2024
Optimized 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
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 assays
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 responseBoth 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
Randomized 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
Influence 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-IgG
2015
Superantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia
Chung J, Greenwood-Quaintance K, Karau MJ, Tilahun A, Khaleghi SR, Chowdhary VR, David CS, Patel R, Rajagopalan G. Superantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia. Journal Of Leukocyte Biology 2015, 98: 271-281. PMID: 25979434, PMCID: PMC4501677, DOI: 10.1189/jlb.4a1214-577rr.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCatheter-Related InfectionsCatheters, IndwellingCD4-Positive T-LymphocytesEnterotoxinsGene DeletionHistocompatibility AntigensHumansKidneyLiverLungLymphocyte ActivationMiceMice, TransgenicReceptors, Antigen, T-Cell, alpha-betaSpleenStaphylococcal InfectionsStaphylococcus aureusSuperantigensConceptsS. aureusHLA-DR3 transgenic miceLong intravenous catheterSystemic immune activationSerum cytokine levelsSystemic inflammatory diseaseAbsence of bacteremiaMHC class II moleculesInvasive staphylococcal diseaseToxigenic S. aureusClinical S. aureus isolatesS. aureus isolatesClass II moleculesIsogenic S. aureusCytokine levelsHLA-DR3Immune activationInflammatory diseasesIntravenous cathetersStaphylococcal diseaseRole of SAgsDevice-associated infectionsT cellsClinical consequencesForeign body
2014
Superantigens in Staphylococcus aureus isolated from prosthetic joint infection
Kim C, Karau M, Greenwood-Quaintance K, Tilahun A, David C, Mandrekar J, Patel R, Rajagopalan G. Superantigens in Staphylococcus aureus isolated from prosthetic joint infection. Diagnostic Microbiology And Infectious Disease 2014, 81: 201-207. PMID: 25619753, PMCID: PMC4336809, DOI: 10.1016/j.diagmicrobio.2014.11.007.Peer-Reviewed Original ResearchSuperantigen profiling of Staphylococcus aureus infective endocarditis isolates
Chung J, Karau M, Greenwood-Quaintance K, Ballard A, Tilahun A, Khaleghi S, David C, Patel R, Rajagopalan G. Superantigen profiling of Staphylococcus aureus infective endocarditis isolates. Diagnostic Microbiology And Infectious Disease 2014, 79: 119-124. PMID: 24745820, PMCID: PMC4031024, DOI: 10.1016/j.diagmicrobio.2014.03.009.Peer-Reviewed Original ResearchConceptsSuperantigen genesSplenocyte proliferationS. aureusStaphylococcus aureus infective endocarditisMethicillin-susceptible S. aureusMethicillin-resistant S. aureusInfective endocarditis casesEnzyme-linked immunosorbent assayStaphylococcal enterotoxin AInfective endocarditisEndocarditis casesSuperantigen productionMouse splenocyte proliferationPCR-positive isolatesTSST-1EndocarditisImmunosorbent assayEnterotoxin AStaphylococcus aureusAureusProliferationIsolatesMortalityGenes
2013
Low Incidence of Spontaneous Type 1 Diabetes in Non-Obese Diabetic Mice Raised on Gluten-Free Diets Is Associated with Changes in the Intestinal Microbiome
Marietta E, Gomez A, Yeoman C, Tilahun A, Clark C, Luckey D, Murray J, White B, Kudva Y, Rajagopalan G. Low Incidence of Spontaneous Type 1 Diabetes in Non-Obese Diabetic Mice Raised on Gluten-Free Diets Is Associated with Changes in the Intestinal Microbiome. PLOS ONE 2013, 8: e78687. PMID: 24236037, PMCID: PMC3827256, DOI: 10.1371/journal.pone.0078687.Peer-Reviewed Original ResearchConceptsGluten-free dietNon-obese diabetic (NOD) miceAnti-diabetogenic effectsIncidence of hyperglycemiaNOD miceType 1 diabetesIntestinal microbiomeDietary glutenDiabetic miceSpontaneous type 1 diabetesAkkermansia speciesIncidence of diabetesIncidence of T1DIncidence of T1D.Blood glucose levelsIntestinal microbiome compositionLower incidenceGlucose levelsHigh incidenceAnimal studiesGut microfloraGut microbiomeHyperglycemiaIncidenceMice
2012
Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus
Chowdhary VR, Tilahun AY, Clark CR, Grande JP, Rajagopalan G. Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus. The Journal Of Immunology 2012, 189: 2054-2062. PMID: 22798666, PMCID: PMC3462343, DOI: 10.4049/jimmunol.1201097.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoantigensAutoimmune DiseasesCD28 AntigensCD4-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFlow CytometryFluorescent Antibody TechniqueHLA-DQ AntigensHumansInfusions, SubcutaneousLupus Erythematosus, SystemicMiceMice, TransgenicStaphylococcus aureusSuperantigensConceptsSystemic lupus erythematosusT cellsChronic exposureStaphylococcal enterotoxin BLupus erythematosusMouse MHC class II moleculesHLA-DQ8 transgenic miceMultisystem autoimmune inflammatory diseaseEnterotoxin BHLA-DQ8 miceAutoimmune inflammatory diseaseMHC class II moleculesTh1-type cytokinesMini-osmotic pumpsMononuclear cell infiltrationAnti-nuclear AbsClass II moleculesAbsence of diseaseChronic nasalIL-12Inflammatory infiltrateAutoimmune diseasesCell infiltrationInflammatory diseasesPathogenic roleThe impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia
Tilahun A, Karau M, Clark C, Patel R, Rajagopalan G. The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia. Microbes And Infection 2012, 14: 528-536. PMID: 22273732, DOI: 10.1016/j.micinf.2012.01.001.Peer-Reviewed Original ResearchConceptsStaphylococcal superantigensT cell activationChemokine levelsCell activationSystemic inflammatory response syndromeDR3 transgenic miceEfficacy of tacrolimusInflammatory response syndromeHuman leukocyte antigenImpact of tacrolimusPotent immunosuppressive agentPost-exposure treatmentT cell proliferationS. aureus strainsSystemic cytokinesGut dysfunctionSerum cytokinesResponse syndromeImmunosuppressive agentsLeukocyte antigenSystemic pathologyTacrolimusLethal pneumoniaPneumoniaTransgenic mice
2011
Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB
Tilahun M, Kwan A, Natarajan K, Quinn M, Tilahun A, Xie C, Margulies D, Osborne B, Goldsby R, Rajagopalan G. Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB. PLOS ONE 2011, 6: e27203. PMID: 22102880, PMCID: PMC3216929, DOI: 10.1371/journal.pone.0027203.Peer-Reviewed Original ResearchConceptsToxic shock syndromeLethal toxic shock syndromeHLA-DR3 transgenic miceStaphylococcal enterotoxin BChimeric human-mouse antibodyShock syndromeT cellsVivo protectionTransgenic micePartial protectionComplete protectionLethal dosesT cell populationsClass II MHCSignificant partial protectionAnti-SEB antibodiesHuman T cellsOnly partial protectionInflammatory cytokinesClinical safetyII MHCB antibodiesVivo modelChimeric antibodyEnterotoxin BHLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD
Deshmukh U, Sim D, Dai C, Kannapell C, Gaskin F, Rajagopalan G, David C, Fu S. HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD. Journal Of Autoimmunity 2011, 37: 254-262. PMID: 21868195, PMCID: PMC3372418, DOI: 10.1016/j.jaut.2011.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAutoantibodiesAutoantigensAutoimmunityEpitopes, T-LymphocyteFemaleHLA-DR3 AntigenHumansHybridomasImmunizationLupus Erythematosus, SystemicLymphocyte ActivationMiceMice, TransgenicMolecular MimicryPeptidesProtein BindingSnRNP Core ProteinsStreptococcus agalactiaeT-LymphocytesVibrio choleraeConceptsSystemic lupus erythematosusHLA-DR3 transgenic miceT cell epitopesHLA-DR3T cellsEpitope levelCell epitopesTransgenic miceMolecular mimicryPathogenesis of SLET cell epitope mimicryAutoreactive T cell clonesT hybridomasHLA-DR3 miceMicrobial peptidesAutoreactive T cellsProduction of autoantibodiesT cell responsesT cell clonesLupus erythematosusLupus autoantigensAutoimmune responseAutoimmune disordersImmunized miceEpitope mimicryHuman Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome
Tilahun A, Marietta E, Wu T, Patel R, David C, Rajagopalan G. Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome. American Journal Of Pathology 2011, 178: 2760-2773. PMID: 21641398, PMCID: PMC3124354, DOI: 10.1016/j.ajpath.2011.02.033.Peer-Reviewed Original ResearchConceptsToxic shock syndromeShock syndromeTransgenic miceSmall intestineHLA-DR3 transgenic miceHLA class II moleculesMultiple organ inflammationPotent T cell activatorsKey pathogenic eventClass II moleculesT cell activatorsGut dysfunctionKawasaki diseaseLiver failureHeavy infiltrationHigh morbidityD-GalN.Pathologic changesT lymphocytesExtrahepatic pathologyPathogenic eventsAbsorptive functionD-galactosamineSensitization modelMouse strainsHLA‐DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation
Rajagopalan G, Tilahun A, Iijima K, David C, Kita H, Juhn Y. HLA‐DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation. HLA 2011, 77: 589-592. PMID: 21447115, DOI: 10.1111/j.1399-0039.2010.01617.x.Peer-Reviewed Original ResearchConceptsHLA-DR3 transgenic miceHouse dust miteDust miteTransgenic miceTh2-predominant immune responseHouse dust mite extractInterleukin-13 levelsInflammatory cell countsBronchoalveolar lavage fluidTh2-type inflammationTransgenic mouse modelHLA-DR polymorphismAirway inflammationCytokine levelsBAL fluidEosinophil countHLA-DR3Childhood asthmaHLA-DR2Lavage fluidMite extractHLA-DRB1Immune responseInterleukin-4Mouse model
2010
Potent Neutralization of Staphylococcal Enterotoxin B by Synergistic Action of Chimeric Antibodies
Tilahun M, Rajagopalan G, Shah-Mahoney N, Lawlor R, Tilahun A, Xie C, Natarajan K, Margulies D, Ratner D, Osborne B, Goldsby R. Potent Neutralization of Staphylococcal Enterotoxin B by Synergistic Action of Chimeric Antibodies. Infection And Immunity 2010, 78: 2801-2811. PMID: 20308304, PMCID: PMC2876561, DOI: 10.1128/iai.01121-09.Peer-Reviewed Original ResearchConceptsStaphylococcal enterotoxin BT cell receptorT cell populationsT cell activationHLA-DR3 transgenic miceMouse mAbsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsEnterotoxin BCross-linking T-cell receptorsAntigen-independent proliferationClass II major histocompatibility complex moleculesBlood mononuclear cellsAntigen-presenting cellsChimeric human-mouse antibodyMajor histocompatibility complex moleculesT cell proliferationAntigen-independent activationHistocompatibility complex moleculesAnti-SEB antibodiesCytokine productionMononuclear cellsCytokine secretionMHC-IIPotent neutralization
2008
HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases
Mangalam A, Rajagopalan G, Taneja V, David C. HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases. Advances In Immunology 2008, 97: 65-147. PMID: 18501769, DOI: 10.1016/s0065-2776(08)00002-3.Peer-Reviewed Original ResearchConceptsHLA class II transgenic miceClass II moleculesII transgenic miceCommon autoimmune diseaseAutoimmune diseasesInflammatory diseasesTransgenic miceClass II genesDQ allelesHLA class II associationsInsulin-dependent diabetes mellitusHLA class II moleculesHLA transgenic miceCD4 T cellsClass II associationsHuman class II moleculesAutoimmune disease developmentToxic shock syndromeT cell repertoireHLA class II genesHuman inflammatory diseasesSimilar antigenic epitopesMHC class II genesAutoimmune myocarditisDiabetes mellitus
2007
Renal Hemodynamic, Inflammatory, and Apoptotic Responses to Lipopolysaccharide in HO-1−/− Mice
Tracz M, Juncos J, Grande J, Croatt A, Ackerman A, Rajagopalan G, Knutson K, Badley A, Griffin M, Alam J, Nath K. Renal Hemodynamic, Inflammatory, and Apoptotic Responses to Lipopolysaccharide in HO-1−/− Mice. American Journal Of Pathology 2007, 170: 1820-1830. PMID: 17525251, PMCID: PMC1899452, DOI: 10.2353/ajpath.2007.061093.Peer-Reviewed Original ResearchConceptsHeme oxygenase-1Immune cellsNF-kappaBRenal cytokine expressionRenal hemodynamic responseRenal blood flowGene heme oxygenase-1Glomerular filtration rateHO-1 deficiencyBone marrow progenitorsWidespread apoptosisHO-1 geneRenal hemodynamicsSepsis syndromeSerum cytokinesSerum levelsTh1 cytokinesClinical outcomesTh2 cytokinesCytokine expressionFiltration rateInflammatory responseHemodynamic responseBlunted activationBlood flow