. Antibiotics 2023, 12: 735. PMID: 37107097, PMCID: PMC10135120, DOI: 10.3390/antibiotics12040735.Peer-Reviewed Original ResearchMinimum inhibitory concentrationMinimum bactericidal concentrationCystic fibrosisAntiviral activityPseudomonas aeruginosa infectionLife-threatening infectionsAntibiotic-resistant infectionsDose-dependent responsePulmonary infectionPotent bactericidal activityAeruginosa infectionMouse lungPsA populationImmune systemVivo modelLung cellsPSA cellsHealth concernNovel therapeuticsInfectionLung modelH441 cellsOpportunistic bacterial pathogenSignificant decreaseInhibitory concentration
2020
Contribution of Staphylococcal Enterotoxin B to Staphylococcus aureus Systemic Infection
Bae J, Da F, Liu R, He L, Lv H, Fisher E, Rajagopalan G, Li M, Cheung G, Otto M. Contribution of Staphylococcal Enterotoxin B to Staphylococcus aureus Systemic Infection. The Journal Of Infectious Diseases 2020, 223: 1766-1775. PMID: 32937658, PMCID: PMC8161638, DOI: 10.1093/infdis/jiaa584.Peer-Reviewed Original ResearchConceptsStaphylococcal enterotoxin BS. aureus pathogenesisCommunity-associated methicillin-resistant S. aureus infectionsMethicillin-resistant S. aureus infectionsEnterotoxin BS. aureus infectionMouse infection modelDrug development strategiesCytokine stormFatal exacerbationStaphylococcus aureus systemic infectionSuperantigenic toxinsAureus infectionMajor human pathogenST59 isolatesSystemic infectionInfection modelVirulence potentialInfectionStaphylococcus aureusPathogenesisHuman pathogensSEBExacerbationIsolatesIL-17A and IFN-gamma Play Distinct Roles in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome Induced by a Staphylococcal Superantigen
Rajagopalan G, Coutermarsh-Ott S, Sun Y, Hu B, Harris Z, Stanley G, Koff J. IL-17A and IFN-gamma Play Distinct Roles in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome Induced by a Staphylococcal Superantigen. 2020, a7708-a7708. DOI: 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7708.Peer-Reviewed Original Research
2019
Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality
Park K, Greenwood-Quaintance K, Cunningham S, Rajagopalan G, Chia N, Jeraldo P, Mandrekar J, Patel R. Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality. Microbial Pathogenesis 2019, 133: 103543. PMID: 31102653, DOI: 10.1016/j.micpath.2019.103543.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAnimalsBacteremiaBacterial AdhesionBase SequenceCell ProliferationDrug Resistance, BacterialFemaleHLA-DR3 AntigenHumansImmune EvasionMaleMethicillin-Resistant Staphylococcus aureusMiceMice, TransgenicMiddle AgedMinnesotaPolymerase Chain ReactionStaphylococcal InfectionsStaphylococcus aureusSuperantigensVirulenceVirulence FactorsConceptsMethicillin-susceptible S. aureusS. aureus bacteremiaAureus bacteremiaMedical CenterHLA-DR3 transgenic miceStaphylococcus aureus bacteremiaMinnesota Medical CenterLarge medical centerImmune evasion genesVirulence genesVirulence gene profilesNumber of deathsClinical dataClinical valueTransgenic miceClinical practiceIndividual PCR assaysWhole-genome sequencing analysisMortalitySAg genesSurvivorsLack of correlationBacteremiaWGS analysisFunctional assaysRuxolitinib, a selective JAK1/2 inhibitor, for the treatment of serious diseases caused by Staphylococcus aureus superantigens
Carnes H, Mehrkens B, Stegman M, Rajagopalan G. Ruxolitinib, a selective JAK1/2 inhibitor, for the treatment of serious diseases caused by Staphylococcus aureus superantigens. The Journal Of Immunology 2019, 202: 190.34-190.34. DOI: 10.4049/jimmunol.202.supp.190.34.Peer-Reviewed Original ResearchSystemic inflammatory response syndromeMulti-organ failureT cellsHLA-DR3 transgenic miceHLA class II moleculesVehicle-treated miceVivo studiesInflammatory response syndromeT cell subsetsToxic shock syndromeJAK 1/2 inhibitorSelective JAK1/2 inhibitorClass II moleculesStaphylococcus aureusDose-dependent mannerSerious diseaseJanus kinaseIL-17Response syndromeOrgan failureJAK1/2 inhibitorActivation markersCell subsetsShock syndromeIL-2
2018
Gastrointestinal and Extra-Intestinal Manifestations of IgG4–Related Disease
Miyabe K, Zen Y, Cornell LD, Rajagopalan G, Chowdhary VR, Roberts LR, Chari ST. Gastrointestinal and Extra-Intestinal Manifestations of IgG4–Related Disease. Gastroenterology 2018, 155: 990-1003.e1. PMID: 30012334, DOI: 10.1053/j.gastro.2018.06.082.Peer-Reviewed Original ResearchConceptsIgG4-RDPlasma cellsExtra-intestinal manifestationsHuman IgG4-RDSimilar immune reactionsRelapsing-remitting courseDense lymphoplasmacytic infiltrateTiters of autoantibodiesMulti-organ diseasePermanent organ damageObliterative phlebitisStoriform fibrosisAutoimmune etiologyMetachronous lesionsPrimary therapyExcellent prognosisLymph nodesLymphoplasmacytic infiltrateSerum levelsOrgan damageSerum IgG4Bile ductAutoimmune diseasesTypical presentationInflammatory responseCorrection: Both HIV-Infected and Uninfected Cells Express TRAILshort, Which Confers TRAIL Resistance upon Bystander Cells within the Microenvironment
Nie Z, Aboulnasr F, Natesampillai S, Burke S, Krogman A, Bren G, Chung T, Anderson J, Smart M, Katzmann D, Rajagopalan G, Cummins N, Badley A. Correction: Both HIV-Infected and Uninfected Cells Express TRAILshort, Which Confers TRAIL Resistance upon Bystander Cells within the Microenvironment. The Journal Of Immunology 2018, 201: ji1800867. PMID: 30006376, PMCID: PMC8592020, DOI: 10.4049/jimmunol.1800867.Peer-Reviewed Original ResearchDissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice
Rajagopalan G, Krogman A, Chowdhary V. Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice. The Journal Of Immunology 2018, 200: 117.3-117.3. DOI: 10.4049/jimmunol.200.supp.117.3.Peer-Reviewed Original ResearchHLA-DR3 transgenic miceToxic shock syndromeIL-17Transgenic miceHLA-DR3Shock syndromeAdaptive T cell responsesStaphylococcal toxic shock syndromeIL-17 family membersT cell responsesRole of IFNStaphylococcus aureus infectionS. aureusNon-specific activationTh17 cellsSerum levelsHLA-DRMice succumbedSystemic elevationTh1 cellsAureus infectionTissue injuryT cellsInfectious agentsIFNBoth HIV-Infected and Uninfected Cells Express TRAILshort, Which Confers TRAIL Resistance upon Bystander Cells within the Microenvironment
Nie Z, Aboulnasr F, Natesampillai S, Burke S, Krogman A, Bren G, Chung T, Anderson J, Smart M, Katzmann D, Rajagopalan G, Cummins N, Badley A. Both HIV-Infected and Uninfected Cells Express TRAILshort, Which Confers TRAIL Resistance upon Bystander Cells within the Microenvironment. The Journal Of Immunology 2018, 200: 1110-1123. PMID: 29263214, PMCID: PMC5808399, DOI: 10.4049/jimmunol.1701113.Peer-Reviewed Original ResearchConceptsTRAIL resistanceBystander cellsNeighboring bystander cellsUninfected bystander cellsType I IFNsOvercoming TRAIL ResistanceTRAIL receptor 1Apoptosis-inducing ligandHIV diseaseTLR9 agonistsImmune eliminationReceptor axisTRAILshortI IFNsSpecific AbsHIVReceptor 1Tumor cellsTRAIL sensitivityNormal cellsDominant negative ligandCellsSplice variantsMicroenvironmentKilling
2017
Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen
Chowdhary VR, Krogman A, Tilahun AY, Alexander MP, David CS, Rajagopalan G. Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen. The Journal Of Immunology 2017, 198: 4413-4424. PMID: 28468970, PMCID: PMC5471834, DOI: 10.4049/jimmunol.1601991.Peer-Reviewed Original ResearchConceptsDNT cellsDKO miceClass II moleculesΑβ TCRT cellsBacterial superantigensCD8 coreceptorIntact MHC class ILupus-like autoimmune diseaseEnterotoxin BHLA-DQ8 moleculesMHC class II moleculesAnti-nuclear AbsPeripheral T cellsDouble knockout miceMurine MHC class II moleculesMHC class IThymic positive selectionStaphylococcal enterotoxin BCD4/CD8 coreceptorsRegulatory cellsHLA-DR3Splenic CD3WT miceAutoimmune diseasesRandomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome*
Festic E, Carr G, Cartin-Ceba R, Hinds R, Banner-Goodspeed V, Bansal V, Asuni A, Talmor D, Rajagopalan G, Frank R, Gajic O, Matthay M, Levitt J. Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome*. Critical Care Medicine 2017, 45: 798-805. PMID: 28240689, PMCID: PMC5392150, DOI: 10.1097/ccm.0000000000002284.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAdministration, InhalationAdrenal Cortex HormonesAdrenergic beta-AgonistsAgedAged, 80 and overBiomarkersBudesonide, Formoterol Fumarate Drug CombinationDouble-Blind MethodDrug Therapy, CombinationFemaleHumansHypoxiaMaleMiddle AgedOxygenPatient AcuityRespiration, ArtificialRespiratory Distress SyndromeRisk FactorsUnited StatesConceptsAcute respiratory distress syndromeRespiratory distress syndromeBudesonide/formoterolDistress syndromeBeta agonistsMore patientsMechanical ventilationClinical trialsEarly treatmentFirst study drugAlveolar fluid clearanceEffective pharmacologic treatmentRandomized clinical trialsPlacebo bidCategorical changePlacebo groupStudy drugAdult patientsLung inflammationLung injuryPharmacologic treatmentPrimary outcomeMedian timeEmergency departmentImproved oxygenationPassive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus
Karau M, Tilahun M, Krogman A, Osborne B, Goldsby R, David C, Mandrekar J, Patel R, Rajagopalan G. Passive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus. Virulence 2017, 8: 1148-1159. PMID: 27925510, PMCID: PMC5711449, DOI: 10.1080/21505594.2016.1267894.Peer-Reviewed Original ResearchConceptsHLA-DR3 transgenic miceSystemic inflammatory responseOnset of infectionLethal pneumoniaTransgenic miceInflammatory responseB antibodiesHLA class II transgenic miceStrong systemic immune responsePolyclonal human IgGII transgenic miceRobust T cell activationSystemic immune responsesPro-inflammatory cytokinesLethal toxic shockAnti-toxin antibodiesToxigenic Staphylococcus aureusHuman IgGS. aureusStaphylococcus aureusT cell activationAnti-SEB antibodiesStaphylococcal enterotoxin BConventional mouse strainsProphylactic administration
2016
HLA‐DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin‐1 in a transgenic mouse model
Krogman A, Tilahun A, David CS, Chowdhary VR, Alexander MP, Rajagopalan G. HLA‐DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin‐1 in a transgenic mouse model. HLA 2016, 89: 20-28. PMID: 27863161, DOI: 10.1111/tan.12930.Peer-Reviewed Original ResearchToxic shock syndrome toxin-1Class II moleculesMHC class II moleculesHLA-DR allelesSyndrome toxin-1Transgenic miceImmune activationHuman leukocyte antigen (HLA) transgenic miceSpecific HLA class II allelesToxin 1Cytokine/chemokine responsesMajor histocompatibility complex (MHC) class II moleculesNonmenstrual toxic shock syndromeDifferent HLA-DR allelesHLA class II allelesStaphylococcal toxic shock syndrome toxin 1Severe organ pathologyDifferent HLA-DRB1 allelesMultiple immune parametersT cell expansionHLA-DRB1 allelesToxic shock syndromeTransgenic mouse modelOutcome of diseaseClass II allelesPhenotypic and Genotypic Characterization of Staphylococcus aureus Bloodstream Isolates in a Single Large Medical Center in Southeastern Minnesota
Park K, Greenwood-Quaintance K, Schmidt S, Uhl J, Cunningham S, Rajagopalan G, Patel R. Phenotypic and Genotypic Characterization of Staphylococcus aureus Bloodstream Isolates in a Single Large Medical Center in Southeastern Minnesota. Open Forum Infectious Diseases 2016, 3: 1068. DOI: 10.1093/ofid/ofw172.771.Peer-Reviewed Original ResearchInfluence of HLA‐DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model
Sheen Y, Rajagopalan G, Snapper C, Kita H, Wi C, Umaretiya P, Juhn Y. Influence of HLA‐DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model. HLA 2016, 88: 25-34. PMID: 27506953, PMCID: PMC6326101, DOI: 10.1111/tan.12851.Peer-Reviewed Original ResearchConceptsHouse dust miteHumoral immune responseAnti-pneumococcal polysaccharideHLA-DR polymorphismImmune responseHDM sensitizationIntact pneumococciHLA-DR3IgG responsesSerum titersTransgenic miceIntranasal house dust miteAnti-phosphorylcholine IgMHLA-DR3 miceLower humoral immune responseHalf of miceTransgenic mouse modelAllergic sensitizationPneumococcal diseaseIgM responseDR3 miceDust mitePneumococcal polysaccharideMouse modelA-IgGHLA-DR3 transgenic mice expressing Nur77-GFP reveal early and robust activation of T cells by superantigens during Staphylococcus aureus pneumonia.
Rajagopalan G, Karau M, Krogman A, Patel R, David C. HLA-DR3 transgenic mice expressing Nur77-GFP reveal early and robust activation of T cells by superantigens during Staphylococcus aureus pneumonia. The Journal Of Immunology 2016, 196: 66.9-66.9. DOI: 10.4049/jimmunol.196.supp.66.9.Peer-Reviewed Original ResearchSAg staphylococcal enterotoxin BT cell activationStaphylococcus aureus pneumoniaT cellsCell activationAureus pneumoniaStaphylococcal pneumoniaSerum cytokine/chemokine levelsCytokine/chemokine levelsHLA-DR3 transgenic miceT-cell activation markersEarly T cell activation markerRole of superantigensCell activation markersT cell subsetsTiming of administrationS. aureus strainsStaphylococcal enterotoxin BChemokine levelsDifferent time pointsHLA-DR3Activation markersCell subsetsCD69 expressionExperimental pneumonia