2024
Review: Child Psychiatry in the Era of Genomics: The Promise of Translational Genetics Research for the Clinic
Fitzpatrick S, Antony I, Nurmi E, Fernandez T, Chung W, Brownstein C, Gonzalez-Heydrich J, Gur R, Merner A, Lázaro-Muñoz G, State M, Simon K, Hoffman E. Review: Child Psychiatry in the Era of Genomics: The Promise of Translational Genetics Research for the Clinic. JAACAP Open 2024 DOI: 10.1016/j.jaacop.2024.06.002.Peer-Reviewed Original ResearchGenetic testingHigh-confidence risk genesPsychiatric geneticsApproaches to gene discoveryGenetic researchTranslational genetic researchClinical genetic testingEra of genomicsWhole-exome sequencingChild psychiatric disordersGenetic architectureGene discoveryClinical evaluationPharmacogenetic testingExome sequencingRisk genesGenetic underpinningsGenetic findingsEarly-onset psychosisPsychiatric disordersGenetic conceptsGeneticsLack of familiarityClinical practiceObsessive-compulsive disorder
2023
High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways
Mendes H, Neelakantan U, Liu Y, Fitzpatrick S, Chen T, Wu W, Pruitt A, Jin D, Jamadagni P, Carlson M, Lacadie C, Enriquez K, Li N, Zhao D, Ijaz S, Sakai C, Szi C, Rooney B, Ghosh M, Nwabudike I, Gorodezky A, Chowdhury S, Zaheer M, McLaughlin S, Fernandez J, Wu J, Eilbott J, Vander Wyk B, Rihel J, Papademetris X, Wang Z, Hoffman E. High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways. Cell Reports 2023, 42: 112243. PMID: 36933215, PMCID: PMC10277173, DOI: 10.1016/j.celrep.2023.112243.Peer-Reviewed Original ResearchConceptsGene lossFunctional analysisHigh-throughput functional analysisZebrafish mutantsGene discoverySelect mutantsASD genesAutism genesKey pathwaysASD biologyBrain size differencesMutantsGenesSize differencesPathwayGlobal increaseRelevant mechanismsBiologyCentral challengeNeuroimmune dysfunctionRegionFunctionDiscoveryAutism spectrum disorder
2021
Signaling Pathways and Sex Differential Processes in Autism Spectrum Disorder
Enriquez KD, Gupta AR, Hoffman EJ. Signaling Pathways and Sex Differential Processes in Autism Spectrum Disorder. Frontiers In Psychiatry 2021, 12: 716673. PMID: 34690830, PMCID: PMC8531220, DOI: 10.3389/fpsyt.2021.716673.Peer-Reviewed Original ResearchASD genetic studiesBiological pathwaysGenetic studiesRisk gene discoveryCellular pathways downstreamASD risk genesWhole-exome sequencing studiesCommon biological pathwaysGene discoveryPathways downstreamGene expressionSequencing studiesRisk genesMale biasPathwayGenesNeuronal communicationCommon pathwayPotential roleFemale protective effectNeurodevelopmental disordersRecent analysisTranscriptomicsGenomicsRecent investigationsPTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets
DeSpenza T, Carlson M, Panchagnula S, Robert S, Duy PQ, Mermin-Bunnell N, Reeves BC, Kundishora A, Elsamadicy AA, Smith H, Ocken J, Alper SL, Jin SC, Hoffman EJ, Kahle KT. PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets. Trends In Neurosciences 2021, 44: 961-976. PMID: 34625286, PMCID: PMC8692171, DOI: 10.1016/j.tins.2021.08.007.Peer-Reviewed Original ResearchConceptsDevelopmental pleiotropyPTEN-PI3KMTOR pathwayMolecular pathophysiologyPTEN mutationsMolecular similarityTherapeutic targetCommon underlying mechanismNeurodevelopmental disordersUnderlying mechanismTherapeutic promisePleiotropyBiologyPhenotypicMutationsLimited understandingPathwayCommon neurodevelopmental disorderAutism spectrum disorderSimilarityTargetA simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes
Kroll F, Powell GT, Ghosh M, Gestri G, Antinucci P, Hearn TJ, Tunbak H, Lim S, Dennis HW, Fernandez JM, Whitmore D, Dreosti E, Wilson SW, Hoffman EJ, Rihel J. A simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes. ELife 2021, 10: e59683. PMID: 33416493, PMCID: PMC7793621, DOI: 10.7554/elife.59683.Peer-Reviewed Original ResearchConceptsKnockout methodComplex mutant phenotypesLarge genetic screenRapid genetic screeningGenetic screenMutant phenotypeEffective CRISPRBiallelic knockoutMolecular rhythmsHuman genesInjected embryosCircadian clockLarval zebrafishBehavioral phenotypesMultiple genesComplex phenotypesCurrent CRISPRTriple knockoutAttractive modelGenesGenetic contributionZebrafishPhenotypeKnockoutCRISPR
2020
Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus
Jin SC, Dong W, Kundishora AJ, Panchagnula S, Moreno-De-Luca A, Furey CG, Allocco AA, Walker RL, Nelson-Williams C, Smith H, Dunbar A, Conine S, Lu Q, Zeng X, Sierant MC, Knight JR, Sullivan W, Duy PQ, DeSpenza T, Reeves BC, Karimy JK, Marlier A, Castaldi C, Tikhonova IR, Li B, Peña HP, Broach JR, Kabachelor EM, Ssenyonga P, Hehnly C, Ge L, Keren B, Timberlake AT, Goto J, Mangano FT, Johnston JM, Butler WE, Warf BC, Smith ER, Schiff SJ, Limbrick DD, Heuer G, Jackson EM, Iskandar BJ, Mane S, Haider S, Guclu B, Bayri Y, Sahin Y, Duncan CC, Apuzzo MLJ, DiLuna ML, Hoffman EJ, Sestan N, Ment LR, Alper SL, Bilguvar K, Geschwind DH, Günel M, Lifton RP, Kahle KT. Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus. Nature Medicine 2020, 26: 1754-1765. PMID: 33077954, PMCID: PMC7871900, DOI: 10.1038/s41591-020-1090-2.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusPoor neurodevelopmental outcomesPost-surgical patientsCerebrospinal fluid accumulationNeural stem cell biologyGenetic disruptionWhole-exome sequencingPrimary pathomechanismEarly brain developmentNeurodevelopmental outcomesHigh morbidityCSF diversionMutation burdenFluid accumulationBrain ventriclesCH casesBrain developmentDe novo mutationsPatientsExome sequencingCSF dynamicsDisease mechanismsHydrocephalusNovo mutationsCell typesChapter 26 Modeling autism spectrum disorders in zebrafish
Dreosti E, Hoffman E, Rihel J. Chapter 26 Modeling autism spectrum disorders in zebrafish. 2020, 451-480. DOI: 10.1016/b978-0-12-817528-6.00026-7.ChaptersZebrafish modelGenetics of ASDGenome-wide association studiesHundreds of genesNervous system formComplex behavioral repertoireHuman neurodevelopmental disordersWhole-genome sequencingExcellent systemGenetic informationGenome sequencingAssociation studiesGenerate mutationsZebrafishUnique human traitsHuman traitsHuman biologyNeurodevelopmental disordersASD biologyGenetic alterationsRapid discoveryGenesBiologyBehavioral repertoireNeuronal processes
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
Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future
Sakai C, Ijaz S, Hoffman EJ. Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future. Frontiers In Molecular Neuroscience 2018, 11: 294. PMID: 30210288, PMCID: PMC6123572, DOI: 10.3389/fnmol.2018.00294.Peer-Reviewed Original ResearchGene functionZebrafish modelCRISPR/Cas9 geneSmall-molecule suppressorTransparent embryosZebrafish systemHigh-throughput pharmacological screensNeurodevelopmental disordersGenetic manipulationCas9 geneBehavioral phenotypesLarge progenyFunctional analysisLarval stagesPharmacological screensZebrafishRisk genesGenesModel systemExternal developmentPhenotypeCircuit-level mechanismsBasic mechanismsNeural circuitsNervous system
2017
Assessing Risk: Gene Discovery
Fernandez TV, Gupta AR, Hoffman EJ. Assessing Risk: Gene Discovery. In Lewis’s Child and Adolescent Psychiatry: A Comprehensive Textbook, 5th Edition, Eds. Martin, A, Bloch, MH, Volkmar FR. Philadelphia: Wolters Kluwers, 2017.Chapters
2016
20.0 Molecular and Genetic Mechanisms in Autism Spectrum Disorder: From Bench to Bedside
Hoffman E, State M. 20.0 Molecular and Genetic Mechanisms in Autism Spectrum Disorder: From Bench to Bedside. Journal Of The American Academy Of Child & Adolescent Psychiatry 2016, 55: s288. DOI: 10.1016/j.jaac.2016.07.231.Peer-Reviewed Original Research20.3 ZEBRAFISH MODELS OF AUTISM-RISK GENES AS A PATH TOWARD DRUG DISCOVERY
Hoffman E. 20.3 ZEBRAFISH MODELS OF AUTISM-RISK GENES AS A PATH TOWARD DRUG DISCOVERY. Journal Of The American Academy Of Child & Adolescent Psychiatry 2016, 55: s289. DOI: 10.1016/j.jaac.2016.07.234.Peer-Reviewed Original ResearchZebrafish: A Translational Model System for Studying Neuropsychiatric Disorders
Ijaz S, Hoffman EJ. Zebrafish: A Translational Model System for Studying Neuropsychiatric Disorders. Journal Of The American Academy Of Child & Adolescent Psychiatry 2016, 55: 746-748. PMID: 27566113, PMCID: PMC5521170, DOI: 10.1016/j.jaac.2016.06.008.Peer-Reviewed Original ResearchEstrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2
Hoffman EJ, Turner KJ, Fernandez JM, Cifuentes D, Ghosh M, Ijaz S, Jain RA, Kubo F, Bill BR, Baier H, Granato M, Barresi MJ, Wilson SW, Rihel J, State MW, Giraldez AJ. Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2. Neuron 2016, 89: 725-733. PMID: 26833134, PMCID: PMC4766582, DOI: 10.1016/j.neuron.2015.12.039.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedAutistic DisorderDisease Models, AnimalEstrogensGene Expression RegulationGenisteinGreen Fluorescent ProteinsHumansLarvaLuminescent ProteinsMembrane ProteinsMotor ActivityMutationNerve Tissue ProteinsPhenotypePhytoestrogensPsychotropic DrugsSeizuresSleep-Wake Transition DisordersVesicular Glutamate Transport Protein 2Zebrafish
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 studies
2010
Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA)
Sander JD, Dahlborg EJ, Goodwin MJ, Cade L, Zhang F, Cifuentes D, Curtin SJ, Blackburn JS, Thibodeau-Beganny S, Qi Y, Pierick CJ, Hoffman E, Maeder ML, Khayter C, Reyon D, Dobbs D, Langenau DM, Stupar RM, Giraldez AJ, Voytas DF, Peterson RT, Yeh JR, Joung JK. Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nature Methods 2010, 8: 67-69. PMID: 21151135, PMCID: PMC3018472, DOI: 10.1038/nmeth.1542.Peer-Reviewed Original ResearchProgress in Cytogenetics: Implications for Child Psychopathology
Hoffman EJ, State MW. Progress in Cytogenetics: Implications for Child Psychopathology. Journal Of The American Academy Of Child & Adolescent Psychiatry 2010, 49: 736-751. PMID: 20643309, DOI: 10.1016/j.jaac.2010.03.016.Peer-Reviewed Original ResearchConceptsChromosomal structureHuman genetic variationSequence of DNAChromosomal variationMicroarray-based detectionGenetic variationGenetic basisMolecular cytogeneticsGenetic underpinningsMicroarray technologySynapse functionKey discoveriesStructural variationsRecent findingsUnaffected individualsChromosomal studiesCytogenetic investigationsDevelopmental neuropsychiatric disordersCytogeneticsLight microscopyChromosomesGeneticsDNADramatic increasePhenotype
2008
Effects of ethanol on axon outgrowth and branching in developing rat cortical neurons.
Hoffman EJ, Mintz CD, Wang S, McNickle DG, Salton SR, Benson DL. Effects of ethanol on axon outgrowth and branching in developing rat cortical neurons. Neuroscience 2008, 157: 556-65. PMID: 18926887, PMCID: PMC2626542, DOI: 10.1016/j.neuroscience.2008.08.071.Peer-Reviewed Original ResearchMultiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: Efficient identification of known microduplications and identification of a novel microduplication in ASMT
Cai G, Edelmann L, Goldsmith JE, Cohen N, Nakamine A, Reichert JG, Hoffman EJ, Zurawiecki DM, Silverman JM, Hollander E, Soorya L, Anagnostou E, Betancur C, Buxbaum JD. Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: Efficient identification of known microduplications and identification of a novel microduplication in ASMT. BMC Medical Genomics 2008, 1: 50. PMID: 18925931, PMCID: PMC2588447, DOI: 10.1186/1755-8794-1-50.Peer-Reviewed Original ResearchA large‐scale screen for coding variants in SERT/SLC6A4 in autism spectrum disorders
Sakurai T, Reichert J, Hoffman EJ, Cai G, Jones HB, Faham M, Buxbaum JD. A large‐scale screen for coding variants in SERT/SLC6A4 in autism spectrum disorders. Autism Research 2008, 1: 251-257. PMID: 19360675, PMCID: PMC2678895, DOI: 10.1002/aur.30.Peer-Reviewed Original Research