Featured Publications
The human malaria parasite Plasmodium falciparum can sense environmental changes and respond by antigenic switching
Schneider V, Visone J, Harris C, Florini F, Hadjimichael E, Zhang X, Gross M, Rhee K, Mamoun C, Kafsack B, Deitsch K. The human malaria parasite Plasmodium falciparum can sense environmental changes and respond by antigenic switching. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2302152120. PMID: 37068249, PMCID: PMC10151525, DOI: 10.1073/pnas.2302152120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigenic VariationGene Expression RegulationHumansMalaria, FalciparumParasitesPlasmodium falciparumProtozoan ProteinsConceptsGene switchingGene expressionHistone methyltransferasesHuman malaria parasite Plasmodium falciparumMalaria parasite Plasmodium falciparumS-adenosylmethionineGene expression patternsMulticopy gene familiesVariant surface proteinsParasite Plasmodium falciparumHuman malaria parasiteIntracellular S-adenosylmethioninePrincipal methyl donorEpigenetic controlGene familyActive genesAntigenic switchingGene transcriptionNutrient availabilityExpression patternsMethylation modificationSAM metabolismGenetic modificationAntigenic variationSurface proteins
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 pipelineApicoplastKalihinolTraffickingMalaria
2022
Epitope 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 ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBabesiaBabesia microtiEpitopesGastropodaHumansImmunodominant EpitopesMalaria, FalciparumMammalsMiceConceptsMonoclonal 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 hosts
2020
Palmitoylated Proteins in Plasmodium falciparum‐Infected Erythrocytes: Investigation with Click Chemistry and Metabolic Labeling
Kilian N, Zhang Y, LaMonica L, Hooker G, Toomre D, Mamoun CB, Ernst AM. Palmitoylated Proteins in Plasmodium falciparum‐Infected Erythrocytes: Investigation with Click Chemistry and Metabolic Labeling. BioEssays 2020, 42: e1900145. PMID: 32342554, DOI: 10.1002/bies.201900145.Peer-Reviewed Original ResearchMeSH KeywordsClick ChemistryErythrocytesHumansMalaria, FalciparumMicroscopy, ElectronPlasmodium falciparumConceptsMetabolic labelingHuman malaria parasite Plasmodium falciparumProtein S-palmitoylationImportant post-translational modificationMalaria parasite Plasmodium falciparumComplex cell biologyPost-translational modificationsParasite Plasmodium falciparumTime-consuming generationAsexual developmental stagesPalmitoylated proteinsS-palmitoylationCell biologyP. falciparumTransgenic parasitesExtent of labelingDevelopmental stagesMicroscopy approachSingle-molecule switchingPlasmodium falciparum-infected erythrocytesFalciparum-infected erythrocytesPlasmodium falciparumFalciparumLabelingMicroscopic examinationAnti-PfGARP activates programmed cell death of parasites and reduces severe malaria
Raj DK, Das Mohapatra A, Jnawali A, Zuromski J, Jha A, Cham-Kpu G, Sherman B, Rudlaff RM, Nixon CE, Hilton N, Oleinikov AV, Chesnokov O, Merritt J, Pond-Tor S, Burns L, Jolly G, Ben Mamoun C, Kabyemela E, Muehlenbachs A, Lambert L, Orr-Gonzalez S, Gnädig NF, Fidock DA, Park S, Dvorin JD, Pardi N, Weissman D, Mui BL, Tam YK, Friedman JF, Fried M, Duffy PE, Kurtis JD. Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria. Nature 2020, 582: 104-108. PMID: 32427965, PMCID: PMC7372601, DOI: 10.1038/s41586-020-2220-1.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsAntibodies, ProtozoanAntigens, ProtozoanAotidaeApoptosisCaspasesChildCohort StudiesDNA, ProtozoanEnzyme ActivationErythrocytesFemaleHumansIntercellular Signaling Peptides and ProteinsKenyaMalaria VaccinesMalaria, FalciparumMaleMiceParasitesPlasmodium falciparumProtozoan ProteinsTanzaniaTrophozoitesVacuolesConceptsTrophozoite-infected erythrocytesSevere malariaParasite antigensLongitudinal cohort studyPlasma of childrenCell deathNon-human primatesCohort studyEffective vaccineTanzanian childrenParasite densityInvasion of hepatocytesStage parasitesMalariaPlasmodium falciparumAntibodiesFalciparumKenyan adolescentsVaccineAntigenErythrocytesDeathChildrenInvasionParasites
2019
Comparative 3D genome organization in apicomplexan parasites
Bunnik EM, Venkat A, Shao J, McGovern KE, Batugedara G, Worth D, Prudhomme J, Lapp SA, Andolina C, Ross LS, Lawres L, Brady D, Sinnis P, Nosten F, Fidock DA, Wilson EH, Tewari R, Galinski MR, Ben Mamoun C, Ay F, Le Roch KG. Comparative 3D genome organization in apicomplexan parasites. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 3183-3192. PMID: 30723152, PMCID: PMC6386730, DOI: 10.1073/pnas.1810815116.Peer-Reviewed Original ResearchConceptsGenome organizationGene expressionApicomplexan parasitesVirulence genesSpatial genome organizationPositioning of chromosomesRelated apicomplexan parasitesVirulence gene clusterClustering of centromeresHi-C experimentsStrong repressive effectHuman malaria parasiteChromosome foldingEukaryotic cellsGene familyGene clusterGenome modelGenomeGene clusteringMore virulent pathogensNuclear spaceRepressive effectGenesAntigenic variationVirulent pathogens
2015
Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening
Choi JY, Kumar V, Pachikara N, Garg A, Lawres L, Toh J, Voelker DR, Ben Mamoun C. Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening. Molecular Microbiology 2015, 99: 999-1014. PMID: 26585333, PMCID: PMC4898484, DOI: 10.1111/mmi.13280.Peer-Reviewed Original ResearchConceptsClass of enzymesDevelopment of antimicrobialsYeast genesMembrane biogenesisEukaryotic pathogensProenzyme processingMammalian cellsPhosphatidylserine decarboxylasePSD activityPhospholipid biosynthesisParasite enzymeEssential functionsGenetic studiesMetabolic analysisAmino acidsDecarboxylase enzymePhosphatidylethanolamine synthesisPosition 40Inhibitor screeningEssential roleYeastEnzymePlasmodium falciparumSuitable targetNovel class
2013
Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission
Bobenchik AM, Witola WH, Augagneur Y, Lochlainn L, Garg A, Pachikara N, Choi JY, Zhao YO, Usmani-Brown S, Lee A, Adjalley SH, Samanta S, Fidock DA, Voelker DR, Fikrig E, Mamoun C. Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 18262-18267. PMID: 24145416, PMCID: PMC3831454, DOI: 10.1073/pnas.1313965110.Peer-Reviewed Original ResearchConceptsAsexual replicationGametocyte developmentFunctional complementation assaysPhosphoethanolamine N-methyltransferaseHost serineComplementation assaysMalaria transmissionGenetic diversityPhosphoethanolamine methyltransferaseGametocyte differentiationFemale gametocytesSpecificity of inhibitionMetabolic analysisSynthesis of phosphatidylcholineGametocytogenesisChemical screeningPlasmodium speciesAnopheles mosquitoesN-methyltransferaseLow micromolar rangePathwayReplicationHuman erythrocytesParasitesGlobal burden