2024
Rare de novo damaging DNA variants are enriched in attention-deficit/hyperactivity disorder and implicate risk genes
Olfson E, Farhat L, Liu W, Vitulano L, Zai G, Lima M, Parent J, Polanczyk G, Cappi C, Kennedy J, Fernandez T. Rare de novo damaging DNA variants are enriched in attention-deficit/hyperactivity disorder and implicate risk genes. Nature Communications 2024, 15: 5870. PMID: 38997333, PMCID: PMC11245598, DOI: 10.1038/s41467-024-50247-7.Peer-Reviewed Original ResearchConceptsDNA sequencesRisk genesHigh-confidence risk genesWhole-exome DNA sequencingSequencing of familiesIdentified de novoLysine demethylase 5BDNA variantsTrio cohortBiological pathwaysGenesSequencing cohortGenetic factorsChildhood neurodevelopmental disordersAttention-deficit/hyperactivity disorderSequenceVariantsADHD riskNeurodevelopmental disordersKDM5BDNAMutationsFamilyLysineDiscovery
2023
Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene
Fernandez T, Williams Z, Kline T, Rajendran S, Augustine F, Wright N, Sullivan C, Olfson E, Abdallah S, Liu W, Hoffman E, Gupta A, Singer H. Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene. PLOS ONE 2023, 18: e0291978. PMID: 37788244, PMCID: PMC10547198, DOI: 10.1371/journal.pone.0291978.Peer-Reviewed Original ResearchConceptsRisk genesDe novo damaging variantsGene expression patternsWhole-exome DNA sequencingMid-fetal developmentAdditional risk genesHigh-confidence risk genesParent-child triosGene OntologyCell signalingExpression patternsCalcium ion transportFunctional convergenceCell cycleDamaging variantsGenesDNA sequencingDe novoASD probandsGenetic etiologyBiological mechanismsSequencingDNANetwork analysisIon transport
2021
Engineering spatial-organized cardiac organoids for developmental toxicity testing
Hoang P, Kowalczewski A, Sun S, Winston TS, Archilla AM, Lemus SM, Ercan-Sencicek AG, Gupta AR, Liu W, Kontaridis MI, Amack JD, Ma Z. Engineering spatial-organized cardiac organoids for developmental toxicity testing. Stem Cell Reports 2021, 16: 1228-1244. PMID: 33891865, PMCID: PMC8185451, DOI: 10.1016/j.stemcr.2021.03.013.Peer-Reviewed Original Research
2015
The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment
Cotney J, Muhle RA, Sanders SJ, Liu L, Willsey AJ, Niu W, Liu W, Klei L, Lei J, Yin J, Reilly SK, Tebbenkamp AT, Bichsel C, Pletikos M, Sestan N, Roeder K, State MW, Devlin B, Noonan JP. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nature Communications 2015, 6: 6404. PMID: 25752243, PMCID: PMC4355952, DOI: 10.1038/ncomms7404.Peer-Reviewed Original ResearchConceptsASD risk genesRisk genesRegulatory networksAncient gene regulatory networksHuman neural stem cellsLoss of CHD8Specific regulatory networksGene regulatory networksCo-expression networkAutism risk genesEmbryonic mouse cortexChromatin modifiersIdentification of recurrentChromodomain-HelicaseChd8 knockdownNeural stem cellsMouse neurodevelopmentCHD8Human brain developmentFunction mutationsGenesStem cellsHuman neurodevelopmentNovo lossBrain development
2013
Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism
Willsey AJ, Sanders SJ, Li M, Dong S, Tebbenkamp AT, Muhle RA, Reilly SK, Lin L, Fertuzinhos S, Miller JA, Murtha MT, Bichsel C, Niu W, Cotney J, Ercan-Sencicek AG, Gockley J, Gupta AR, Han W, He X, Hoffman EJ, Klei L, Lei J, Liu W, Liu L, Lu C, Xu X, Zhu Y, Mane SM, Lein ES, Wei L, Noonan JP, Roeder K, Devlin B, Sestan N, State MW. Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism. Cell 2013, 155: 997-1007. PMID: 24267886, PMCID: PMC3995413, DOI: 10.1016/j.cell.2013.10.020.Peer-Reviewed Original ResearchConceptsCoexpression networkASD genesComplex developmental syndromeGenome-wide sequencingCortical projection neuronsHigh-confidence ASD genesExpression data setsPleiotropic genesSpecific genesDevelopmental processesDevelopmental syndromesSequencing studiesGenesProjection neuronsCell typesBrain regionsType mutationsCommon phenotypeASD pathophysiologyPathogenesis of autismAutism spectrum disorderMutationsHuman brain regionsUnknown etiologyRecent studiesRare Nonconservative LRP6 Mutations Are Associated with Metabolic Syndrome
Singh R, Smith E, Fathzadeh M, Liu W, Go G, Subrahmanyan L, Faramarzi S, McKenna W, Mani A. Rare Nonconservative LRP6 Mutations Are Associated with Metabolic Syndrome. Human Mutation 2013, 34: 1221-1225. PMID: 23703864, PMCID: PMC3745535, DOI: 10.1002/humu.22360.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCase-Control StudiesCoronary DiseaseEuropeFemaleGenetic Predisposition to DiseaseGenetic VariationGlycosylationHumansLow Density Lipoprotein Receptor-Related Protein-6MaleMetabolic SyndromeMiddle AgedMutationPedigreePhylogenySequence AlignmentUnited StatesWnt ProteinsYoung AdultConceptsCoronary artery diseaseMetabolic syndromeLRP6 mutationFamilial coronary artery diseaseArtery diseaseDisease populationSyndromeConserved glycosylation siteNovel mutationsFunction mutationsPropeller domainRare mutationsEuropean controlsLRP6MutationsCritical roleMetabolic traitsWhite AmericansPrevalenceDisease
2012
Low Density Lipoprotein (LDL) Receptor-related Protein 6 (LRP6) Regulates Body Fat and Glucose Homeostasis by Modulating Nutrient Sensing Pathways and Mitochondrial Energy Expenditure*
Liu W, Singh R, Choi CS, Lee HY, Keramati AR, Samuel VT, Lifton RP, Shulman GI, Mani A. Low Density Lipoprotein (LDL) Receptor-related Protein 6 (LRP6) Regulates Body Fat and Glucose Homeostasis by Modulating Nutrient Sensing Pathways and Mitochondrial Energy Expenditure*. Journal Of Biological Chemistry 2012, 287: 7213-7223. PMID: 22232553, PMCID: PMC3293520, DOI: 10.1074/jbc.m111.286724.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, BrownAdiposityAllelesAnimalsDiabetes Mellitus, Type 2Dietary FatsEnergy MetabolismForkhead Box Protein O1Forkhead Transcription FactorsGluconeogenesisGlucoseGlucose-6-PhosphataseHomeostasisInsulin ResistanceLow Density Lipoprotein Receptor-Related Protein-6Mechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMitochondriaMultiprotein ComplexesObesityProteinsReceptors, LeptinTOR Serine-Threonine KinasesWnt Signaling PathwayConceptsLow-density lipoprotein receptor-related protein 6Type 2 diabetesInsulin resistanceInsulin sensitivityBody fatAdipose tissue insulin sensitivityLipoprotein receptor-related protein 6Tissue insulin resistanceTissue insulin sensitivityDiet-induced obesityHigh-fat dietLeptin receptor expressionHepatic insulin sensitivityHepatic glucose outputWild-type littermatesFoxo1-dependent expressionMitochondrial energy expenditureMetabolic syndromeFat dietReduced adiposityReceptor expressionPharmacological interventionsGlucose outputGlucose homeostasisKey gluconeogenic enzymes
2011
LRP6 Protein Regulates Low Density Lipoprotein (LDL) Receptor-mediated LDL Uptake*
Ye ZJ, Go GW, Singh R, Liu W, Keramati AR, Mani A. LRP6 Protein Regulates Low Density Lipoprotein (LDL) Receptor-mediated LDL Uptake*. Journal Of Biological Chemistry 2011, 287: 1335-1344. PMID: 22128165, PMCID: PMC3256876, DOI: 10.1074/jbc.m111.295287.Peer-Reviewed Original ResearchConceptsLDL uptakeLDL bindingHigh serum LDL cholesterol levelReceptor-mediated LDL uptakeSerum LDL cholesterol levelsSerum LDL levelsHigh serum LDL levelsLDL cholesterol levelsPeripheral B lymphocytesLDL levelsCholesterol levelsLDL clearanceLRP6 knockdownMutation carriersImpaired functionB lymphocytesLDL receptorLRP6 geneCHO cellsCritical modulatorLDLRLDL endocytosisGreater declineCHO-K1 cellsLRP6
2010
W15 THE ANTIPROLIFERATIVE EFFECT OF LRP6 AND ITS IMPAIRMENT BY R611C MUTATION ARE MEDIATED BY INDEPENDENT INTERMEDIATES OF THE PDGF PATHWAY
Keramati A, Singh R, Liu W, Faramarzi S, Nottoli T, Tellides G, Mani A. W15 THE ANTIPROLIFERATIVE EFFECT OF LRP6 AND ITS IMPAIRMENT BY R611C MUTATION ARE MEDIATED BY INDEPENDENT INTERMEDIATES OF THE PDGF PATHWAY. Atherosclerosis Plus 2010, 11: 4. DOI: 10.1016/s1567-5688(10)70016-7.Peer-Reviewed Original Research
2008
Mutation in EGFP Domain of LDL Receptor-Related Protein 6 Impairs Cellular LDL Clearance
Liu W, Mani S, Davis NR, Sarrafzadegan N, Kavathas PB, Mani A. Mutation in EGFP Domain of LDL Receptor-Related Protein 6 Impairs Cellular LDL Clearance. Circulation Research 2008, 103: 1280-1288. PMID: 18948618, PMCID: PMC3426315, DOI: 10.1161/circresaha.108.183863.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SubstitutionAnimalsApolipoproteins BB-LymphocytesCell LineCell MembraneEndosomesGene Expression RegulationGenetic Carrier ScreeningGreen Fluorescent ProteinsHumansImmunohistochemistryLDL-Receptor Related ProteinsLipoproteins, LDLLow Density Lipoprotein Receptor-Related Protein-6LysosomesMetabolic Clearance RateMiceMice, KnockoutMicroscopy, FluorescenceMutationConceptsLDL clearanceMutation carriersWild-type receptorEarly-onset atherosclerosisLow-density lipoprotein uptakeWild-type littermatesLymphoblastoid cellsSplenic B cellsTotal LRP6LDL receptor-related protein 6Unaffected family membersApolipoprotein BLRP6 expressionMembrane expression levelsB cellsLipoprotein uptakeLDL uptakeCholesterol uptakeLDL receptorLow efficacyPlasma membrane expression levelsReceptorsLDL endocytosisMembrane expressionProtein 6