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
A neurogenetic analysis of female autism
Jack A, Sullivan CAW, Aylward E, Bookheimer SY, Dapretto M, Gaab N, Van Horn JD, Eilbott J, Jacokes Z, Torgerson CM, Bernier RA, Geschwind DH, McPartland JC, Nelson CA, Webb SJ, Pelphrey KA, Gupta AR, Bernier R, McPartland J, Ventola P, Kresse A, Neuhaus E, Corrigan S, Wolf J, McDonald N, Ankenman K, Webb S, Jeste S, Nelson C, Naples A, Libsack E, Pelphrey K, Aylward E, Bookheimer S, Gaab N, Dapretto M, Van Horn J, Jack A, Guilford D, Torgerson C, Welker O, Geschwind D, Gupta A, Sullivan C, Lowe J, Jacokes Z, MacDonnell E, Tsapelas H, Depedro-Mercier D, Keifer C, Ventola P. A neurogenetic analysis of female autism. Brain 2021, 144: 1911-1926. PMID: 33860292, PMCID: PMC8320285, DOI: 10.1093/brain/awab064.Peer-Reviewed Original ResearchLanguage and Aggressive Behaviors in Male and Female Youth with Autism Spectrum Disorder
Neuhaus E, Kang VY, Kresse A, Corrigan S, Aylward E, Bernier R, Bookheimer S, Dapretto M, Jack A, Jeste S, McPartland JC, Van Horn JD, Pelphrey K, Webb SJ. Language and Aggressive Behaviors in Male and Female Youth with Autism Spectrum Disorder. Journal Of Autism And Developmental Disorders 2021, 52: 454-462. PMID: 33682042, PMCID: PMC9407024, DOI: 10.1007/s10803-020-04773-0.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSpectrum disorderChild/family factorsAggressive behaviorSocial-emotional difficultiesCommunication skillsPattern of resultsTypical developmentBroader contextual factorsFamily factorsDisruptive behaviorSevere aggressionAggressionFemale youthFamily characteristicsIntervention methodsContextual factorsImportant correlatesLow family incomeYouthSkillsFamily incomeDisordersDifficultiesBehavior
2020
Do Biological Sex and Early Developmental Milestones Predict the Age of First Concerns and Eventual Diagnosis in Autism Spectrum Disorder?
Harrop C, Libsack E, Bernier R, Dapretto M, Jack A, McPartland JC, Van Horn JD, Webb SJ, Pelphrey K, Consortium T. Do Biological Sex and Early Developmental Milestones Predict the Age of First Concerns and Eventual Diagnosis in Autism Spectrum Disorder? Autism Research 2020, 14: 156-168. PMID: 33274604, PMCID: PMC8023413, DOI: 10.1002/aur.2446.Peer-Reviewed Original ResearchConceptsDevelopmental milestonesBiological sexAutism spectrum disorder diagnosisAutism spectrum disorderEarly developmental milestonesSex differencesStrongest predictorTypical developmentASD diagnosisFirst wordSpectrum disorderLower IQFirst concernsAge parentsDisorder diagnosisIQASDSignificant predictorsParentsInitial concernsChildrenPredictorsLater ageTiming of diagnosisInter-individual variationNeural responsivity to social rewards in autistic female youth
Lawrence KE, Hernandez LM, Eilbott J, Jack A, Aylward E, Gaab N, Van Horn JD, Bernier RA, Geschwind DH, McPartland JC, Nelson CA, Webb SJ, Pelphrey KA, Bookheimer SY, Dapretto M. Neural responsivity to social rewards in autistic female youth. Translational Psychiatry 2020, 10: 178. PMID: 32488083, PMCID: PMC7266816, DOI: 10.1038/s41398-020-0824-8.Peer-Reviewed Original ResearchConceptsImplicit learning taskSocial rewardsAutistic girlsAutistic boysLearning taskSocial reward processingSocial reward systemFemale youthPrevious neuroimaging studiesFunctional magnetic resonanceLateral frontal cortexSocial stimuliNeural responsivityReward processingSocial motivationRewarding stimuliAnterior insulaGreater activityNeural activationNeuroimaging studiesPotential sex differencesRewarding natureSalience detectionAutistic femalesBehavioral evidenceIdentification of amygdala-expressed genes associated with autism spectrum disorder
Herrero MJ, Velmeshev D, Hernandez-Pineda D, Sethi S, Sorrells S, Banerjee P, Sullivan C, Gupta AR, Kriegstein AR, Corbin JG. Identification of amygdala-expressed genes associated with autism spectrum disorder. Molecular Autism 2020, 11: 39. PMID: 32460837, PMCID: PMC7251751, DOI: 10.1186/s13229-020-00346-1.Peer-Reviewed Original ResearchConceptsASD susceptibility genesSusceptibility genesSingle-nucleus RNA-seq dataCohort of genesIdentification of hundredsRNA-seq dataCell-type specificityAvailable gene expression databasesGene expression analysisGene expression databaseSpecific cell typesEarly developmental stagesHuman tissuesSeq analysisGene sets
2019
De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette’s Disorder and Autism
Cappi C, Oliphant ME, Péter Z, Zai G, Conceição do Rosário M, Sullivan CAW, Gupta AR, Hoffman EJ, Virdee M, Olfson E, Abdallah SB, Willsey AJ, Shavitt RG, Miguel EC, Kennedy JL, Richter MA, Fernandez TV. De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette’s Disorder and Autism. Biological Psychiatry 2019, 87: 1035-1044. PMID: 31771860, PMCID: PMC7160031, DOI: 10.1016/j.biopsych.2019.09.029.Peer-Reviewed Original Research
2018
PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder
Goodrich M, Armour AC, Panchapakesan K, You X, Devaney J, Knoblach S, Sullivan CAW, Herrero MJ, Gupta AR, Vaidya CJ, Kenworthy L, Corbin JG. PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder. Autism Research 2018, 12: 200-211. PMID: 30556326, PMCID: PMC6665682, DOI: 10.1002/aur.2051.Peer-Reviewed Original ResearchConceptsResting-state functional connectivity differencesAutism spectrum disorderHuman amygdalaRight middle temporal gyrusFunctional connectivity differencesHigher functional connectivityEarly postnatal stagesNumerous neurodevelopmental disordersMiddle temporal gyrusGC genotypeBrain trajectoriesRisk genotypesSocial deficitsConnectivity differencesAmygdalaTemporal gyrusFunctional connectivityBrain connectivityPostnatal stagesTime pointsNeurodevelopmental disordersMiceCritical time pointsMultimodal approachPossible alterations
2017
Neurogenetic analysis of childhood disintegrative disorder
Gupta AR, Westphal A, Yang DYJ, Sullivan CAW, Eilbott J, Zaidi S, Voos A, Vander Wyk BC, Ventola P, Waqar Z, Fernandez TV, Ercan-Sencicek AG, Walker MF, Choi M, Schneider A, Hedderly T, Baird G, Friedman H, Cordeaux C, Ristow A, Shic F, Volkmar FR, Pelphrey KA. Neurogenetic analysis of childhood disintegrative disorder. Molecular Autism 2017, 8: 19. PMID: 28392909, PMCID: PMC5379515, DOI: 10.1186/s13229-017-0133-0.Peer-Reviewed Original ResearchAdaptor Proteins, Signal TransducingAutism Spectrum DisorderBasic Helix-Loop-Helix Transcription FactorsBrainBrain MappingCase-Control StudiesChildChild, PreschoolChromosomes, Human, XDisease ProgressionDNA Copy Number VariationsExome SequencingFemaleGene ExpressionHumansIntellectual DisabilityMagnetic Resonance ImagingMaleMaternal InheritanceNuclear ProteinsPhenotypePolymorphism, GeneticSeverity of Illness IndexSiblingsTranscription FactorsTranscriptomeThe scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2
Jeong J, VanHouten JN, Kim W, Dann P, Sullivan C, Choi J, Sneddon WB, Friedman PA, Wysolmerski JJ. The scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2. Journal Of Biological Chemistry 2017, 292: 6555-6568. PMID: 28235801, PMCID: PMC5399107, DOI: 10.1074/jbc.m116.770883.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnimalsApoptosisBreast NeoplasmsCalciumCell Line, TumorCell MembraneCell ProliferationFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansMiceMicroscopy, FluorescencePhosphoproteinsPlasma Membrane Calcium-Transporting ATPasesReceptor, ErbB-2RNA, MessengerSignal TransductionSodium-Hydrogen ExchangersConceptsBreast cancerHER2-positive breast cancerHER2-positive statusInvasive breast cancerHuman ductal carcinomaDegradation of HER2Normal mammary epithelial cellsMalignant breast cellsBreast cancer cellsErbB2/HER2Tyrosine kinase HER2Sodium-hydrogen exchanger regulatory factor-1Ductal carcinomaHER2 expressionExchanger regulatory factor 1Mammary epithelial cellsHER2Regulatory factor 1NHERF1 expressionBreast cellsEpithelial cellsCancerCancer cellsFactor 1PMCA2
2016
Calcium-Sensing Receptor Promotes Breast Cancer by Stimulating Intracrine Actions of Parathyroid Hormone–Related Protein
Kim W, Takyar FM, Swan K, Jeong J, VanHouten J, Sullivan C, Dann P, Yu H, Fiaschi-Taesch N, Chang W, Wysolmerski J. Calcium-Sensing Receptor Promotes Breast Cancer by Stimulating Intracrine Actions of Parathyroid Hormone–Related Protein. Cancer Research 2016, 76: 5348-5360. PMID: 27450451, PMCID: PMC5026591, DOI: 10.1158/0008-5472.can-15-2614.Peer-Reviewed Original ResearchConceptsMMTV-PyMT miceBreast cancer cellsCaSR activationBone metastasesBreast cancerInhibited tumor cell proliferationOsteolytic bone metastasesCancer cellsHuman breast cancer cell linesCalcium-sensing receptorHuman breast cancer cellsHormone-related proteinTransgenic mouse modelBreast cancer cell linesMMTV-PyMT transgenic mouse modelBreast cancer progressionTumor cell proliferationTumor cell growthCancer cell linesPTHrP levelsTissue-specific disruptionHigh extracellular concentrationsPTHrP productionCASR genePTHrP expressionPMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer
Jeong J, VanHouten JN, Dann P, Kim W, Sullivan C, Yu H, Liotta L, Espina V, Stern DF, Friedman PA, Wysolmerski JJ. PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e282-e290. PMID: 26729871, PMCID: PMC4725473, DOI: 10.1073/pnas.1516138113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCalciumCarcinogenesisCell Line, TumorCell MembraneCell ProliferationCell SurvivalEndocytosisFemaleFluorescent Antibody TechniqueForkhead Box Protein O1Forkhead Transcription FactorsGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansImmunoblottingIntracellular SpaceMammary Neoplasms, AnimalMicePlasma Membrane Calcium-Transporting ATPasesProtein BindingProtein TransportReceptor, ErbB-2Signal TransductionSurvival AnalysisConceptsBreast cancerHigh tumor levelsDegradation of HER2Increases Intracellular CalciumMouse mammary tumor virusBreast cancer cellsMammary tumor virusPMCA2 levelsNeu miceTumor levelsFormation of tumorsHER2 levelsIntracellular calciumTherapeutic targetBreast tumorsHER2Milk calciumExpression correlatesCancerHSP 90Mammary glandCancer cellsTumor virusTumorsCalcium
2015
Phase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin–bound paclitaxel in patients with advanced solid tumors
Abu-Khalaf MM, Baumgart MA, Gettinger SN, Doddamane I, Tuck DP, Hou S, Chen N, Sullivan C, Lezon-Geyda K, Zelterman D, Hatzis C, Deshpande H, Digiovanna MP, Azodi M, Schwartz PE, Harris LN. Phase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin–bound paclitaxel in patients with advanced solid tumors. Cancer 2015, 121: 1817-1826. PMID: 25649370, DOI: 10.1002/cncr.29254.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityIntravenous nab-paclitaxelPhase 1b studyAdvanced solid tumorsNab-paclitaxelFDG activityDay 1Solid tumorsNanoparticle albumin-bound paclitaxelMammalian targetWeekly oral doseAcceptable safety profileRapamycin inhibitor sirolimusAlbumin-bound paclitaxelClinical trial endpointsExploratory gene expression analysisPositron emission tomographyStable diseaseTaxane therapyPartial responseWeekly doseComplete responseOral sirolimusPharmacodynamic assessmentOral doseNo Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins
Murdoch JD, Gupta AR, Sanders SJ, Walker MF, Keaney J, Fernandez TV, Murtha MT, Anyanwu S, Ober GT, Raubeson MJ, DiLullo NM, Villa N, Waqar Z, Sullivan C, Gonzalez L, Willsey AJ, Choe SY, Neale BM, Daly MJ, State MW. No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins. PLOS Genetics 2015, 11: e1004852. PMID: 25621974, PMCID: PMC4306541, DOI: 10.1371/journal.pgen.1004852.Peer-Reviewed Original ResearchConceptsContactin-Associated ProteinSingle nucleotide variantsRelated gene familiesPoint mutationsLike-2Autism risk genesHeterozygous single-nucleotide variantsNumber variation analysisGene familyNext-generation sequencingSequence dataMolecular cytogeneticsRare point mutationsAssociation studiesHomozygosity mappingNucleotide variantsRisk genesRare heterozygous mutationsProteinHeterozygous point mutationMutationsGenesVariation analysisContactinHeterozygous mutations
2014
The contribution of de novo coding mutations to autism spectrum disorder
Iossifov I, O’Roak B, Sanders SJ, Ronemus M, Krumm N, Levy D, Stessman HA, Witherspoon KT, Vives L, Patterson KE, Smith JD, Paeper B, Nickerson DA, Dea J, Dong S, Gonzalez LE, Mandell JD, Mane SM, Murtha MT, Sullivan CA, Walker MF, Waqar Z, Wei L, Willsey AJ, Yamrom B, Lee YH, Grabowska E, Dalkic E, Wang Z, Marks S, Andrews P, Leotta A, Kendall J, Hakker I, Rosenbaum J, Ma B, Rodgers L, Troge J, Narzisi G, Yoon S, Schatz MC, Ye K, McCombie WR, Shendure J, Eichler EE, State MW, Wigler M. The contribution of de novo coding mutations to autism spectrum disorder. Nature 2014, 515: 216-221. PMID: 25363768, PMCID: PMC4313871, DOI: 10.1038/nature13908.Peer-Reviewed Original ResearchConceptsLGD mutationsMissense mutationsWild-type alleleChromatin modifiersGene-disrupting mutationsGenetic architectureCopy number variantsDe novo mutationsDe novo missense mutationsWhole-exome sequencingHuman diseasesGenesNovo missense mutationNumber variantsLikely gene-disrupting mutationsMutationsDe novoNovo mutationsExome sequencingSimplex familiesTargetFMRPPowerful toolSimilar numberSequencingDe Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder
Dong S, Walker MF, Carriero NJ, DiCola M, Willsey AJ, Ye AY, Waqar Z, Gonzalez LE, Overton JD, Frahm S, Keaney JF, Teran NA, Dea J, Mandell JD, Bal V, Sullivan CA, DiLullo NM, Khalil RO, Gockley J, Yuksel Z, Sertel SM, Ercan-Sencicek AG, Gupta AR, Mane SM, Sheldon M, Brooks AI, Roeder K, Devlin B, State MW, Wei L, Sanders SJ. De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder. Cell Reports 2014, 9: 16-23. PMID: 25284784, PMCID: PMC4194132, DOI: 10.1016/j.celrep.2014.08.068.Peer-Reviewed Original ResearchAutomated Quantitative Analysis of Tissue Microarray of 443 Patients with Colorectal Adenocarcinoma: Low Expression of Bcl-2 Predicts Poor Survival
Nicholson AD, Guo X, Sullivan CA, Cha CH. Automated Quantitative Analysis of Tissue Microarray of 443 Patients with Colorectal Adenocarcinoma: Low Expression of Bcl-2 Predicts Poor Survival. Journal Of The American College Of Surgeons 2014, 219: 977-987. PMID: 25127509, DOI: 10.1016/j.jamcollsurg.2014.07.007.Peer-Reviewed Original ResearchConceptsDisease-specific survivalBcl-2 expressionColorectal cancerOverall survivalPoor disease-specific survivalCox proportional hazards modelIndependent prognostic factorSubset of patientsColorectal adenocarcinoma samplesLog-rank testBcl-2Proportional hazards modelSemi-quantitative grading methodsColorectal cancer samplesNumber of cancersPrognostic factorsT stageChemotherapy choiceClinicopathologic variablesColorectal adenocarcinomaUnivariate analysisPatient outcomesPoor survivalTissue microarrayAggressive phenotypeA germline mutation in the BRCA13’UTR predicts Stage IV breast cancer
Dorairaj JJ, Salzman DW, Wall D, Rounds T, Preskill C, Sullivan C, Lindner R, Curran C, Lezon-Geyda K, McVeigh T, Harris L, Newell J, Kerin MJ, Wood M, Miller N, Weidhaas JB. A germline mutation in the BRCA13’UTR predicts Stage IV breast cancer. BMC Cancer 2014, 14: 421. PMID: 24915755, PMCID: PMC4059881, DOI: 10.1186/1471-2407-14-421.Peer-Reviewed Original ResearchConceptsStage IV breast cancerBreast cancerTumor biologyCancer riskBRCA1 gene expressionTriple-negative breast cancerLess dense breastsStage IV diseaseAggressive tumor biologyBreast cancer patientsBreast cancer riskOvarian cancer riskCohort of womenNegative breast cancerTriple-negative samplesBreast cancer cell linesBreast tumor tissuesHigh-risk familiesNegative patient samplesCancer cell linesObese womenGene expressionCancer patientsTT variantBreast program
2013
Molecular Phenotypes in Triple Negative Breast Cancer from African American Patients Suggest Targets for Therapy
Lindner R, Sullivan C, Offor O, Lezon-Geyda K, Halligan K, Fischbach N, Shah M, Bossuyt V, Schulz V, Tuck DP, Harris LN. Molecular Phenotypes in Triple Negative Breast Cancer from African American Patients Suggest Targets for Therapy. PLOS ONE 2013, 8: e71915. PMID: 24260093, PMCID: PMC3832509, DOI: 10.1371/journal.pone.0071915.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNegative breast cancerInsulin-like growth factor-1African American patientsAA patientsBreast cancerAmerican patientsAA tumorsHigher breast cancer mortalityLuminal androgen receptorBreast cancer mortalityDistinct transcriptional programsBasal-like subtypeBasal-like phenotypeGrowth factor-1Expression of VEGFHigher tumor vascularizationDrug response profilesEA tumorsRetrospective cohortTNBC patientsEA patientsPoor prognosisTNBC casesTNBC subtypes
2012
Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer
Neumeister VM, Sullivan CA, Lindner R, Lezon-Geyda K, Li J, Zavada J, Martel M, Glazer PM, Tuck DP, Rimm DL, Harris L. Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer. Breast Cancer Research And Treatment 2012, 136: 67-75. PMID: 22976806, DOI: 10.1007/s10549-012-2232-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, NeoplasmBiomarkers, TumorBRCA1 ProteinBreast NeoplasmsCarbonic Anhydrase IXCarbonic AnhydrasesCell HypoxiaFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedMutationNeoplasm StagingReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionConceptsTriple-negative breast cancerCA IX protein expressionNegative breast cancerBreast cancer cohortTNBC cohortProtein expressionBreast cancerCancer cohortCA IXTriple-negative patientsWorse overall survivalBreast cancer patientsTriple-negative phenotypePARP inhibitor therapyUnselected breast cancer cohortGene expression signaturesInhibitor therapyNegative patientsOverall survivalUnselected cohortCancer patientsBRCA1 protein expressionUseful biomarkerPatientsDefective homologous recombination