2023
Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatients
2022
De novo mutations in the BMP signaling pathway in lambdoid craniosynostosis
Timberlake AT, Kiziltug E, Jin SC, Nelson-Williams C, Loring E, Allocco A, Marlier A, Banka S, Stuart H, Passos-Buenos M, Rosa R, Rogatto S, Tonne E, Stiegler A, Boggon T, Alperovich M, Steinbacher D, Staffenberg D, Flores R, Persing J, Kahle K, Lifton R. De novo mutations in the BMP signaling pathway in lambdoid craniosynostosis. Human Genetics 2022, 142: 21-32. PMID: 35997807, DOI: 10.1007/s00439-022-02477-2.Peer-Reviewed Original ResearchConceptsDe novo mutationsDamaging de novo mutationsSingle-cell RNA sequencing analysisTranscriptional co-repressorTarget sequence recognitionRNA sequencing analysisTranscription factor NfixNovo mutationsEnrichment of mutationsBMP receptorsCo-repressorParent-offspring triosTranscription factorsGenetic gainImplicating perturbationsOsteoblast precursorsPremature suture fusionSequencing analysisMolecular etiologySequence recognitionMissense mutationsMutationsExome sequencingGenetic etiologyOsteoprogenitor cells
2021
Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity
Park J, Daniels J, Wartewig T, Ringbloom KG, Martinez-Escala ME, Choi S, Thomas JJ, Doukas PG, Yang J, Snowden C, Law C, Lee Y, Lee K, Zhang Y, Conran C, Tegtmeyer K, Mo SH, Pease DR, Jothishankar B, Kwok PY, Abdulla FR, Pro B, Louissaint A, Boggon T, Sosman J, Guitart J, Rao D, Ruland J, Choi J. Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity. Blood 2021, 138: 1225-1236. PMID: 34115827, PMCID: PMC8499046, DOI: 10.1182/blood.2020009655.Peer-Reviewed Original ResearchConceptsPutative driver genesDriver genesCutaneous T-cell lymphomaDisease phenotypePutative tumor suppressorT-cell lymphomaMycosis fungoidesDiverse disease phenotypesPutative genetic causesSezary syndromeDNA/RNA sequencingGenomic analysisRNA sequencingMolecular basisTumor suppressorDisease stageStructural variantsGenetic relationshipsTranscriptional signatureGenesDisease heterogeneityFunctional assaysNovel insightsSkin-homing T cellsLeukemic disease
2016
Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin
Elf S, Lin R, Xia S, Pan Y, Shan C, Wu S, Lonial S, Gaddh M, Arellano M, Khoury H, Khuri F, Lee B, Boggon T, Fan J, Chen J. Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin. Oncogene 2016, 36: 254-262. PMID: 27270429, PMCID: PMC5464402, DOI: 10.1038/onc.2016.196.Peer-Reviewed Original ResearchConceptsLeukemia cellsTumor growthAntimalarial drugsNon-immune hemolytic anemiaCombined treatmentHealthy human donorsLeukemia cell viabilityXenograft nude micePrimary leukemia cellsNormal hematopoietic cellsCell viabilityHuman K562 leukemia cellsCancer cell metabolismRed blood cellsCombined therapyHemolytic anemiaAntileukemia treatmentClinical observationsNude miceHuman patientsHuman donorsAnticancer effectsK562 leukemia cellsMinimal toxicityDihydroartemisinin
2015
AIP1 Expression in Tumor Niche Suppresses Tumor Progression and Metastasis
Ji W, Li Y, He Y, Yin M, Zhou HJ, Boggon TJ, Zhang H, Min W. AIP1 Expression in Tumor Niche Suppresses Tumor Progression and Metastasis. Cancer Research 2015, 75: 3492-3504. PMID: 26139244, PMCID: PMC4558200, DOI: 10.1158/0008-5472.can-15-0088.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBreast NeoplasmsCarrier ProteinsCell Line, TumorEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticGuanylate KinasesHumansMelanoma, ExperimentalMiceNeoplasm MetastasisNeovascularization, PathologicProtein Kinase InhibitorsSignal TransductionTumor MicroenvironmentVascular Endothelial Growth Factor Receptor-2ConceptsEpithelial-mesenchymal transitionPremetastatic niche formationTumor growthAugments tumor growthBreast cancer modelSuppresses tumor progressionVascular endothelial cellsNiche formationSystemic administrationCancer modelVEGFR2 kinase inhibitorTumor neovascularizationTumor progressionTumor angiogenesisTumor microenvironmentTumor cellsEndothelial cellsMetastasisKinase inhibitorsTumor nicheVascular ECsSpecific deletionVascular environmentEMT switchAIP1 gene
2001
G-Protein Signaling Through Tubby Proteins
Santagata S, Boggon T, Baird C, Gomez C, Zhao J, Shan W, Myszka D, Shapiro L. G-Protein Signaling Through Tubby Proteins. Science 2001, 292: 2041-2050. PMID: 11375483, DOI: 10.1126/science.1061233.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsCell MembraneCell NucleusCells, CulturedCrystallography, X-RayGene Expression RegulationGTP-Binding Protein alpha Subunits, Gq-G11Heterotrimeric GTP-Binding ProteinsHumansIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsIsoenzymesMembrane LipidsMiceModels, BiologicalMolecular Sequence DataNuclear Localization SignalsObesityPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhospholipase C betaPhosphorylationProtein Structure, TertiaryProteinsReceptor, Serotonin, 5-HT2CReceptors, MuscarinicReceptors, SerotoninRecombinant Fusion ProteinsSignal TransductionTranscription FactorsType C PhospholipasesConceptsTubby-like protein 3G protein signalingTubby proteinTubby domainTranscription regulatorsPlasma membranePhospholipase C-betaReceptor-mediated activationHeterotrimeric GTPSignal transductionGene expressionMolecular mechanismsTubbyC betaCarboxyl terminalCell nucleiMaturity-onset obesityProteinX-ray crystallographyProtein 3SignalingRegulatorMembranePhosphatidylinositolTransduction