Featured Publications
Identifying candidate genes underlying isolated congenital anosmia
Kamarck M, Trimmer C, Murphy N, Gregory K, Manoel D, Logan D, Saraiva L, Mainland J. Identifying candidate genes underlying isolated congenital anosmia. Clinical Genetics 2023, 105: 376-385. PMID: 38148624, PMCID: PMC10932857, DOI: 10.1111/cge.14470.Peer-Reviewed Original ResearchConceptsIsolated congenital anosmiaWhole-exome sequencingCongenital anosmiaGene candidate listsLoss-of-function variantsSpectrum of genetic alterationsOlfactory transduction pathwayZinc ion bindingDeleterious variantsExome sequencingTransduction pathwaysGenetic alterationsOlfactory signalsNon-syndromicOlfactory functionAssociated with olfactionQuality of lifeGenesAnosmiaIon bindingEstimated 1VariantsOlfactionFamilyCNGA2Investigation of Genetic Causes in Patients with Congenital Heart Disease in Qatar: Findings from the Sidra Cardiac Registry
Okashah S, Vasudeva D, Jerbi A, Khodjet-El-khil H, Al-Shafai M, Syed N, Kambouris M, Udassi S, Saraiva L, Al-Saloos H, Udassi J, Al-Shafai K. Investigation of Genetic Causes in Patients with Congenital Heart Disease in Qatar: Findings from the Sidra Cardiac Registry. Genes 2022, 13: 1369. PMID: 36011280, PMCID: PMC9407366, DOI: 10.3390/genes13081369.Peer-Reviewed Original ResearchConceptsCongenital heart diseaseWhole-exome sequencingGenetic etiology of congenital heart diseaseAmerican College of Medical GeneticsPotential genetic variantsPotential causative variantsPathogenesis of congenital heart diseaseChromosomal abnormalitiesCardiac RegistryEtiology of congenital heart diseaseResults of genetic testingDevelopment of congenital heart diseaseCausative variantsHeart diseaseIdentified variantsMedical geneticsExome sequencingExome analysisGenetic variantsGenetic causeGenetic etiologyCHD phenotypesFunctional studiesGenetic defectsPotential variantsCongenital 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 survivalA 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 nose
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
2023
Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar
Mohammed I, Selvaraj S, Ahmed W, Al-Barazenji T, Hammad A, Dauleh H, Saraiva L, Al-Shafai M, Hussain K. Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar. International Journal Of Molecular Sciences 2023, 24: 16361. PMID: 38003551, PMCID: PMC10671262, DOI: 10.3390/ijms242216361.Peer-Reviewed Original ResearchConceptsCREB signaling pathwaysHeterozygous variantsSignaling pathwayVariants associated with obesityIn silico prediction toolsEffects of allelic variationFunctional impactIn silico analysisMonogenic obesityDownstream signaling cascadesLigand binding activityGT1-7 cellsObesity-related genesIdentified variantsAllelic variationFunctional characterizationSilico analysisSanger sequencingPathogenic variantsActivation of PKALeptin-melanocortin pathwaySignaling cascadesMonogenic forms of obesityGenesIn vitro analysisGenetic Variation and Sensory Perception of a Pediatric Formulation of Ibuprofen: Can a Medicine Taste Too Good for Some?
Mennella J, Kan M, Lowenthal E, Saraiva L, Mainland J, Himes B, Pepino M. Genetic Variation and Sensory Perception of a Pediatric Formulation of Ibuprofen: Can a Medicine Taste Too Good for Some? International Journal Of Molecular Sciences 2023, 24: 13050. PMID: 37685855, PMCID: PMC10487938, DOI: 10.3390/ijms241713050.Peer-Reviewed Original ResearchConceptsGenetic ancestryEuropean genetic ancestryTaste receptor genesIndependent of ancestryAfrican genetic ancestryGenetic variationFormulations of ibuprofenEpigenetic factorsAncestryReceptor geneDouble-blind cohort studyUrge to coughPerception of palatabilityRisk of accidental ingestionPersonality variationCohort studyPediatric formulationsSensory phenotypesThroat sensationChemesthetic sensationsMedicinal tasteTingling sensationPanelistsAdult panelistsDiverse populations
2022
The 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 macronutrientsInfluenzaA 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
2021
SysInflam HuDB, a Web Resource for Mining Human Blood Cells Transcriptomic Data Associated with Systemic Inflammatory Responses to Sepsis
Toufiq M, Huang S, Boughorbel S, Alfaki M, Rinchai D, Saraiva L, Chaussabel D, Garand M. SysInflam HuDB, a Web Resource for Mining Human Blood Cells Transcriptomic Data Associated with Systemic Inflammatory Responses to Sepsis. The Journal Of Immunology 2021, 207: 2195-2202. PMID: 34663591, PMCID: PMC8525868, DOI: 10.4049/jimmunol.2100697.Peer-Reviewed Original ResearchConceptsPublic transcriptome dataGene expression changesTranscriptome dataTranscriptomic datasetsBlood transcriptome datasetsSystemic inflammatory response to sepsisDisease susceptibilityResponse to infectionBlood gene signaturesExpression changesClinical metadataHost inflammatory responseInflammatory responseSystemic infectionDysregulated host inflammatory responseInflammatory response to sepsisGene signatureSystemic inflammatory responseMechanistic discoveriesSystemic inflammatory diseaseResponse to sepsisHeterogeneous diseaseWeb-based interfaceSepsis biomarkersInflammatory diseasesCalcium Signaling Regulates Autophagy and Apoptosis
Sukumaran P, Da Conceicao V, Sun Y, Ahamad N, Saraiva L, Selvaraj S, Singh B. Calcium Signaling Regulates Autophagy and Apoptosis. Cells 2021, 10: 2125. PMID: 34440894, PMCID: PMC8394685, DOI: 10.3390/cells10082125.Peer-Reviewed Original ResearchConceptsCell survivalOpposing functionCell death processMaintenance of cellular functionDepletion of Ca<sup>2+</sup>Pathogenesis of neurodegenerative diseasesPromote cell survivalNon-excitable cellsCytosolic Ca<sup>2+</sup> levelsCellular homeostasisCellular functionsAutophagy machineryER storesHuntington's diseaseDiverse functionsDeath processNeuronal developmentFunctional significanceNeurodegenerative diseasesPhysiological functionsNeurodegenerative conditionsApoptosisCellsHomeostasisImmune regulation
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
2018
Interspecific variation of olfactory preferences in flies, mice, and humans
Manoel D, Makhlouf M, Scialdone A, Saraiva L. Interspecific variation of olfactory preferences in flies, mice, and humans. Chemical Senses 2018, 44: 7-9. PMID: 30445540, PMCID: PMC6295792, DOI: 10.1093/chemse/bjy074.Peer-Reviewed Original Research
2015
Computational assignment of cell-cycle stage from single-cell transcriptome data
Scialdone A, Natarajan K, Saraiva L, Proserpio V, Teichmann S, Stegle O, Marioni J, Buettner F. Computational assignment of cell-cycle stage from single-cell transcriptome data. Methods 2015, 85: 54-61. PMID: 26142758, DOI: 10.1016/j.ymeth.2015.06.021.Peer-Reviewed Original ResearchConceptsCell cycle stageTranscriptomes of single cellsPopulation of cellsSingle-cell transcriptomic dataSingle cellsCell cycle signatureTranscriptome dataCellular statesRNA sequencingCell cycleExpression profilesCell typesTranscriptomePublished datasetsCaptured cellsCustomized predictorCellsComputational approachSupervised machine learning methodsMachine learning methodsNormalisation strategyComputational assignmentLearning methodsPCA-based approach
2009
The fifth class of Gα proteins
Oka Y, Saraiva L, Kwan Y, Korsching S. The fifth class of Gα proteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 1484-1489. PMID: 19164534, PMCID: PMC2635825, DOI: 10.1073/pnas.0809420106.Peer-Reviewed Original ResearchConceptsBirth-and-death mode of evolutionCharacteristics of GTP-binding proteinsGalpha proteinsVertebrate family membersAmino acid identityGTP-binding proteinsHeterotrimeric G proteinsN-terminal regionMode of evolutionAmino acid residuesG-boxGenomic structureAcid identityAnimal phylaConsensus sitesRT-PCR analysisGV proteinsJawless fishAcid residuesGA proteinsAnimal kingdomLarval tissuesAlpha subunitPartner moleculesFruit fly
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