Featured Publications
Short-term consumption of highly processed diets varying in macronutrient content impair the sense of smell and brain metabolism in mice
Makhlouf M, Souza D, Kurian S, Bellaver B, Ellis H, Kuboki A, Al-Naama A, Hasnah R, Venturin G, da Costa J, Venugopal N, Manoel D, Mennella J, Reisert J, Tordoff M, Zimmer E, Saraiva L. Short-term consumption of highly processed diets varying in macronutrient content impair the sense of smell and brain metabolism in mice. Molecular Metabolism 2023, 79: 101837. PMID: 37977411, PMCID: PMC10724696, DOI: 10.1016/j.molmet.2023.101837.Peer-Reviewed Original ResearchConceptsMacronutrient contentIncrease food safetyGrain-based dietShort-term consumptionElectro-olfactogramFood safetyProcessed dietsFood processingBrain regionsBrain metabolismOdor-guided behaviorStandard chow dietShort-term intakeDietGlucose metabolism imagingHigh-fat dietFoodResponses to odorantsBrain glucose metabolismOlfactory mucosaModern dietFood consumptionChow dietChronic consumptionMetabolic phenotypeA 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell
Ruiz Tejada Segura M, Abou Moussa E, Garabello E, Nakahara T, Makhlouf M, Mathew L, Wang L, Valle F, Huang S, Mainland J, Caselle M, Osella M, Lorenz S, Reisert J, Logan D, Malnic B, Scialdone A, Saraiva L. A 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell. Cell Reports 2022, 38: 110547. PMID: 35320714, PMCID: PMC8995392, DOI: 10.1016/j.celrep.2022.110547.Peer-Reviewed Original ResearchCongenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease
Kubo S, Fritz J, Raquer-McKay H, Kataria R, Vujkovic-Cvijin I, Al-Shaibi A, Yao Y, Zheng L, Zou J, Waldman A, Jing X, Farley T, Park A, Oler A, Charles A, Makhlouf M, AbouMoussa E, Hasnah R, Saraiva L, Ganesan S, Al-Subaiey A, Matthews H, Flano E, Lee H, Freeman A, Sefer A, Sayar E, Çakır E, Karakoc-Aydiner E, Baris S, Belkaid Y, Ozen A, Lo B, Lenardo M. Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease. Nature Immunology 2021, 23: 75-85. PMID: 34937930, PMCID: PMC11060421, DOI: 10.1038/s41590-021-01093-y.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsADAM17 ProteinAnimalsCarrier ProteinsChildChild, PreschoolCitrobacter rodentiumColitisCytokinesEnterobacteriaceae InfectionsFemaleHEK293 CellsHumansInfant, NewbornMacrophagesMaleMiceMice, Inbred C57BLMutationPrimary Immunodeficiency DiseasesPseudomonas aeruginosaPseudomonas InfectionsSignal TransductionConceptsIRhom2 deficiencyLoss-of-function mutationsLocal microbial environmentLoss of iRhom2Diverse clinical phenotypesRecurrent respiratory infectionsWild-type miceRelease of cytokinesTumor necrosis factorHemorrhagic colitisCitrobacter rodentiumADAM17 metalloproteinaseFecal microbiotaSuperfamily membersRecurrent infectionsRecurrent pneumoniaTumor necrosisLung involvementColonic involvementHuman immunodeficiencyInflammatory colitisMicrobial environmentOral speciesPseudomonas aeruginosaColitis patientsDeconstructing the mouse olfactory percept through an ethological atlas
Manoel D, Makhlouf M, Arayata C, Sathappan A, Da'as S, Abdelrahman D, Selvaraj S, Hasnah R, Mainland J, Gerkin R, Saraiva L. Deconstructing the mouse olfactory percept through an ethological atlas. Current Biology 2021, 31: 2809-2818.e3. PMID: 33957076, PMCID: PMC8282700, DOI: 10.1016/j.cub.2021.04.020.Peer-Reviewed Original ResearchConceptsOlfactory perceptionMouse behaviorStudy of olfactory perceptionOdor perceptionBehavioral responsesPhysicochemical properties of odorantsHuman odor perceptionProperties of odorantsOdor identityOlfactory behaviorTarget odorOdorOdor concentrationPerceptionMiceBehaviorNon-humanResponseMultiple concentrationsDifferential regulation of the immune system in a brain-liver-fats organ network during short-term fasting
Huang S, Makhlouf M, AbouMoussa E, Segura M, Mathew L, Wang K, Leung M, Chaussabel D, Logan D, Scialdone A, Garand M, Saraiva L. Differential regulation of the immune system in a brain-liver-fats organ network during short-term fasting. Molecular Metabolism 2020, 40: 101038. PMID: 32526449, PMCID: PMC7339127, DOI: 10.1016/j.molmet.2020.101038.Peer-Reviewed Original ResearchConceptsShort-term fastingGene Ontology enrichment analysisOntology enrichment analysisReactome pathway analysisInnate immune signalingCombination of multivariate analysisImmune systemPriming of adaptive immunityChronic immunological disordersTranscriptional dynamicsGene setsGene OntologyWhite adipose tissueAdipose tissueProtein dataRNA sequencingBrown adipose tissueExpression analysisEnrichment analysisImmune signalingProfiles of miceDifferential regulationBiological pathwaysPathway analysisMolecular mechanismsA transcriptomic atlas of mammalian olfactory mucosae reveals an evolutionary influence on food odor detection in humans
Saraiva L, Riveros-McKay F, Mezzavilla M, Abou-Moussa E, Arayata C, Makhlouf M, Trimmer C, Ibarra-Soria X, Khan M, Van Gerven L, Jorissen M, Gibbs M, O'Flynn C, McGrane S, Mombaerts P, Marioni J, Mainland J, Logan D. A transcriptomic atlas of mammalian olfactory mucosae reveals an evolutionary influence on food odor detection in humans. Science Advances 2019, 5: eaax0396. PMID: 31392275, PMCID: PMC6669018, DOI: 10.1126/sciadv.aax0396.Peer-Reviewed Original ResearchConceptsOlfactory sensory neuronsChemosensory receptor gene familiesSpecies-specific adaptationsOlfactory sensory neurons subtypesCanonical olfactory receptorsReceptor gene familyOlfactory mucosa samplesMammalian olfactory mucosaGene familyEcological nichesMammalian evolutionTranscriptomic atlasAnalyzed speciesEvolutionary dynamicsRNA sequencingMammalian olfactory systemEvolutionary influencesOlfactory mucosaHomologous subtypesSensory neuronsOlfactory receptorsMucosa samplesOlfactory systemSubtypesMammalian olfactionAdipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
Ambrosi T, Scialdone A, Graja A, Gohlke S, Jank A, Bocian C, Woelk L, Fan H, Logan D, Schürmann A, Saraiva L, Schulz T. Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration. Cell Stem Cell 2017, 20: 771-784.e6. PMID: 28330582, PMCID: PMC5459794, DOI: 10.1016/j.stem.2017.02.009.Peer-Reviewed Original ResearchConceptsStem cell-basedHematopoietic regenerationAdipocyte accumulationStem cell-like characteristicsCell-like characteristicsBone resident cellsDipeptidyl peptidase-4Bone marrow cavityCompetitive repopulationLethal irradiationHematopoietic nicheBone marrowCell-basedPeptidase-4Osteogenic lineageAged animalsBone healingDiabetes therapyAdipocyte lineageBoneMarrow cavityAge-dependentMolecular identityObesityAdipogenic lineagesCombinatorial effects of odorants on mouse behavior
Saraiva L, Kondoh K, Ye X, Yoon K, Hernandez M, Buck L. Combinatorial effects of odorants on mouse behavior. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e3300-e3306. PMID: 27208093, PMCID: PMC4988607, DOI: 10.1073/pnas.1605973113.Peer-Reviewed Original ResearchConceptsTrace amine-associated receptorsOdor aversionBehavioral effectsInstinctive behavioral responsesBinary odor mixturesEffects of odorsOdorant receptorsAversive responsesPredator odorMouse behaviorOdor stimuliOdor mixturesOdor responsesOdor perceptionReceptor antagonismBehavioral responsesOdor detectionSingle receptorSensory inputInstinctive behaviorAversionOdorStereotyped natureReceptor inputMouse noseHierarchical deconstruction of mouse olfactory sensory neurons: from whole mucosa to single-cell RNA-seq
Saraiva L, Ibarra-Soria X, Khan M, Omura M, Scialdone A, Mombaerts P, Marioni J, Logan D. Hierarchical deconstruction of mouse olfactory sensory neurons: from whole mucosa to single-cell RNA-seq. Scientific Reports 2015, 5: 18178. PMID: 26670777, PMCID: PMC4680959, DOI: 10.1038/srep18178.Peer-Reviewed Original ResearchConceptsMature olfactory sensory neuronsOlfactory sensory neuronsRNA-seqOR genesGene expressionSingle-cell RNA-seqIntact OR genesOlfactory receptorsCell typesSingle-nucleotide polymorphismsOR-expressing OSNsOR gene expressionIntact olfactory receptorsNeuron-one receptor ruleCrude tissue samplesMonoallelic expressionNeuronal cell typesMouse olfactory mucosaMultiple cell typesChemosensory tissuesGenesCellular heterogeneityOlfactory mucosaSensory neuronsNon-neuronalHigh-throughput spatial mapping of single-cell RNA-seq data to tissue of origin
Achim K, Pettit J, Saraiva L, Gavriouchkina D, Larsson T, Arendt D, Marioni J. High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin. Nature Biotechnology 2015, 33: 503-509. PMID: 25867922, DOI: 10.1038/nbt.3209.Peer-Reviewed Original ResearchHigh-affinity olfactory receptor for the death-associated odor cadaverine
Hussain A, Saraiva L, Ferrero D, Ahuja G, Krishna V, Liberles S, Korsching S. High-affinity olfactory receptor for the death-associated odor cadaverine. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 19579-19584. PMID: 24218586, PMCID: PMC3845148, DOI: 10.1073/pnas.1318596110.Peer-Reviewed Original ResearchConceptsInnate behaviorsOlfactory receptorsSocial cuesOlfactory sensory neuronsNeural circuitsDetect cadaverineCarrion smellsVertebrate olfactionSensory neuronsAmino acids ornithinePhysiologically relevant sourceReceptorsConcomitant activationMolecular basisConcentration of cadaverineTAAR13cNeuronsSpeciesCuesOlfactionBehaviorSmellCadaverineA Large-Scale Analysis of Odor Coding in the Olfactory Epithelium
Nara K, Saraiva L, Ye X, Buck L. A Large-Scale Analysis of Odor Coding in the Olfactory Epithelium. Journal Of Neuroscience 2011, 31: 9179-9191. PMID: 21697369, PMCID: PMC3758579, DOI: 10.1523/jneurosci.1282-11.2011.Peer-Reviewed Original ResearchConceptsOlfactory sensory neuronsOdor qualityOdor recognitionMouse olfactory sensory neuronsOdorant receptorsEncode odor identityExpressed odorant receptorOdor identityOdor codingOlfactory epitheliumSensory neuronsPerceived odorMultiple odorantsSensory inputInnate behaviorsOdorLarge-scale analysisOR genesMiceCombinatorial codePositive Darwinian selection and the birth of an olfactory receptor clade in teleosts
Hussain A, Saraiva L, Korsching S. Positive Darwinian selection and the birth of an olfactory receptor clade in teleosts. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 4313-4318. PMID: 19237578, PMCID: PMC2657432, DOI: 10.1073/pnas.0803229106.Peer-Reviewed Original ResearchConceptsTrace amine-associated receptorsTAAR genesIntron gainGene familyClass IIIBony fishesOlfactory receptor neuronsPositive Darwinian selectionLocal positive selectionOlfactory receptor gene familyClass III genesOlfactory receptorsOlfactory receptor familyReceptor gene familyOlfactory epitheliumLigand-binding motifsFish genesTeleost lineageReceptor neuronsJawless vertebratesVertebrate evolutionIII genesPositive selectionDarwinian selectionEvolutionary dynamicsA novel olfactory receptor gene family in teleost fish
Saraiva L, Korsching S. A novel olfactory receptor gene family in teleost fish. Genome Research 2007, 17: 1448-1457. PMID: 17717047, PMCID: PMC1987349, DOI: 10.1101/gr.6553207.Peer-Reviewed Original ResearchConceptsOra genesGene pairsMulti-exon structureSpecies-specific expansionOlfactory receptor gene familyV1R-like genesOlfactory receptor familyReceptor gene familySpeciation eventsTeleost lineagePhylogenetic treePhylogenetic analysisGene familyGene regulationGene repertoireGene functionOlfactory epithelium of zebrafishTeleost familiesTeleost speciesOrthologsTeleost fishGenesNegative selectionTeleostFish species
2024
Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice
Rinne C, Soultoukis G, Oveisi M, Leer M, Schmidt-Bleek O, Burkhardt L, Bucher C, Moussa E, Makhlouf M, Duda G, Saraiva L, Schmidt-Bleek K, Schulz T. Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice. Frontiers In Endocrinology 2024, 15: 1394263. PMID: 38904042, PMCID: PMC11188307, DOI: 10.3389/fendo.2024.1394263.Peer-Reviewed Original ResearchConceptsBone marrow adipose tissueTrabecular bone lossAged miceCaloric restrictionBone lossEndocrine profileMale C57BL6J miceCardio-metabolic diseasesTime of CRAge-matched littermatesBiochemical lipid profilesAssess bone microstructureFree food accessC57BL6J miceBone healthYoung miceContext of agingMale miceDietary interventionNutritional interventionAnatomical localizationLipid profileAdipogenic gene expressionBone dysfunctionTrabecular bone structureConserved genes regulating human sex differentiation, gametogenesis and fertilization
Fakhro K, Awwad J, Garibova S, Saraiva L, Avella M. Conserved genes regulating human sex differentiation, gametogenesis and fertilization. Journal Of Translational Medicine 2024, 22: 473. PMID: 38764035, PMCID: PMC11103854, DOI: 10.1186/s12967-024-05162-2.Peer-Reviewed Original ResearchConceptsFertility phenotypesReproductive biologyMechanisms of gene functionNewly-discovered genesHuman reproductive biologyCharacterization of genesLoss-of-function mutationsFundamental reproductive processesNext-generation sequencingGenome editing technologyConserved genesFunctional genomicsGene functionFunctional characterizationConsanguineous populationsSex differentiationGenesReproductive tissuesMonogenic causeMolecular mechanismsHuman reproductive tissuesEditing technologyReproductive processesPhenotypeFertility disorders
2023
Genome-Wide RNA Tomography in the Mouse Whole Olfactory Mucosa
Moussa E, Makhlouf M, Mathew L, Saraiva L. Genome-Wide RNA Tomography in the Mouse Whole Olfactory Mucosa. Methods In Molecular Biology 2023, 2710: 19-30. PMID: 37688721, DOI: 10.1007/978-1-0716-3425-7_2.Peer-Reviewed Original Research
2022
The Neanderthal inside us
Saraiva L. The Neanderthal inside us. Nature Reviews Genetics 2022, 24: 142-142. PMID: 36471017, DOI: 10.1038/s41576-022-00561-x.Peer-Reviewed Original ResearchThe quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice
Cootes T, Bhattacharyya N, Huang S, Daniel L, Bell-Anderson K, Stifter S, Chew T, Solon-Biet S, Saraiva L, Cai Y, Chen X, Simpson S, Feng C. The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice. Cell Reports 2022, 41: 111638. PMID: 36384123, DOI: 10.1016/j.celrep.2022.111638.Peer-Reviewed Original ResearchConceptsGrain-based chow dietOutcome of host-pathogen interactionsSusceptibility to influenzaHost resistance to infectionInterferon (IFN)-gHost-pathogen interactionsMortality to infectionDiet compositionInfluenza infectionResistance to infectionHost phenotypeChow dietInfection susceptibilityHost defenseImpact of diet compositionExtrinsic signalsMiceLaboratory rodent dietHeightened susceptibilityInfectionAdaptive homeostasisAIN93GRodent dietIndividual macronutrientsInfluenzaOdor blocking of stress hormone responses
Lee E, Saraiva L, Hanchate N, Ye X, Asher G, Ho J, Buck L. Odor blocking of stress hormone responses. Scientific Reports 2022, 12: 8773. PMID: 35610316, PMCID: PMC9130126, DOI: 10.1038/s41598-022-12663-x.Peer-Reviewed Original ResearchConceptsCorticotropin-releasing hormone neuronsBed nucleus of the stria terminalisOdor blockingHypothalamic corticotropin-releasing hormone neuronsInhibitory neuronsInhibition of excitatory neuronsBlood stress hormonesStress-induced increaseActivity of inhibitory neuronsActivate inhibitory neuronsHypothalamic ventromedial nucleusStress hormone responsesBed nucleusStria terminalisTransmit stress signalsPredator odorSocial confrontationVentromedial nucleusStress hormonesHormone neuronsAllay stressPhysical restraintExcitatory neuronsOdorHormonal responses