2024
Clonal Hematopoiesis Is Associated With Cardiomyopathy During Solid Tumor Therapy
Leveille E, Cheheyeb R, Matute-Martinez C, Chen N, Jayakrishnan R, Christofides A, Lin D, Im Y, Biancon G, VanOudenhove J, Halene S, Kwan J. Clonal Hematopoiesis Is Associated With Cardiomyopathy During Solid Tumor Therapy. JACC CardioOncology 2024, 6: 605-607. PMID: 39239339, PMCID: PMC11372300, DOI: 10.1016/j.jaccao.2024.05.013.Peer-Reviewed Original ResearchEzrin drives adaptation of monocytes to the inflamed lung microenvironment.
Gudneppanavar R, Di Pietro C, Oez H, Zhang P, Huang P, Braga C, Tebaldi T, Biancon G, Kim C, Gonzalez A, Halene S, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. The Journal Of Immunology 2024, 212: 0078_5418-0078_5418. DOI: 10.4049/jimmunol.212.supp.0078.5418.Peer-Reviewed Original ResearchRNA-seqActin-binding protein ezrinF-actin distributionImmune response to bacteriaCystic fibrosisIn vitro functional studiesResponse to bacteriaIncreased expression of pro-inflammatory markersCytoskeleton rearrangementF-actinResponse to lung infectionExpressed genesProtein ezrinTranscriptional profilesExpression of pro-inflammatory markersPlasma membranePro-inflammatory markersFunctional studiesEzrinLung extracellular matrixCF miceExtracellular matrixWT micePI3K/Akt signalingLung infection
2023
Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023)
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023). Small Methods 2023, 7 DOI: 10.1002/smtd.202370057.Peer-Reviewed Original ResearchALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control
Gao Y, Zimmer J, Vasic R, Liu C, Gbyli R, Zheng S, Patel A, Liu W, Qi Z, Li Y, Nelakanti R, Song Y, Biancon G, Xiao A, Slavoff S, Kibbey R, Flavell R, Simon M, Tebaldi T, Li H, Halene S. ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control. Cell Reports 2023, 42: 113163. PMID: 37742191, PMCID: PMC10636609, DOI: 10.1016/j.celrep.2023.113163.Peer-Reviewed Original ResearchConceptsAlkB homolog 5Post-transcriptional regulatory mechanismsHematopoietic stemNumerous cellular processesProgenitor cell fitnessEnergy metabolismMitochondrial ATP productionMethyladenosine (m<sup>6</sup>A) RNA modificationTricarboxylic acid cycleCell energy metabolismHuman hematopoietic cellsMitochondrial energy productionCell fitnessCellular processesRNA modificationsRNA methylationRegulatory mechanismsEnzyme transcriptsATP productionHomolog 5Acid cycleΑ-ketoglutarateHematopoietic cellsMessenger RNAΑ-KGMicrofluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection. Small Methods 2023, 7: e2300594. PMID: 37312418, PMCID: PMC10592458, DOI: 10.1002/smtd.202300594.Peer-Reviewed Original ResearchConceptsB cell depletion therapyAcute COVID infectionAnti-spike IgGHigh-risk patientsCoronavirus disease-19COVID-19 pathologyDepletion therapyVaccine protectionAntibody responseCOVID infectionHematologic malignanciesImmune protectionDisease-19Healthy donorsMultiple time pointsSerology assaysBlood samplesSoluble markersB cellsImmunization strategiesPatientsFunctional deficiencySerological analysisTime pointsClonotype diversity
2022
Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis
Öz H, Cheng E, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang P, Huang P, Esquibies S, Britto C, Schupp J, Murray T, Halene S, Krause D, Egan M, Bruscia E. Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis. Cell Reports 2022, 41: 111797. PMID: 36516754, PMCID: PMC9833830, DOI: 10.1016/j.celrep.2022.111797.Peer-Reviewed Original ResearchConceptsC motif chemokine receptor 2Monocytes/macrophagesLung tissue damageCystic fibrosisTissue damageCF lungPulmonary neutrophilic inflammationPro-inflammatory environmentChemokine receptor 2CF lung diseaseNumber of monocytesSpecific therapeutic agentsGrowth factor βCF transmembrane conductance regulatorLung hyperinflammationLung neutrophiliaNeutrophilic inflammationNeutrophil inflammationInflammation contributesLung damageNeutrophil recruitmentLung diseaseLung tissueReceptor 2Therapeutic targetDeconvolution of in vivo protein-RNA contacts using fractionated eCLIP-seq
Biancon G, Busarello E, Joshi P, Lesch B, Halene S, Tebaldi T. Deconvolution of in vivo protein-RNA contacts using fractionated eCLIP-seq. STAR Protocols 2022, 3: 101823. PMID: 36595959, PMCID: PMC9676202, DOI: 10.1016/j.xpro.2022.101823.Peer-Reviewed Original ResearchConceptsProtein-RNA interactionsIndividual RNA-binding proteinsTranscriptome-wide analysisThousands of RNAsProtein-RNA contactsRNA-binding proteinSingle nucleotide levelComputational analysis pipelineRNA processingMulticomponent complexesRNA immunoprecipitationRead countsComplete detailsAnalysis pipelineAdditional levelProteinImmunoprecipitationRNAInteractionComplexesWidespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction
Griffin KN, Walters BW, Li H, Wang H, Biancon G, Tebaldi T, Kaya CB, Kanyo J, Lam TT, Cox AL, Halene S, Chung JJ, Lesch BJ. Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction. Genome Research 2022, 32: 1655-1668. PMID: 36109149, PMCID: PMC9528986, DOI: 10.1101/gr.276578.122.Peer-Reviewed Original ResearchMammalian male reproductionArgonaute 2Distinct nuclear functionsConditional knockoutMale reproductionProtein Argonaute 2Abnormal sperm head morphologyMeiotic chromatinAnimal developmentCytoplasmic roleNuclear functionsMale meiosisNuclear roleMRNA translationAgo2 proteinImportant genesNuclear compartmentMRNA transcriptsBiological relevanceSperm head morphologyHead morphologySpermatogenic cellsWidespread associationChromatinProteinPre-mRNA splicing factor U2AF2 recognizes distinct conformations of nucleotide variants at the center of the pre-mRNA splice site signal
Glasser E, Maji D, Biancon G, Puthenpeedikakkal AMK, Cavender CE, Tebaldi T, Jenkins JL, Mathews DH, Halene S, Kielkopf CL. Pre-mRNA splicing factor U2AF2 recognizes distinct conformations of nucleotide variants at the center of the pre-mRNA splice site signal. Nucleic Acids Research 2022, 50: 5299-5312. PMID: 35524551, PMCID: PMC9128377, DOI: 10.1093/nar/gkac287.Peer-Reviewed Original ResearchMission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies
Figueiredo JC, Hirsch FR, Kushi LH, Nembhard WN, Crawford JM, Mantis N, Finster L, Merin NM, Merchant A, Reckamp KL, Melmed GY, Braun J, McGovern D, Parekh S, Corley DA, Zohoori N, Amick BC, Du R, Gregersen PK, Diamond B, Taioli E, Sariol C, Espino A, Weiskopf D, Gifoni A, Brien J, Hanege W, Lipsitch M, Zidar DA, McAlearney A, Wajnberg A, LaBaer J, Lewis E, Binder RA, Moormann AM, Forconi C, Forrester S, Batista J, Schieffelin J, Kim D, Biancon G, VanOudenhove J, Halene S, Fan R, Barouch DH, Alter G, Pinninti S, Boppana SB, Pati SK, Latting M, Karaba AH, Roback J, Sekaly R, Neish A, Brincks AM, Granger DA, Karger AB, Thyagarajan B, Thomas SN, Klein SL, Cox AL, Lucas T, Furr-Holden D, Key K, Jones N, Wrammerr J, Suthar M, Wong S, Bowman NM, Simon V, Richardson LD, McBride R, Krammer F, Rana M, Kennedy J, Boehme K, Forrest C, Granger SW, Heaney CD, Lapinski M, Wallet S, Baric RS, Schifanella L, Lopez M, Fernández S, Kenah E, Panchal AR, Britt WJ, Sanz I, Dhodapkar M, Ahmed R, Bartelt LA, Markmann AJ, Lin JT, Hagan RS, Wolfgang MC, Skarbinski J. Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies. Open Forum Infectious Diseases 2022, 9: ofac171. PMID: 35765315, PMCID: PMC9129196, DOI: 10.1093/ofid/ofac171.Peer-Reviewed Original ResearchCoronavirus disease 2019Disease 2019Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Healthy pregnant womenInflammatory bowel diseaseLong-term sequelaeHuman immunodeficiency virusSyndrome coronavirus 2Epidemiologic cohort studiesNational Cancer InstituteTransplant recipientsCohort studyBowel diseaseClinical outcomesImmunodeficiency virusPregnant womenAutoimmune diseasesCoronavirus 2Risk factorsCardiovascular diseaseTreatment strategiesImmune responseCancer InstituteIn vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Leukemia 2022, 36: 1313-1323. PMID: 35273342, PMCID: PMC9103411, DOI: 10.1038/s41375-022-01536-x.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeMDS/acute myeloid leukemiaRefractory acute myeloid leukemiaPARP inhibitionVivo anti-tumor effectsAlternate therapeutic optionsSubset of AMLAnti-tumor effectsPre-clinical studiesRibose polymerase inhibitorsSerial transplantation assaysHomologous recombination defectsTherapeutic optionsTreatment optionsOverall engraftmentHigh relapseIDH inhibitionMyeloid leukemiaIsocitrate dehydrogenase 1Small molecule inhibitorsCell frequencyXeno-graftsIDH1/2 mutationsMalignant transformationPrecision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies
Biancon G, Joshi P, Zimmer JT, Hunck T, Gao Y, Lessard MD, Courchaine E, Barentine AES, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon MD, Neugebauer KM, Tebaldi T, Halene S. Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies. Molecular Cell 2022, 82: 1107-1122.e7. PMID: 35303483, PMCID: PMC8988922, DOI: 10.1016/j.molcel.2022.02.025.Peer-Reviewed Original Research
2021
Comprehensive Clinicopathologic and Molecular Analysis of Mast Cell Leukemia With Associated Hematologic Neoplasm: A Report and In-Depth Study of 5 Cases
Li P, Biancon G, Patel T, Pan Z, Kothari S, Halene S, Prebet T, Xu ML. Comprehensive Clinicopathologic and Molecular Analysis of Mast Cell Leukemia With Associated Hematologic Neoplasm: A Report and In-Depth Study of 5 Cases. Frontiers In Oncology 2021, 11: 730503. PMID: 34589432, PMCID: PMC8474637, DOI: 10.3389/fonc.2021.730503.Peer-Reviewed Original ResearchMast cell leukemiaAssociated hematologic neoplasmCell leukemiaHematologic neoplasmsAcute myeloid leukemiaPaucity of casesWhole-exome sequencingAdditional patientsCase seriesAggressive entityRare tumorMyeloid leukemiaAvailable tumorsComprehensive clinicopathologicLeukemiaPatientsNeoplasmsTumorsMolecular analysisClinicopathologicSequencing resultsCasesCombined liver–cytokine humanization comes to the rescue of circulating human red blood cells
Song Y, Shan L, Gbyli R, Liu W, Strowig T, Patel A, Fu X, Wang X, Xu ML, Gao Y, Qin A, Bruscia EM, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Eynon E, Gonzalez DG, Chen J, Krause DS, Alderman J, Halene S, Flavell RA. Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells. Science 2021, 371: 1019-1025. PMID: 33674488, PMCID: PMC8292008, DOI: 10.1126/science.abe2485.Peer-Reviewed Original ResearchConceptsRed blood cellsBlood cellsHuman sickle cell diseaseSickle cell diseaseImmunodeficient murine modelKupffer cell densityBone marrow failureMISTRG miceIntrasplenic injectionSCD pathologyCell diseaseMurine modelComplement C3RBC survivalVivo modelHuman cytokinesPreclinical testingHematopoietic stem cellsHuman red blood cellsMarrow failureFumarylacetoacetate hydrolase geneHuman erythropoiesisHuman liverHuman hepatocytesMice
2020
m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development
Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development. Immunity 2020, 52: 1007-1021.e8. PMID: 32497523, PMCID: PMC7408742, DOI: 10.1016/j.immuni.2020.05.003.Peer-Reviewed Original ResearchConceptsDouble-stranded RNADeleterious innate immune responseMammalian hematopoietic developmentEndogenous double-stranded RNAHematopoietic developmentInnate immune responseAbundant RNA modificationMurine fetal liverPattern recognition receptor pathwaysImmune responseProtein codingDsRNA formationRNA modificationsWriter METTL3Hematopoietic defectsPerinatal lethalityNative stateConditional deletionAberrant innate immune responsesLoss of METTL3Hematopoietic failureReceptor pathwayAberrant immune responsePrevents formationFetal liverIntegrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma
Ziccheddu B, Biancon G, Bagnoli F, De Philippis C, Maura F, Rustad EH, Dugo M, Devecchi A, De Cecco L, Sensi M, Terragna C, Martello M, Bagratuni T, Kastritis E, Dimopoulos MA, Cavo M, Carniti C, Montefusco V, Corradini P, Bolli N. Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma. Blood Advances 2020, 4: 830-844. PMID: 32126144, PMCID: PMC7065476, DOI: 10.1182/bloodadvances.2019000779.Peer-Reviewed Original ResearchConceptsChemotherapy resistanceMultiple myelomaProteasome inhibitorsDouble-refractory multiple myelomaHigh-risk featuresBulk tumor populationOverexpression of MCL1Whole-exome sequencingRefractory patientsImmunomodulatory agentsDisease progressionSame patientNovel treatmentsPatientsKaryotypic eventsEvolution of subclonesMyeloma cellsDrug resistanceMyelomaNovel targetIMiDsTumor populationGene mutationsNext-generation sequencingTP53 pathway
2019
The Genomic and Transcriptomic Landscape of Double-Refractory Multiple Myeloma
Ziccheddu B, Biancon G, De Philippis C, Bagnoli F, Maura F, Dugo M, Devecchi A, De Cecco L, Sensi M, Terragna C, Martello M, Bagratuni T, Kastritis E, Dimopoulos M, Cavo M, Carniti C, Montefusco V, Corradini P, Bolli N. The Genomic and Transcriptomic Landscape of Double-Refractory Multiple Myeloma. Blood 2019, 134: 3056. DOI: 10.1182/blood-2019-122197.Peer-Reviewed Original ResearchMultiple myelomaSpeakers bureauProteasome inhibitorsTP53 mutationsAdvisory CommitteeHigh-dose melphalanMedian overall survivalHigh-risk featuresRefractory multiple myelomaTime of transplantHigh-risk lesionsLine of treatmentNext-generation sequencingBulk tumor populationWhole-exome sequencingInfluence of treatmentMCL1 upregulationOverall survivalRefractory casesComplete responseDisease courseMM patientsPrognostic valueImmunomodulatory agentsPathogenetic roleAnalysis of the genomic and transcriptomic landscape of chemoresistant multiple myeloma
Ziccheddu B, Biancon G, Dugo M, Devecchi A, De Philippis C, Bagnoli F, Maura F, De Cecco L, Gimondi S, Vendramin A, Terragna C, Martello M, Bagratuni T, Kastritis E, Dimopoulos M, Cavo M, Sensi M, Carniti C, Montefusco V, Corradini P, Bolli N. Analysis of the genomic and transcriptomic landscape of chemoresistant multiple myeloma. Clinical Lymphoma Myeloma & Leukemia 2019, 19: e58-e59. DOI: 10.1016/j.clml.2019.09.091.Peer-Reviewed Original ResearchTyrosine kinase inhibition to improve anthracycline-based chemotherapy efficacy in T-cell lymphoma
Magni M, Biancon G, Rizzitano S, Cavanè A, Paolizzi C, Dugo M, Corradini P, Carniti C. Tyrosine kinase inhibition to improve anthracycline-based chemotherapy efficacy in T-cell lymphoma. British Journal Of Cancer 2019, 121: 567-577. PMID: 31474759, PMCID: PMC6889385, DOI: 10.1038/s41416-019-0557-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCell CycleCell SurvivalCyclophosphamideDasatinibDoxorubicinDrug Administration ScheduleDrug SynergismEtoposideGene ExpressionGene Expression ProfilingHumansJurkat CellsLymphoma, T-CellMice, Inbred NODMice, SCIDPrednisoneProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-fynReceptors, Antigen, T-CellRhoA GTP-Binding ProteinTreatment OutcomeUp-RegulationVincristineConceptsT-cell lymphomaPeripheral T-cell lymphomaDrug combinationsTyrosine kinase inhibitor dasatinibVivo xenograft mouse modelMalignant T-cell linesXenograft mouse modelTyrosine kinase inhibitionTumor growth inhibitionKinase inhibitor dasatinibT cell receptorT cell linesT-cell receptor pathwayCell cycle distributionWestern blot analysisChemotherapy efficacyPreclinical modelsConclusionsOur dataMouse modelVivo effectsXenograft modelClinical testingTreatment resultsInhibitor dasatinibLymphomaFrom clonal hematopoiesis to myeloid leukemia and what happens in between: Will improved understanding lead to new therapeutic and preventive opportunities?
Bewersdorf JP, Ardasheva A, Podoltsev NA, Singh A, Biancon G, Halene S, Zeidan AM. From clonal hematopoiesis to myeloid leukemia and what happens in between: Will improved understanding lead to new therapeutic and preventive opportunities? Blood Reviews 2019, 37: 100587. PMID: 31400824, DOI: 10.1016/j.blre.2019.100587.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyeloid neoplasmsClonal hematopoiesisTherapy-related myeloid neoplasmsAnnual progression rateHealthy elderly individualsGenetic testing resultsCardiovascular mortalityHematologic disordersMyeloid leukemiaClinical significanceProgression ratePremalignant stateElderly individualsDiagnostic criteriaPreventive opportunitiesSolid tumorsClinical settingNatural historyFurther studiesPatientsSomatic mutationsRiskHematopoiesisCurrent understandingICUs