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 patientsInherited human c-Rel deficiency disrupts myeloid and lymphoid immunity to multiple infectious agents
Lévy R, Langlais D, Béziat V, Rapaport F, Rao G, Lazarov T, Bourgey M, Zhou Y, Briand C, Moriya K, Ailal F, Avery D, Markle J, Lim A, Ogishi M, Yang R, Pelham S, Emam M, Migaud M, Deswarte C, Habib T, Saraiva L, Moussa E, Guennoun A, Boisson B, Belkaya S, Martinez-Barricarte R, Rosain J, Belkadi A, Breton S, Payne K, Benhsaien I, Plebani A, Lougaris V, Di Santo J, Neven B, Abel L, S. C, Bousfiha A, Marr N, Bustamante J, Liu K, Gros P, Geissmann F, Tangye S, Casanova J, Puel A. Inherited human c-Rel deficiency disrupts myeloid and lymphoid immunity to multiple infectious agents. Journal Of Clinical Investigation 2021, 131: e150143. PMID: 34623332, PMCID: PMC8409595, DOI: 10.1172/jci150143.Peer-Reviewed Original ResearchConceptsCD4+ T cellsMemory CD4+ T cellsC-Rel deficiencyT cellsMyeloid cellsLymphoid cellsB cellsC-RelMultiple infectious agentsNaive CD4+ T cellsCD8+ T cellsAntigen-presenting cell functionConventional DC1sFrequency of NKMemory B cellsNaive T cellsNaive B cellsFunctional deficitsReduced IL-2 productionProduction of Th1Infectious agentsIL-23 productionIL-2 productionInduction of CD86 expressionB cell survivalHierarchical 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-neuronalA 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 code
2024
Conserved 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
A 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
2014
The 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