Featured Publications
Comparative Molecular Life History of Spontaneous Canine and Human Gliomas
Amin S, Anderson K, Boudreau C, Martinez-Ledesma E, Kocakavuk E, Johnson K, Barthel F, Varn F, Kassab C, Ling X, Kim H, Barter M, Lau C, Ngan C, Chapman M, Koehler J, Long J, Miller A, Miller C, Porter B, Rissi D, Mazcko C, LeBlanc A, Dickinson P, Packer R, Taylor A, Rossmeisl J, Woolard K, Heimberger A, Levine J, Verhaak R. Comparative Molecular Life History of Spontaneous Canine and Human Gliomas. Cancer Cell 2020, 37: 243-257.e7. PMID: 32049048, PMCID: PMC7132629, DOI: 10.1016/j.ccell.2020.01.004.Peer-Reviewed Original ResearchConceptsComparative genomic analysisDNA methylation patternsReceptor tyrosine kinasesCell cycle pathwayGenomic analysisMethylation sequencingLife historyMutational processesTyrosine kinaseHigh similarityHuman gliomasTumorigenic mechanismsHost environmentMutational rateSomatic alterationsSporadic gliomasIDH1 R132Canine gliomasMolecular profileGlioma etiologyHuman pediatricPediatric gliomasTranscriptomeKinaseUnique insightsTruncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma
Lissanu Deribe Y, Shi Y, Rai K, Nezi L, Amin S, Wu C, Akdemir K, Mahdavi M, Peng Q, Chang Q, Hornigold K, Arold S, Welch H, Garraway L, Chin L. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e1296-e1305. PMID: 26884185, PMCID: PMC4780599, DOI: 10.1073/pnas.1513801113.Peer-Reviewed Original ResearchConceptsPREX2 mutationsCross-species gene expression analysisGuanine nucleotide exchange factor activityNucleotide exchange factor activityGene expression regulationPI3K/PTEN/Akt pathwayExchange factor activityMelanoma developmentPTEN/AKT pathwayCell cycle regulatorsGene expression analysisExpression regulationGEF activityCytoskeleton organizationCDKN1C geneRegulatory regionsExpression analysisGene expressionCycle regulatorsDNA hypomethylationCell cycleChromosome 11Tumor suppressorBiological pathwaysMechanistic basis
2021
Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy
Terranova C, Tang M, Maitituoheti M, Raman A, Ghosh A, Schulz J, Amin S, Orouji E, Tomczak K, Sarkar S, Oba J, Creasy C, Wu C, Khan S, Lazcano R, Wani K, Singh A, Barrodia P, Zhao D, Chen K, Haydu L, Wang W, Lazar A, Woodman S, Bernatchez C, Rai K. Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy. Cell Reports 2021, 36: 109410. PMID: 34289358, PMCID: PMC8369408, DOI: 10.1016/j.celrep.2021.109410.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationChromatinEnhancer of Zeste Homolog 2 ProteinFemaleGTP PhosphohydrolasesHistonesHumansMelanocytesMelanomaMembrane ProteinsMesodermMice, NudeMitogen-Activated Protein Kinase KinasesMutationNeoplasm MetastasisPolycomb Repressive Complex 2Transcription, GeneticTumor BurdenConceptsHistone H3 lysine 27 trimethylationH3 lysine 27 trimethylationBivalent chromatin stateCell identity genesLysine 27 trimethylationKey epigenetic alterationsNRAS mutantsMaster transcription factorBivalent domainsChromatin statePRC2 inhibitionEpigenetic elementsTranscription factorsEpigenetic alterationsGenetic driversMesenchymal phenotypeNRAS-mutant melanomaState profilingTherapeutic vulnerabilitiesInvasive capacityPharmacological inhibitionMutantsTherapeutic strategiesMelanoma samplesMutant melanoma patients
2020
Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma
Maitituoheti M, Keung E, Tang M, Yan L, Alam H, Han G, Singh A, Raman A, Terranova C, Sarkar S, Orouji E, Amin S, Sharma S, Williams M, Samant N, Dhamdhere M, Zheng N, Shah T, Shah A, Axelrad J, Anvar N, Lin Y, Jiang S, Chang E, Ingram D, Wang W, Lazar A, Lee M, Muller F, Wang L, Ying H, Rai K. Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma. Cell Reports 2020, 33: 108293. PMID: 33086062, PMCID: PMC7649750, DOI: 10.1016/j.celrep.2020.108293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell Line, TumorDNA-Binding ProteinsFemaleGenes, Tumor SuppressorGlucoseGlycolysisHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHumansInsulinIntercellular Signaling Peptides and ProteinsMaleMelanomaMiceMice, Inbred C57BLMice, NudeMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsReceptor, IGF Type 1Regulatory Sequences, Nucleic AcidSignal TransductionXenograft Model Antitumor AssaysConceptsKMT2D-deficient cellsInsulin growth factorEnhancer reprogrammingIGF1R-AktMelanocyte-specific deletionMutant melanomaMouse modelTumor typesTherapeutic interventionsPharmacological inhibitionPathway inhibitorPotent tumor suppressorIGF signalingGrowth factorMelanomaPooled RNAi screensSomatic point mutationsTumor suppressorKey metabolic pathwaysFrequent lossGlycolysisGlycolysis enzymesTumorigenesisGlycolysis pathwayMetabolic pathwaysKMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer
Alam H, Tang M, Maitituoheti M, Dhar S, Kumar M, Han C, Ambati C, Amin S, Gu B, Chen T, Lin Y, Chen J, Muller F, Putluri N, Flores E, DeMayo F, Baseler L, Rai K, Lee M. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell 2020, 37: 599-617.e7. PMID: 32243837, PMCID: PMC7178078, DOI: 10.1016/j.ccell.2020.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntimetabolitesApoptosisBiomarkers, TumorCell ProliferationDeoxyglucoseDNA-Binding ProteinsEnhancer Elements, GeneticGene Expression Regulation, NeoplasticGlycolysisHistone-Lysine N-MethyltransferaseHistonesHumansLung NeoplasmsMiceMice, KnockoutMice, NudeMutationMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsPeriod Circadian ProteinsPrognosisTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLung cancerLung-specific lossHuman lung cancer cellsExpression of Per2Lung cancer cellsHistone methyltransferase KMT2DLung tumor suppressorTumor suppressive roleMultiple glycolytic genesLung tumorigenesisEpigenetic modifiersPharmacological inhibitionTherapeutic vulnerabilitiesGlycolytic inhibitorCancerCancer cellsKMT2DFunction mutationsTumor suppressorPer2GlycolysisGlycolytic genesMutationsMice
2019
p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors
Carugo A, Minelli R, Sapio L, Soeung M, Carbone F, Robinson F, Tepper J, Chen Z, Lovisa S, Svelto M, Amin S, Srinivasan S, Del Poggetto E, Loponte S, Puca F, Dey P, Malouf G, Su X, Li L, Lopez-Terrada D, Rakheja D, Lazar A, Netto G, Rao P, Sgambato A, Maitra A, Tripathi D, Walker C, Karam J, Heffernan T, Viale A, Roberts C, Msaouel P, Tannir N, Draetta G, Genovese G. p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors. Cancer Cell 2019, 35: 204-220.e9. PMID: 30753823, PMCID: PMC7876656, DOI: 10.1016/j.ccell.2019.01.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAutophagyCell Line, TumorCyclin-Dependent Kinase Inhibitor p16Endoplasmic Reticulum StressFemaleGene Expression Regulation, NeoplasticHumansMaleMice, 129 StrainMice, Inbred C57BLMice, KnockoutProteasome InhibitorsProteostasisProto-Oncogene Proteins c-mycRhabdoid TumorSignal TransductionSMARCB1 ProteinTumor Cells, CulturedTumor Suppressor Protein p53Unfolded Protein ResponseConceptsMalignant rhabdoid tumorRhabdoid tumorUnfolded protein responseClinical pathological featuresAggressive pediatric malignancyCombination of agentsPediatric malignanciesMouse modelP53 axisMosaic mouse modelChromatin remodeling genesER stress responseTumorsHuman oncogenesisBiallelic inactivationMalignancyProtein responseDramatic activationHuman diseasesMaster regulatorExquisite sensitivityAutophagic machineryAgentsDiseaseStress response
2018
An in vivo screen identifies PYGO2 as a driver for metastatic prostate cancer
Lu X, Pan X, Wu C, Zhao D, Feng S, Zang Y, Lee R, Khadka S, Amin S, Jin E, Shang X, Deng P, Luo Y, Morgenlander W, Weinrich J, Lu X, Jiang S, Chang Q, Navone N, Troncoso P, DePinho R, Wang Y. An in vivo screen identifies PYGO2 as a driver for metastatic prostate cancer. Cancer Research 2018, 78: canres.3564.2017. PMID: 29769196, PMCID: PMC6381393, DOI: 10.1158/0008-5472.can-17-3564.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCarcinogenesisCell Line, TumorDisease ProgressionGene Expression Regulation, NeoplasticHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsLymph NodesMaleMiceMice, NudeNeoplasm GradingOncogenesPC-3 CellsProstatic NeoplasmsTranscriptional ActivationUp-RegulationWnt Signaling PathwayConceptsProstate cancer progressionDepth functional analysisCancer progressionWnt/β-catenin signalingCancer cell invasionΒ-catenin signalingFunctional genomicsProstate cancerTranscriptional activationCopy number aberrationsTranscriptomic datasetsFinger 2New oncogenePygo2's functionFunctional driversFunctional analysisLymph nodesImpairs tumor progressionChromosomal instabilityPutative oncogeneCell invasionNumber aberrationsPositive hitsAmplification/overexpressionOncogene
2017
Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer
Genovese G, Carugo A, Tepper J, Robinson F, Li L, Svelto M, Nezi L, Corti D, Minelli R, Pettazzoni P, Gutschner T, Wu C, Seth S, Akdemir K, Leo E, Amin S, Molin M, Ying H, Kwong L, Colla S, Takahashi K, Ghosh P, Giuliani V, Muller F, Dey P, Jiang S, Garvey J, Liu C, Zhang J, Heffernan T, Toniatti C, Fleming J, Goggins M, Wood L, Sgambato A, Agaimy A, Maitra A, Roberts C, Wang H, Viale A, DePinho R, Draetta G, Chin L. Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer. Nature 2017, 542: 362-366. PMID: 28178232, PMCID: PMC7609022, DOI: 10.1038/nature21064.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Pancreatic DuctalDeoxycytidineEndoplasmic Reticulum StressFemaleGemcitabineGenes, mycGenes, rasHumansMaleMAP Kinase Kinase 4MAP Kinase Signaling SystemMesodermMiceMosaicismOncogene Protein p55(v-myc)Pancreatic NeoplasmsProteolysisProto-Oncogene Proteins p21(ras)SMARCB1 ProteinTranscriptome
2016
miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis
Xue J, Zhou A, Wu Y, Morris S, Lin K, Amin S, Verhaak R, Fuller G, Xie K, Heimberger A, Huang S. miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis. Cancer Research 2016, 76: 4293-4304. PMID: 27246830, PMCID: PMC5033679, DOI: 10.1158/0008-5472.can-15-3073.Peer-Reviewed Original ResearchConceptsProtocadherin-8Glioma tumorigenesisProtein-coding genesMiRNA gene transcriptionCandidate target genesExpression of STAT3Gene transcriptionBioinformatics analysisTarget genesSTAT3/miRSTAT3 knockdownPCDH8 expressionSTAT3 inhibitorAberrant activationGlioblastoma tissuesSTAT3Expression levelsInvasive capacityTranscriptionTumorigenesisGlioma progressionGenesCritical roleKnockdownP-STAT3
2012
Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells
Tian Z, Zhao J, Tai Y, Amin S, Hu Y, Berger A, Richardson P, Chauhan D, Anderson K. Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells. Blood 2012, 120: 3958-3967. PMID: 22983447, PMCID: PMC3496955, DOI: 10.1182/blood-2012-01-401794.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBoron CompoundsCell DeathCell Line, TumorCell MovementCell SurvivalCluster AnalysisDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, Tumor SuppressorGlycineHumansImidazolesMiceMicroRNAsMultiple MyelomaProto-Oncogene Proteins c-pim-1PyridazinesSignal TransductionXenograft Model Antitumor AssaysConceptsMultiple myelomaMM cellsPim-1Tumor suppressor geneTranscriptional regulationPim-1 overexpressionBiochemical inhibitorsApoptotic signalingRole of miRTumor suppressorMiR33bMM cell viabilityCell deathPatient MM cellsMM xenograft modelNovel therapeutic strategiesLuciferase activityColony formationOverexpressionMiR profilingTumor pathogenesisInvestigational agentsCritical roleRegulationCell viability
2011
Significant Biological Role of Sp1 Transactivation in Multiple Myeloma
Fulciniti M, Amin S, Nanjappa P, Rodig S, Prabhala R, Li C, Minvielle S, Tai Y, Tassone P, Avet-Loiseau H, Hideshima T, Anderson K, Munshi N. Significant Biological Role of Sp1 Transactivation in Multiple Myeloma. Clinical Cancer Research 2011, 17: 6500-6509. PMID: 21856768, PMCID: PMC4318245, DOI: 10.1158/1078-0432.ccr-11-1036.Peer-Reviewed Original ResearchConceptsBone marrow stromal cellsSp1 activitySp1 knockdownTranscription factor specificity protein 1Caspase-9-dependent apoptosisCritical cell cycleSp1 DNA bindingSp1-responsive promotersSpecificity protein 1Cell growthFirefly luciferase reporter geneImportant transcription factorImportant regulatory roleLuciferase reporter geneSignificant biological roleApoptosis-related genesSp1 transactivationShort hairpin RNASp1 DNACellular processesTranscription factorsPromoter elementsMarrow stromal cellsReporter geneMM cells
2010
Elevated IL-17 produced by T h 17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma
Prabhala R, Pelluru D, Fulciniti M, Prabhala H, Nanjappa P, Song W, Pai C, Amin S, Tai Y, Richardson P, Ghobrial I, Treon S, Daley J, Anderson K, Kutok J, Munshi N. Elevated IL-17 produced by T h 17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 2010, 115: 5385-5392. PMID: 20395418, PMCID: PMC2902136, DOI: 10.1182/blood-2009-10-246660.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHealthy donor peripheral blood mononuclear cellsDonor peripheral blood mononuclear cellsIL-17Multiple myelomaBM mononuclear cellsMyeloma cell growthBone marrowBone marrow stromal cellsIL-22Mononuclear cellsHealthy donorsImmune functionT helper 17 (Th17) cellsElevated IL-17Observed immune dysfunctionSerum IL-17IL-23 productionBlood mononuclear cellsAnti-MM activityIL-17 receptorHuman multiple myelomaMurine xenograft modelImportant therapeutic targetMM pathobiology