Featured Publications
Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration
Bilguvar K, Tyagi NK, Ozkara C, Tuysuz B, Bakircioglu M, Choi M, Delil S, Caglayan AO, Baranoski JF, Erturk O, Yalcinkaya C, Karacorlu M, Dincer A, Johnson MH, Mane S, Chandra SS, Louvi A, Boggon TJ, Lifton RP, Horwich AL, Gunel M. Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3489-3494. PMID: 23359680, PMCID: PMC3587195, DOI: 10.1073/pnas.1222732110.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge of OnsetAmino Acid SequenceBase SequenceChild, PreschoolExomeFemaleGenes, RecessiveHomozygoteHumansHydrolysisMaleModels, MolecularMolecular Sequence DataMutation, MissenseNerve DegenerationNeuronsPedigreeProtein BindingSequence Analysis, DNASubstrate SpecificitySyndromeThermodynamicsUbiquitinUbiquitin ThiolesteraseConceptsUbiquitin C-terminal hydrolase L1Upper motor neuron dysfunctionMotor neuron dysfunctionProgressive neurodegenerative syndromeEarly-onset progressive neurodegenerationChildhood-onset blindnessWhole-exome sequencingNeuron dysfunctionHomozygous missense mutationIndex caseNervous systemProgressive neurodegenerationNeurodegenerative syndromeCerebellar ataxiaHydrolase activityNear complete lossComplete lossAffected individualsConsanguineous unionsMissense mutationsRecessive lossHomozygosity mappingProper positioningReduced affinitySpasticity
2016
Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly
Jerber J, Zaki MS, Al-Aama JY, Rosti RO, Ben-Omran T, Dikoglu E, Silhavy JL, Caglar C, Musaev D, Albrecht B, Campbell KP, Willer T, Almuriekhi M, Çağlayan A, Vajsar J, Bilgüvar K, Ogur G, Jamra R, Günel M, Gleeson JG. Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly. American Journal Of Human Genetics 2016, 99: 1181-1189. PMID: 27773428, PMCID: PMC5097947, DOI: 10.1016/j.ajhg.2016.09.007.Peer-Reviewed Original ResearchConceptsCongenital muscular dystrophyCobblestone lissencephalyOvermigration of neuronsBiallelic mutationsMuscular dystrophyTMTC3Affected individualsWalker-Warburg syndromeMembrane componentsSevere brain malformationsBasement membrane componentsFukuyama congenital muscular dystrophyMuscle creatine phosphokinaseEye defectsMutationsGenesRecessive formGenetic disordersGlial cellsMinimal eyeMuscle involvementCortical dysplasiaBrain malformationsEye anomaliesCreatine phosphokinase
2015
Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand–receptor interactions
Reshetnyak AV, Murray PB, Shi X, Mo ES, Mohanty J, Tome F, Bai H, Gunel M, Lax I, Schlessinger J. Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand–receptor interactions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 15862-15867. PMID: 26630010, PMCID: PMC4702955, DOI: 10.1073/pnas.1520099112.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnaplastic Lymphoma KinaseAnimalsCell LineCell Line, TumorCell ProliferationCytokinesDoxycyclineEnzyme ActivationHEK293 CellsHeparinHumansImmunoblottingLigandsMiceMolecular Sequence DataNIH 3T3 CellsProtein BindingReceptor Protein-Tyrosine KinasesSequence Homology, Amino AcidConceptsLeukocyte tyrosine kinaseReceptor tyrosine kinasesTyrosine kinaseIL-3-independent growthCritical cellular functionsBa/F3 cellsCell surface receptorsAnaplastic lymphoma kinaseLigand-receptor interactionsCellular functionsLigand bindingF3 cellsReceptor tyrosineProtein ligandsNIH/3T3 cellsKinaseSurface receptorsIndependent growthSubnanomolar potencyCellsDisease statesHigh affinityLymphoma kinaseFAM150ANovel cytokine
2014
Paediatric hepatocellular carcinoma due to somatic CTNNB1 and NFE2L2 mutations in the setting of inherited bi-allelic ABCB11 mutations
Vilarinho S, Erson-Omay EZ, Harmanci AS, Morotti R, Carrion-Grant G, Baranoski J, Knisely AS, Ekong U, Emre S, Yasuno K, Bilguvar K, Günel M. Paediatric hepatocellular carcinoma due to somatic CTNNB1 and NFE2L2 mutations in the setting of inherited bi-allelic ABCB11 mutations. Journal Of Hepatology 2014, 61: 1178-1183. PMID: 25016225, DOI: 10.1016/j.jhep.2014.07.003.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceATP Binding Cassette Transporter, Subfamily B, Member 11ATP-Binding Cassette TransportersBase SequenceBeta CateninCarcinoma, HepatocellularCholestasis, IntrahepaticDNA, NeoplasmFemaleGerm-Line MutationHumansInfantLiver NeoplasmsMolecular Sequence DataMutationMutation, MissenseNF-E2-Related Factor 2Sequence Homology, Amino AcidConceptsBile salt export pumpWhole-exome sequencingHepatocellular carcinomaMonths of ageNFE2L2 mutationsABCB11 mutationsSomatic CTNNB1Background liver parenchymaPediatric hepatocellular carcinomaNew onsetSomatic driver mutationsBSEP expressionLiver parenchymaHCC tissuesHepatocellular carcinogenesisWES analysisExport pumpDriver mutationsCTNNB1 mutationsExome sequencingChild's diagnosisClonality analysisGermline DNAPossible genetic basisEarly childhood
2012
Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion
Emre Onat O, Gulsuner S, Bilguvar K, Nazli Basak A, Topaloglu H, Tan M, Tan U, Gunel M, Ozcelik T. Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion. European Journal Of Human Genetics 2012, 21: 281-285. PMID: 22892528, PMCID: PMC3573203, DOI: 10.1038/ejhg.2012.170.Peer-Reviewed Original ResearchConceptsC-terminal transmembrane regionATPase domainNext-generation sequencingTransmembrane regionHomozygous regionsHomozygosity mappingAffected individualsATP8A2Novel missense variantChromosome 13q12Missense mutationsATP8A2 geneSegregation analysisConsanguineous familyMissense variantsUnrelated individualsMutationsMental retardationQuadrupedal locomotionGenesDysequilibrium syndromeSequencingTranslocationATPaseNovo
2004
The AHNAKs are a class of giant propeller-like proteins that associate with calcium channel proteins of cardiomyocytes and other cells
Komuro A, Masuda Y, Kobayashi K, Babbitt R, Gunel M, Flavell RA, Marchesi VT. The AHNAKs are a class of giant propeller-like proteins that associate with calcium channel proteins of cardiomyocytes and other cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 4053-4058. PMID: 15007166, PMCID: PMC384694, DOI: 10.1073/pnas.0308619101.Peer-Reviewed Original Research
2002
KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein
Gunel M, Laurans MS, Shin D, DiLuna ML, Voorhees J, Choate K, Nelson-Williams C, Lifton RP. KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 10677-10682. PMID: 12140362, PMCID: PMC125011, DOI: 10.1073/pnas.122354499.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAortaCattleCells, CulturedCentral Nervous System Vascular MalformationsChlorocebus aethiopsCOS CellsEndothelium, VascularGene ExpressionMicrotubule-Associated ProteinsMicrotubulesMitosisMolecular Sequence DataMutagenesisPrecipitin TestsProto-Oncogene ProteinsRadiographyTubulinConceptsCerebral cavernous malformationsCavernous malformationsCerebral cavernous malformation lesionsMicrotubule-associated proteinsProtein-1 alphaAutosomal dominant diseaseEndothelial tube formationCerebral hemorrhageCerebral capillariesEndothelial cellsDominant diseaseMalformationsTube formationPlus endsSite of cytokinesisSpindle pole bodyEvidence of interactionGene 1Possible roleCell-matrix interactionsKRIT1Late phaseEnds of microtubulesEndothelial cell shapePole body
2001
Human Hypertension Caused by Mutations in WNK Kinases
Wilson F, Disse-Nicodème S, Choate K, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford D, Lipkin G, Achard J, Feely M, Dussol B, Berland Y, Unwin R, Mayan H, Simon D, Farfel Z, Jeunemaitre X, Lifton R. Human Hypertension Caused by Mutations in WNK Kinases. Science 2001, 293: 1107-1112. PMID: 11498583, DOI: 10.1126/science.1062844.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceChromosome MappingChromosomes, Human, Pair 12Chromosomes, Human, Pair 17CytoplasmFemaleGene Expression Regulation, EnzymologicGenetic LinkageHumansHypertensionIntercellular JunctionsIntracellular Signaling Peptides and ProteinsIntronsKidney Tubules, CollectingKidney Tubules, DistalMaleMembrane ProteinsMicroscopy, FluorescenceMinor Histocompatibility AntigensMolecular Sequence DataMutationMutation, MissensePedigreePhosphoproteinsProtein Serine-Threonine KinasesPseudohypoaldosteronismSequence DeletionSignal TransductionWNK Lysine-Deficient Protein Kinase 1Zonula Occludens-1 ProteinConceptsMajor public health problemPublic health problemRenal salt reabsorptionAntihypertensive drugsHuman hypertensionUnknown causeDistal nephronKidney segmentsPseudohypoaldosteronism type IIHealth problemsSalt reabsorptionHypertensionWNK1 expressionNew targetsWNK kinasesTight junctionsType IISerine-threonine kinaseIntronic deletionWNK4WNK familyMutationsWNK1KinaseExcretion