Featured Publications
Congenital 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 patientsDifferential 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 olfactionCombinatorial 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-neuronal
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
2022
Odor 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 responsesA Novel FGFR1 Missense Mutation in a Portuguese Family with Congenital Hypogonadotropic Hypogonadism
Fadiga L, Lavrador M, Vicente N, Barros L, Gonçalves C, Al-Naama A, Saraiva L, Lemos M. A Novel FGFR1 Missense Mutation in a Portuguese Family with Congenital Hypogonadotropic Hypogonadism. International Journal Of Molecular Sciences 2022, 23: 4423. PMID: 35457241, PMCID: PMC9026826, DOI: 10.3390/ijms23084423.Peer-Reviewed Original ResearchConceptsCongenital hypogonadotropic hypogonadismMissense mutationsFibroblast growth factor receptor 1Sequence-based prediction methodsPathogenesis of CHHFailure of pubertal developmentIdentified missense mutationsFibroblast growth factor receptor 1 geneHypogonadotropic hypogonadismWhole-exome sequencingNormosmic congenital hypogonadotropic hypogonadismHeterozygous missense mutationExome sequencingGenetic studiesGrowth factor receptor 1Mutation spectrumFibroblast growth factor receptor 1 proteinIncomplete penetranceGonadotropin-releasing hormoneReproductive endocrine disordersAffected siblingsAmino acidsMutationsGenetic defectsGenes
2020
Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms
Gerkin R, Ohla K, Veldhuizen M, Joseph P, Kelly C, Bakke A, Steele K, Farruggia M, Pellegrino R, Pepino M, Bouysset C, Soler G, Pereda-Loth V, Dibattista M, Cooper K, Croijmans I, Di Pizio A, Ozdener M, Fjaeldstad A, Lin C, Sandell M, Singh P, Brindha V, Olsson S, Saraiva L, Ahuja G, Alwashahi M, Bhutani S, D’Errico A, Fornazieri M, Golebiowski J, Hwang L, Öztürk L, Roura E, Spinelli S, Whitcroft K, Faraji F, Fischmeister F, Heinbockel T, Hsieh J, Huart C, Konstantinidis I, Menini A, Morini G, Olofsson J, Philpott C, Pierron D, Shields V, Voznessenskaya V, Albayay J, Altundag A, Bensafi M, Bock M, Calcinoni O, Fredborg W, Laudamiel C, Lim J, Lundström J, Macchi A, Meyer P, Moein S, Santamaría E, Sengupta D, Dominguez P, Yanik H, Hummel T, Hayes J, Reed D, Niv M, Munger S, Parma V, Boesveldt S, de Groot J, Dinnella C, Freiherr J, Laktionova T, Marino S, Monteleone E, Nunez-Parra A, Abdulrahman O, Ritchie M, Thomas-Danguin T, Walsh-Messinger J, Al Abri R, Alizadeh R, Bignon E, Cantone E, Cecchini M, Chen J, Guàrdia M, Hoover K, Karni N, Navarro M, Nolden A, Mazal P, Rowan N, Sarabi-Jamab A, Archer N, Chen B, Di Valerio E, Feeney E, Frasnelli J, Hannum M, Hopkins C, Klein H, Mignot C, Mucignat C, Ning Y, Ozturk E, Peng M, Saatci O, Sell E, Yan C, Alfaro R, Cecchetto C, Coureaud G, Herriman R, Justice J, Kaushik P, Koyama S, Overdevest J, Pirastu N, Ramirez V, Roberts S, Smith B, Cao H, Wang H, Birindwa P, Baguma M. Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms. Chemical Senses 2020, 46: bjaa081. PMID: 33367502, PMCID: PMC7799216, DOI: 10.1093/chemse/bjaa081.Peer-Reviewed Original ResearchConceptsSmell lossOlfactory lossOlfactory recoveryCOVID-19 laboratory test outcomePredictors of COVID-19Visual analog scale ratingsVisual analog scaleC19+Assess symptomsYes/no-questionsRespiratory symptom onsetCardinal symptomsIllnessSymptomsRespiratory illnessBest predictorsC19 groupSymptom onsetParticipantsChemosensory abilitiesIndividualsPredictorsSymptomatic COVID-19Cross-sectional studyAnalog scaleMore Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis
Parma V, Ohla K, Veldhuizen M, Niv M, Kelly C, Bakke A, Cooper K, Bouysset C, Pirastu N, Dibattista M, Kaur R, Liuzza M, Pepino M, Schöpf V, Pereda-Loth V, Olsson S, Gerkin R, Domínguez P, Albayay J, Farruggia M, Bhutani S, Fjaeldstad A, Kumar R, Menini A, Bensafi M, Sandell M, Konstantinidis I, Di Pizio A, Genovese F, Öztürk L, Thomas-Danguin T, Frasnelli J, Boesveldt S, Saatci Ö, Saraiva L, Lin C, Golebiowski J, Hwang L, Ozdener M, Guàrdia M, Laudamiel C, Ritchie M, Havlícek J, Pierron D, Roura E, Navarro M, Nolden A, Lim J, Whitcroft K, Colquitt L, Ferdenzi C, Brindha E, Altundag A, Macchi A, Nunez-Parra A, Patel Z, Fiorucci S, Philpott C, Smith B, Lundström J, Mucignat C, Parker J, van den Brink M, Schmuker M, Fischmeister F, Heinbockel T, Shields V, Faraji F, Santamaría E, Fredborg W, Morini G, Olofsson J, Jalessi M, Karni N, D’Errico A, Alizadeh R, Pellegrino R, Meyer P, Huart C, Chen B, Soler G, Alwashahi M, Welge-Lüssen A, Freiherr J, de Groot J, Klein H, Okamoto M, Singh P, Hsieh J, Reed D, Hummel T, Munger S, Hayes J, Abdulrahman O, Dalton P, Yan C, Voznessenskaya V, Chen J, Sell E, Walsh-Messinger J, Archer N, Koyama S, Deary V, Roberts S, Yanik H, Albayrak S, Nováková L, Croijmans I, Mazal P, Moein S, Margulis E, Mignot C, Mariño S, Georgiev D, Kaushik P, Malnic B, Wang H, Seyed-Allaei S, Yoluk N, Razzaghi-Asl S, Justice J, Restrepo D. More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis. Chemical Senses 2020, 45: 609-622. PMID: 32564071, PMCID: PMC7337664, DOI: 10.1093/chemse/bjaa041.Peer-Reviewed Original ResearchConceptsChemosensory impairmentSmell lossAssociated with severe impairmentSelf-reported quantityNasal obstructionOlfactory abilityDifference scoresChemosensory modalitiesSevere impairmentPerceived nasal obstructionImpairmentClinical assessment groupClinical assessmentQuality of perceptionLaboratory testsInternational QuestionnaireReduction of smellParticipantsCOVID-19 diagnosisSmellObstructionCOVID-19Assessment Group
2017
Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing
Lam B, Cimino I, Polex-Wolf J, Kohnke S, Rimmington D, Iyemere V, Heeley N, Cossetti C, Schulte R, Saraiva L, Logan D, Blouet C, O'Rahilly S, Coll A, Yeo G. Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing. Molecular Metabolism 2017, 6: 383-392. PMID: 28462073, PMCID: PMC5404100, DOI: 10.1016/j.molmet.2017.02.007.Peer-Reviewed Original ResearchConceptsPOMC neuronsArcuate POMC neuronsControl of body weightUnbiased clustering analysisExpressed low levelsExpressed high levelsArcuate proopiomelanocortinRNA sequencingLeptin receptorAtlas of gene expressionSingle cell RNA sequencingGene expression profilesSingle-cell RNA sequencingCell RNA sequencingNeuronsBody weightLeptinInsulin receptorProopiomelanocortinHeterogeneous populationReceptorsExpression profilesGene expressionExpression
2015
Molecular and neuronal homology between the olfactory systems of zebrafish and mouse
Saraiva L, Ahuja G, Ivandic I, Syed A, Marioni J, Korsching S, Logan D. Molecular and neuronal homology between the olfactory systems of zebrafish and mouse. Scientific Reports 2015, 5: 11487. PMID: 26108469, PMCID: PMC4480006, DOI: 10.1038/srep11487.Peer-Reviewed Original ResearchConceptsDegree of molecular conservationYears of evolutionary divergenceVomeronasal organOlfactory mucosaOlfactory organChemosensory receptor genesOlfactory systemTranscriptome of miceDual olfactory systemEvolutionary divergenceMolecular conservationNeuronal homologRepertoire sizeRNA abundanceMolecular relationshipsCell-specific markersClasses of neuronsMolecular basisChemosensory receptorsMarker genesOrgans of rodentsAbsolute abundanceZebrafishReceptor geneVertebrates
2014
Olfactory Receptor Patterning in a Higher Primate
Horowitz L, Saraiva L, Kuang D, Yoon K, Buck L. Olfactory Receptor Patterning in a Higher Primate. Journal Of Neuroscience 2014, 34: 12241-12252. PMID: 25209267, PMCID: PMC4160765, DOI: 10.1523/jneurosci.1779-14.2014.Peer-Reviewed Original ResearchConceptsTrace amine-associated receptorsHuman trace amine-associated receptorDetect social cuesHuman olfactory perceptionOdorant receptorsMammalian olfactory systemOrganization of sensory inputsSocial cuesOlfactory perceptionOlfactory bulbOlfactory systemSensory inputInstinctive behaviorMouse nosePrimatesDifferent domainsOrganizational strategiesReceptor patternsMacaquesReceptorsCuesChemosensory receptorsMiceOlfactionBrainThe Olfactory Transcriptomes of Mice
Ibarra-Soria X, Levitin M, Saraiva L, Logan D. The Olfactory Transcriptomes of Mice. PLOS Genetics 2014, 10: e1004593. PMID: 25187969, PMCID: PMC4154679, DOI: 10.1371/journal.pgen.1004593.Peer-Reviewed Original ResearchConceptsVomeronasal receptorsVR genesProtein-coding genesProtein coding sequencesDeep RNA sequencingDistribution of abundanceEvidence of expressionCell-specific expressionReference genomeGene annotationMultiple malesMulti-exonQuantitative catalogOlfactory tissueMouse genomeCoding sequenceOR genesOlfactory-mediated behaviorsGenomic techniquesExpression microarraysRNA sequencingGene expressionGenesQuantitative RT-PCRSexual dimorphism
2008
Structural and functional diversification in the teleost S100 family of calcium-binding proteins
Kraemer A, Saraiva L, Korsching S. Structural and functional diversification in the teleost S100 family of calcium-binding proteins. BMC Ecology And Evolution 2008, 8: 48. PMID: 18275604, PMCID: PMC2266712, DOI: 10.1186/1471-2148-8-48.Peer-Reviewed Original ResearchConceptsS100 genesS100 gene familyGene familyJawless fishEF-handPatterns of gene gainCartilaginous fishCalcium-binding proteinLocal gene duplicationS100 familyMammalian family membersCell typesCalcium-mediated signalingEF-hand calcium-binding proteinS100 family membersGenomic arrangementTeleost genomesIntron/exon bordersGene lossGene duplicationGene gainFunctional diversificationS100 subfamilyFamily membersEvolutionary origin