2024
A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria
Chahine Z, Abel S, Hollin T, Barnes G, Chung J, Daub M, Renard I, Choi J, Vydyam P, Pal A, Alba-Argomaniz M, Banks C, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C, Bei A, Florens L, Ben Mamoun C, Vanderwal C, Le Roch K. A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria. Science 2024, 385: eadm7966. PMID: 39325875, DOI: 10.1126/science.adm7966.Peer-Reviewed Original ResearchConceptsP. falciparum malariaHumanized mouse modelPlasmodium falciparum</i> strainsIn vivo studiesParasite apicoplastDrug sensitivityTherapeutic profileVesicular traffickingGenomic analysisLipid biogenesisSecretory machineryAsexual replicationGenetic analysisReduced susceptibilityCellular traffickingApicoplast functionStrong efficacyMED6Sexual differentiationHemolytic activityDrug pipelineApicoplastKalihinolTraffickingMalariaA set of diagnostic tests for detection of active Babesia duncani infection
Chand M, Vydyam P, Pal A, Thekkiniath J, Darif D, Li Z, Choi J, Magni R, Luchini A, Tonnetti L, Horn E, Tufts D, Ben Mamoun C. A set of diagnostic tests for detection of active Babesia duncani infection. International Journal Of Infectious Diseases 2024, 147: 107178. PMID: 39025200, DOI: 10.1016/j.ijid.2024.107178.Peer-Reviewed Original ResearchB. microtiB. duncaniBlood samplesLife-threatening infectionsAntigen capture assayTick-borne diseasesFatal tick-borne diseaseP. falciparumBabesia genusScreening of blood samplesBabesia speciesB. divergensActive infectionAccurate diagnosisEffective disease managementPoint-of-care testingDiagnostic testsReservoir hostsBabesiaInfectionHuman babesiosisIntraerythrocytic parasitesImmunodominant antigensMolecular assaysCapture assayTafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis
Vydyam P, Pal A, Renard I, Chand M, Kumari V, Gennaro J, Mamoun C. Tafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis. The Journal Of Infectious Diseases 2024, 229: 161-172. PMID: 38169301, PMCID: PMC10786256, DOI: 10.1093/infdis/jiad315.Peer-Reviewed Original Research
2022
Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress
Ceccatelli Berti C, Gihaz S, Figuccia S, Choi J, Pal A, Goffrini P, Ben Mamoun C. Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress. International Journal Of Molecular Sciences 2022, 24: 435. PMID: 36613877, PMCID: PMC9820505, DOI: 10.3390/ijms24010435.Peer-Reviewed Original ResearchConceptsPantothenate Kinase-Associated NeurodegenerationFunctional conservationMitochondrial transit peptidePantothenate kinaseNormal cellular activitiesUse of yeastOverexpression of humanTransit peptideConserved functionYeast mutantsModel organismsPanK activityCellular functionsOxidative stressCellular conditionsMitochondrial homeostasisCellular cofactorsDefective growthKinase isoformsCellular activitiesMetabolic pathwaysYeastGenesMitochondrial dysfunctionBiochemical propertiesEpitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
Chand M, Choi J, Pal A, Singh P, Kumari V, Thekkiniath J, Gagnon J, Timalsina S, Gaur G, Williams S, Ledizet M, Mamoun C. Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti. Frontiers In Cellular And Infection Microbiology 2022, 12: 1039197. PMID: 36506011, PMCID: PMC9732259, DOI: 10.3389/fcimb.2022.1039197.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesAntigen detection assaysMajor immunogenic determinantMost clinical casesReliable biomarkersAntibody combinationsImmunogenic determinantsIntraerythrocytic life cycleClinical casesUnique epitopesBabesia microtiEpitope profilingHuman babesiosisTick-borne diseasesSignificant riseSerological profilingPlasma samplesAntibodiesSerological characterizationProtozoan parasitePublic healthInfectionAntigenDiseaseMammalian hostsBabesia duncani in Culture and in Mouse (ICIM) Model for the Advancement of Babesia Biology, Pathogenesis, and Therapy.
Kumari V, Pal A, Singh P, Mamoun C. Babesia duncani in Culture and in Mouse (ICIM) Model for the Advancement of Babesia Biology, Pathogenesis, and Therapy. Bio-protocol 2022, 12 PMID: 36620533, PMCID: PMC9795036, DOI: 10.21769/bioprotoc.4549.Peer-Reviewed Original ResearchMouse modelHuman red blood cellsRed blood cellsC3H/HeJ miceBlood cellsHuman babesiosisMalaria-like illnessB. duncaniImportant health impactsTick-borne diseaseBlood transfusionTick biteLethal infectionHeJ miceRare caseBabesia duncaniImmunocompromised miceAnimal modelsHuman infectionsParasitic diseasesBabesia microtiDiseaseElderly peopleIntraerythrocytic parasitesB. microtiHigh-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development
Gihaz S, Gareiss P, Choi JY, Renard I, Pal AC, Surovsteva Y, Chiu JE, Thekkiniath J, Plummer M, Hungerford W, Montgomery ML, Hosford A, Adams EM, Lightfoot JD, Fox D, Ojo KK, Staker BL, Fuller K, Ben Mamoun C. High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development. Structure 2022, 30: 1494-1507.e6. PMID: 36167065, PMCID: PMC10042587, DOI: 10.1016/j.str.2022.09.001.Peer-Reviewed Original ResearchConceptsCrystal structureHigh-throughput chemical screenHigh-resolution crystal structuresAntifungal drug developmentHigh-affinity inhibitorsEukaryotic pathogensChemical screenNew compoundsSingle chemotypeFunctional analysisLigand bindingAntifungal developmentPantothenate phosphorylationFungal isolatesPantothenate kinaseNew targetsFungiPanKPromising targetEnzymeDrug developmentNew mechanismCatalysisBiosynthesisKinaseSpecific and Sensitive Diagnosis of Babesia microti Active Infection Using Monoclonal Antibodies to the Immunodominant Antigen BmGPI12
Gagnon J, Timalsina S, Choi JY, Chand M, Singh P, Lamba P, Gaur G, Pal AC, Mootien S, Marcos LA, Mamoun C, Ledizet M. Specific and Sensitive Diagnosis of Babesia microti Active Infection Using Monoclonal Antibodies to the Immunodominant Antigen BmGPI12. Journal Of Clinical Microbiology 2022, 60: e00925-22. PMID: 36040206, PMCID: PMC9491189, DOI: 10.1128/jcm.00925-22.Peer-Reviewed Original ResearchConceptsB. microti infectionActive infectionMonoclonal antibodiesMicroti infectionTime of diagnosisMalaria-like illnessUrgent public health concernAntigen capture assayHost red blood cellsPublic health concernCapture assayEvaluation of clearanceElderly patientsRed blood cellsBlood transfusionDrug treatmentEarly diagnosisPosttreatment samplesBabesia microtiHealth concernInfected humansInfectionDiagnosisBlood cellsHuman babesiosisAn Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes
Singh P, Pal AC, Mamoun CB. An Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes. Pathogens 2022, 11: 599. PMID: 35631120, PMCID: PMC9146245, DOI: 10.3390/pathogens11050599.Peer-Reviewed Original ResearchBabesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo
Pal AC, Renard I, Singh P, Vydyam P, Chiu JE, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Mamoun C. Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo. The Journal Of Infectious Diseases 2022, 226: 1267-1275. PMID: 35512141, PMCID: PMC10233494, DOI: 10.1093/infdis/jiac181.Peer-Reviewed Original ResearchConceptsLethal infectionC3H/HeJ miceMalaria-like illnessB. duncaniMouse genetic backgroundSurvival outcomesHeJ miceSevere diseaseBabesia duncaniMouse modelDifferent mouse genetic backgroundsDrug susceptibilityBabesia microtiHuman babesiosisIntraerythrocytic parasitesUnique pathogenParasite loadMiceSpecies of BabesiaApicomplexa phylumInfectionBabesia parasitesFree merozoitesHuman erythrocytesGenetic background
2021
Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection
Chiu JE, Renard I, Pal AC, Singh P, Vydyam P, Thekkiniath J, Kumar M, Gihaz S, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Mamoun C. Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection. Antimicrobial Agents And Chemotherapy 2021, 65: 10.1128/aac.00662-21. PMID: 34152821, PMCID: PMC8370247, DOI: 10.1128/aac.00662-21.Peer-Reviewed Original ResearchConceptsEndochin-like quinolonesLethal infectionBlood-borne diseasesBlood-borne pathogensEffective therapyRelated apicomplexan parasitesExperimental therapiesLow doseMouse modelInfectious agentsHuman infectionsInfectionClinical candidatesStrong efficacyB. microtiExcellent safetyMode of actionTherapyErythrocytic developmentAtovaquoneEfficacyApicomplexan parasitesSafetyStructure-activity relationshipsParasitemiaEvidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients
George S, Pal AC, Gagnon J, Timalsina S, Singh P, Vydyam P, Munshi M, Chiu JE, Renard I, Harden CA, Ott IM, Watkins AE, Vogels CBF, Lu P, Tokuyama M, Venkataraman A, Casanovas-Massana A, Wyllie AL, Rao V, Campbell M, Farhadian SF, Grubaugh ND, Dela Cruz CS, Ko AI, Perez A, Akaho EH, Moledina DG, Testani J, John AR, Ledizet M, Mamoun CB, Team A. Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients. Kidney360 2021, 2: 924-936. PMID: 35373072, PMCID: PMC8791366, DOI: 10.34067/kid.0002172021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 spike proteinSARS-CoV-2Spike proteinUrine samplesSARS-CoV-2 infectionYale-New Haven HospitalCOVID-19 patientsAntigen capture assayDetectable viral RNANew Haven HospitalPositive PCR resultsPossible long-term consequencesSpike S1 proteinNP PCRChildren's HospitalNasopharyngeal swabsSARS-CoV-2 spike S1 proteinRenal abnormalitiesLong-term effectsCystatin CLong-term consequencesHospitalUrineViral RNAAlbuminuriaCytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle
Chiu JE, Renard I, George S, Pal A, Alday PH, Narasimhan S, Riscoe MK, Doggett JS, Mamoun C. Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle. The Journal Of Infectious Diseases 2021, 225: 135-145. PMID: 34139755, PMCID: PMC8730496, DOI: 10.1093/infdis/jiab321.Peer-Reviewed Original ResearchConceptsMitochondrial cytochrome bParasite life cycleWild-type alleleTick vectorParasite fitnessCytochrome bMutant parasitesMutant allelesErythrocytic cycleArthropod vectorsNymphal stagesBabesia parasitesMutationsLife cycleFitnessTick stagesResistance mutationsMalaria-like illnessB. microtiAllelesDrug resistance mutationsParasitesHuman babesiosisTicksHost
2020
Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B
Chiale C, Yarovinsky TO, Mason SW, Madina BR, Menon M, Krady MM, Moshkani S, Pal A, Almassian B, Rose JK, Robek MD, Nakaar V. Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B. Vaccines 2020, 8: 279. PMID: 32517032, PMCID: PMC7349932, DOI: 10.3390/vaccines8020279.Peer-Reviewed Original ResearchGriffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge
Lo MK, Spengler JR, Krumpe LRH, Welch SR, Chattopadhyay A, Harmon JR, Coleman-McCray JD, Scholte FEM, Hotard AL, Fuqua JL, Rose JK, Nichol ST, Palmer KE, O’Keefe B, Spiropoulou CF. Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge. The Journal Of Infectious Diseases 2020, 221: s480-s492. PMID: 32037447, PMCID: PMC7199786, DOI: 10.1093/infdis/jiz630.Peer-Reviewed Original ResearchConceptsSyrian golden hamstersGolden hamstersSevere acute respiratory syndrome coronavirusHuman immunodeficiency virus-1Acute respiratory syndrome coronavirusHepatitis C virusPathogenic zoonotic paramyxovirusImmunodeficiency virus-1Japanese encephalitis virusProphylactic evaluationC virusVirus challengeNiV infectionFatal encephalitisRespiratory diseaseSignificant protectionEncephalitis virusAntiviral activityZoonotic paramyxovirusVirus entrySyncytium formationGreater potencyVirus 1Nipah virusBroad-spectrum activity
2019
Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B
Yarovinsky TO, Mason SW, Menon M, Krady MM, Haslip M, Madina BR, Ma X, Moshkani S, Chiale C, Pal AC, Almassian B, Rose JK, Robek MD, Nakaar V. Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B. IScience 2019, 21: 391-402. PMID: 31704650, PMCID: PMC6889364, DOI: 10.1016/j.isci.2019.10.040.Peer-Reviewed Original ResearchHepatitis B virusChronic hepatitis BHepatitis BSerum HBV surface antigenVirus-like vesiclesLiver HBV RNAPersistent HBV replicationHBV surface antigenImmune exhaustionChronic hepatitisHBV antigensHBV infectionBooster immunizationCD8 TChronic modelHBV replicationImmunotherapeutic approachesLiver injuryNaive miceHBV RNAB virusCurrent treatmentSurface antigenUnmet needMultiple antigens
2018
A recombinant virus vaccine that protects against both Chikungunya and Zika virus infections
Chattopadhyay A, Aguilar PV, Bopp NE, Yarovinsky TO, Weaver SC, Rose JK. A recombinant virus vaccine that protects against both Chikungunya and Zika virus infections. Vaccine 2018, 36: 3894-3900. PMID: 29807712, DOI: 10.1016/j.vaccine.2018.05.095.Peer-Reviewed Original ResearchConceptsChikungunya virusZika virusA129 miceVesicular stomatitis virusChimeric vesicular stomatitis virusZika virus infectionWild-type miceSingle-dose vaccineRecombinant virus vaccineCo-circulating virusesLicensed vaccineSingle vaccinationZIKV infectionAntibody responsePandemic proportionsVirus vaccineVirus infectionAnimal modelsExperimental vaccinesVaccineMiceInfectionInvasive mosquito vectorsVSV glycoproteinVirus
2017
Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain
van den Pol AN, Mao G, Chattopadhyay A, Rose JK, Davis JN. Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain. Journal Of Virology 2017, 91: 10.1128/jvi.02154-16. PMID: 28077641, PMCID: PMC5331823, DOI: 10.1128/jvi.02154-16.Peer-Reviewed Original ResearchConceptsAdult mouse brainVesicular stomatitis virusVSV glycoprotein (G) geneAdult brainChimeric virusesOncolytic virusesVirus-like vesiclesChimeric vesicular stomatitis virusMouse brainSemliki Forest virusStomatitis virusPostnatal day 14 miceHealthy adult mouse brainRecombinant vesicular stomatitis virusKey immune mechanismsType I interferon responseG glycoproteinI interferon responseInterferon-stimulated genesDay 14 miceInfluenza H5N1 virusGlycoprotein geneNeurotropic natureIntranasal inoculationWild-type vesicular stomatitis virus
2016
Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection
Lauretti F, Chattopadhyay A, de Oliveira França RF, Castro-Jorge L, Rose J, da Fonseca BA. Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection. Human Vaccines & Immunotherapeutics 2016, 12: 2327-2333. PMID: 27185081, PMCID: PMC5027729, DOI: 10.1080/21645515.2016.1183857.Peer-Reviewed Original ResearchConceptsVaccine candidatesBALB/c miceImportant arbovirus diseaseCellular immune responsesDENV-2 infectionDengue-2 virusDENV vaccineHemorrhagic casesVSV virusesSubcutaneous routeHumoral responseC miceClinical trialsLethal infectionImmune responseDENV-2Vaccine vectorControl groupVirus expressionVaccineE expressionMiceFirst inoculationLethal dosesChallenge experiments
2014
In vitro evolution of high-titer, virus-like vesicles containing a single structural protein
Rose NF, Buonocore L, Schell JB, Chattopadhyay A, Bahl K, Liu X, Rose JK. In vitro evolution of high-titer, virus-like vesicles containing a single structural protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16866-16871. PMID: 25385608, PMCID: PMC4250146, DOI: 10.1073/pnas.1414991111.Peer-Reviewed Original ResearchConceptsVirus-like vesiclesStructural proteinsCapsid proteinCell surfaceLate domain motifsVesicular stomatitis virus glycoproteinVSV G proteinPlasmid-based systemOnly structural proteinSingle structural proteinDomain motifReplicase proteinsReplication factoriesMultiple point mutationsExtensive passagingG proteinsRNA repliconsRNA virusesPoint mutationsProteinEfficient packagingInnate immunityMutationsVirus glycoproteinVesicles