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 ResearchImpact of COVID-19 pandemic on physician-scientist trainees to faculty one year into the pandemic
Obradovic A, Toubat O, Chen N, Siebert A, Jansen C, Christophers B, Leveille E, Noch E, Kwan J. Impact of COVID-19 pandemic on physician-scientist trainees to faculty one year into the pandemic. BMC Medical Education 2024, 24: 587. PMID: 38807106, PMCID: PMC11134762, DOI: 10.1186/s12909-024-05541-9.Peer-Reviewed Original ResearchConceptsPersonal healthLong-term effects of COVID-19Physician-scientist traineesPhysician-scientistsCross-sectional survey of medical studentsCOVID-19 pandemicSurvey of medical studentsClustering techniqueScientific pursuitsHealth of familiesMultivariate regression analysisEffects of COVID-19ConclusionsThis national surveyLevel of trainingTailored supportPhysician-scientist trainingResearch productivityMental healthFewer physiciansLonger-term impactMedical studentsImpaired productionCOVID-19Long-term effectsReport concerns
2023
CAR T-Related Toxicities Based on Dynamic Proteomic Profiles Identifies Risk Factors for Cytokine Release Syndrome (CRS) and Immune Effector Cell -Associated Neurotoxicity Syndrome (ICANS)
Kewan T, Mirza S, Pine A, Rasheed Y, Hamouche R, Leveille E, Goshua G, Gu S, Liu Y, Vanoudenhove J, Bar N, Neparidze N, Foss F, Gowda L, Isufi I, Halene S, Lee A, Seropian S. CAR T-Related Toxicities Based on Dynamic Proteomic Profiles Identifies Risk Factors for Cytokine Release Syndrome (CRS) and Immune Effector Cell -Associated Neurotoxicity Syndrome (ICANS). Blood 2023, 142: 2132. DOI: 10.1182/blood-2023-187295.Peer-Reviewed Original ResearchCytokine release syndromeDiffuse large B-cell lymphomaCAR T-cell therapyCAR T-cell productsCAR-T productsNon-Hodgkin lymphomaBest cutoff pointMultiple myelomaHigher oddsDay 3Risk factorsTime pointsCutoff pointDay 5Day 0Median absolute lymphocyte countChimeric antigen receptor T cellsRefractory non-Hodgkin lymphomaCAR T-cell infusionAntigen receptor T cellsLarge B-cell lymphomaCAR-T activationFludarabine/cyclophosphamideHigher baseline CRPPossible inflammatory mediatorsOptogenetic Control of Oncogenic Signaling in B-Cell Malignancies
Kume K, Lee J, Cheng Z, Robinson M, Leveille E, Cosgun K, Chan L, Feng Y, Arce D, Khanduja D, Toomre D, Müschen M. Optogenetic Control of Oncogenic Signaling in B-Cell Malignancies. Blood 2023, 142: 4138. DOI: 10.1182/blood-2023-190926.Peer-Reviewed Original ResearchB-cell malignanciesB-cell lymphomaMature B-cell lymphomasB cell deathB cellsB cell developmentGenetic deletionMantle cell lymphomaNF-kB signalingBCR signal inhibitorsB cell precursorsCell of originCell viabilityChronic active BCRB cell survivalB cell receptor signalsHodgkin's diseaseMultiple myelomaNormal B cell developmentPlasma cellsBtk tyrosine kinaseCell lymphomaBurkitt's lymphomaNF-kBSmall molecule inhibitorsSTAT5-Feedback Controls Distinct Metabolic States for Dynamic Transitions between Cellular Activation and Quiescence in Acute Lymphoblastic Leukemia
Kume K, Chen Z, Robinson M, Chan L, Leveille E, Cosgun K, Cheng Z, Arce D, Khanduja D, Graeber T, Müschen M. STAT5-Feedback Controls Distinct Metabolic States for Dynamic Transitions between Cellular Activation and Quiescence in Acute Lymphoblastic Leukemia. Blood 2023, 142: 2977. DOI: 10.1182/blood-2023-191006.Peer-Reviewed Original ResearchB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaLymphoblastic leukemiaPharmacological inhibitionGenetic deletionCellular activationReceptor signalingCell deathBone marrow relapsePoor overall outcomePoor clinical outcomeLeukemia-initiating capacityOncogenic STAT5Mass spectrometry-based metabolomics analysisExpression levelsPhosphorylation of STAT5Flow cytometry analysisMetabolic statePositive MRDRole of mTORMarrow relapseAggressive courseClinical outcomesExcessive protein synthesisMetabolic outcomesRepurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies
Cosgun K, Robinson M, Oulghazi S, Xu L, Xiao G, Chan L, Lee J, Kume K, Leveille E, Arce D, Khanduja D, Feldhahn N, Song J, Chan W, Chen J, Taketo M, Schjerven H, Jellusova J, Kothari S, Davids M, Müschen M. Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies. Blood 2023, 142: 2818. DOI: 10.1182/blood-2023-190522.Peer-Reviewed Original ResearchFavorable safety profileSmall molecule inhibitorsT-lymphoid malignancyΒ-catenin degradationLymphoid malignanciesΒ-cateninInteractome studiesSafety profileClinical trialsMolecule inhibitorsLow nanomolar concentrationsΒ-catenin accumulationSolid tumorsRefractory B-cell malignanciesCell deathPK/PD profilesZinc finger proteinRefractory lymphoid malignanciesChIP-seq analysisPhase 2 trialMYC target genesT-cell lymphomaColony formationRapid nuclear accumulationWnt/β-catenin pathwayDynamic Recruitment of Inhibitory Complexes Controls Oncogenic Signaling in B-Cell Malignancies
Sun R, Lee J, Robinson M, Kume K, Ma N, Cosgun K, Chan L, Antoshkina I, Khanduja D, Leveille E, Katz S, Chen J, Paietta E, Vaidehi N, Müschen M. Dynamic Recruitment of Inhibitory Complexes Controls Oncogenic Signaling in B-Cell Malignancies. Blood 2023, 142: 719. DOI: 10.1182/blood-2023-189742.Peer-Reviewed Original ResearchB-cell malignanciesB-cell lymphomaHigher serum levelsMature B-cell lymphomasSoluble CD25Serum levelsOncogenic signalingMouse modelB cellsAggressive B-cell lymphomasAcceleration of diseaseActivation of inhibitoryPoor clinical outcomeCD25 surface expressionB cell subsetsRole of CD25Patient-derived xenograftsB cell populationsB-cell receptor signalingB-cell leukemiaGenetic mouse modelsKnockin mouse modelCell deathMature B cell populationClinical outcomesComputational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies
Li Q, Robinson M, Leveille E, Zhang C, Sun R, Cheng Z, Kume K, Cosgun K, Kothari S, Khanduja D, Nakada D, Müschen M. Computational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies. Blood 2023, 142: 418. DOI: 10.1182/blood-2023-190269.Peer-Reviewed Original ResearchSmall molecule inhibitorsDrug discovery toolNAMPT inhibitorsCompound screenCell type-specific targetsCell linesMolecule inhibitorsPurine/pyrimidine metabolismTumor cell linesEnergy metabolismSalvage biosynthesis pathwaySolid tumor cell linesB cell developmentCellular energy metabolismB cell signalingAmino acid metabolismCell cycle arrestDiscovery toolDepletion of metabolitesBiosynthesis pathwayCompetitive fitnessRate-limiting enzymeNAMPT deletionConditional mouse modelEnergy stressGenetic Knockin Approaches to Reconstructing DLBCL-Subtypes from Human Germinal Center B-Cells
Khanduja D, Robinson M, Arce D, Klemm L, Leveille E, Kothari S, Caeser R, Hodson D, Müschen M. Genetic Knockin Approaches to Reconstructing DLBCL-Subtypes from Human Germinal Center B-Cells. Blood 2023, 142: 1627. DOI: 10.1182/blood-2023-190634.Peer-Reviewed Original ResearchSecondary lymphoid organsGerminal center B cellsMYD88 L265P mutationLymphoid organsLymph nodesB cellsL265P mutationHuman germinal center B cellsDLBCL subtypesNSG miceTonsillar germinal center B cellsLymphoma developmentPreclinical testingLymphoid tissue inducer cellsTransgenic expressionPoor clinical outcomeWild-type mutationsGenetic mouse modelsExon 5GC B cellsNBSGW miceClinical outcomesLTi cellsLymphoid folliclesInducer cells
2022
Genetic Modeling of B-cell State Transitions for Rational Design of Lymphoma Therapies.
Leveille E, Kothari S, Müschen M. Genetic Modeling of B-cell State Transitions for Rational Design of Lymphoma Therapies. Blood Cancer Discovery 2022, 4: 8-11. PMID: 36534735, PMCID: PMC9816816, DOI: 10.1158/2643-3230.bcd-22-0180.Commentaries, Editorials and LettersProteomic Profiles of Cytokine Release Syndromes Following Lisocabtagene Maraleucel and Idecabtagene Vicleucel
Mirza A, Pine A, Rasheed Y, Hamouche R, Leveille E, Goshua G, Gu S, Liu Y, VanOudenhove J, Bar N, Neparidze N, Foss F, Gowda L, Isufi I, Halene S, Lee A, Seropian S. Proteomic Profiles of Cytokine Release Syndromes Following Lisocabtagene Maraleucel and Idecabtagene Vicleucel. Blood 2022, 140: 10410-10412. DOI: 10.1182/blood-2022-168374.Peer-Reviewed Original ResearchSYK and ZAP70 kinases in autoimmunity and lymphoid malignancies
Leveille E, Chan LN, Mirza AS, Kume K, Müschen M. SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies. Cellular Signalling 2022, 94: 110331. PMID: 35398488, DOI: 10.1016/j.cellsig.2022.110331.Peer-Reviewed Original ResearchConceptsChronic lymphocytic leukemiaB-cell malignanciesT cell receptorB cell receptorB-cell chronic lymphocytic leukemiaPathological B-cellsPoor clinical outcomeAcute lymphoblastic leukemiaExpression of SykT lymphocyte developmentClinical outcomesAggressive diseaseActivation of NFATAutoimmune diseasesLymphoblastic leukemiaT lymphocytesLymphocytic leukemiaCell lymphomaLymphoid malignanciesB cellsPI3K-pathwayOncogenic driversMalignancyNegative selectionPremalignant cells
2021
GCH1 mutations in hereditary spastic paraplegia.
Varghaei P, Yoon G, Estiar MA, Veyron S, Leveille E, Dupré N, Trempe JF, Rouleau GA, Gan-Or Z. GCH1 mutations in hereditary spastic paraplegia. Clinical Genetics 2021, 100: 51-58. PMID: 33713342, DOI: 10.1111/cge.13955.Peer-Reviewed Original ResearchMetabolic determinants of B-cell selection
Chan LN, Aghania E, Leveille E, Müschen M. Metabolic determinants of B-cell selection. Biochemical Society Transactions 2021, 49: 1467-1478. PMID: 34196360, DOI: 10.1042/bst20201316.BooksConceptsB cellsAutoimmune diseasesB cell selectionB cell developmentImmune systemNegative B cell selectionRisk of developmentAutoreactive B cellsB-cell malignanciesAdaptive immune protectionAdaptive immune systemAntibody-producing cellsPremalignant B cellsEarly B cell developmentHarmful autoantibodiesHigh-affinity antibodiesImmune protectionAutoreactive clonesChronic restrictionBone marrowMalignant transformationMetabolic determinantsDiseaseLymphomaLeukemiaGenetic Events Inhibiting Apoptosis in Diffuse Large B Cell Lymphoma.
Leveille E, Johnson NA. Genetic Events Inhibiting Apoptosis in Diffuse Large B Cell Lymphoma. Cancers 2021, 13 PMID: 33946435, PMCID: PMC8125500, DOI: 10.3390/cancers13092167.Peer-Reviewed Original ResearchInvestigating the relationship between the SNCA gene and cognitive abilities in idiopathic Parkinson's disease using machine learning.
Ramezani M, Mouches P, Yoon E, Rajashekar D, Ruskey JA, Leveille E, Martens K, Kibreab M, Hammer T, Kathol I, Maarouf N, Sarna J, Martino D, Pfeffer G, Gan-Or Z, Forkert ND, Monchi O. Investigating the relationship between the SNCA gene and cognitive abilities in idiopathic Parkinson's disease using machine learning. Scientific Reports 2021, 11: 4917. PMID: 33649398, PMCID: PMC7921412, DOI: 10.1038/s41598-021-84316-4.Peer-Reviewed Original ResearchEvidence for Non-Mendelian Inheritance in Spastic Paraplegia 7.
Estiar MA, Yu E, Haj Salem I, Ross JP, Mufti K, Akçimen F, Leveille E, Spiegelman D, Ruskey JA, Asayesh F, Dagher A, Yoon G, Tarnopolsky M, Boycott KM, Dupre N, Dion PA, Suchowersky O, Trempe JF, Rouleau GA, Gan-Or Z. Evidence for Non-Mendelian Inheritance in Spastic Paraplegia 7. Movement Disorders : Official Journal Of The Movement Disorder Society 2021 PMID: 33598982, DOI: 10.1002/mds.28528.Peer-Reviewed Original Research
2020
GBA variants in REM sleep behavior disorder: A multicenter study.
Krohn L, Ruskey JA, Rudakou U, Leveille E, Asayesh F, Hu MTM, Arnulf I, Dauvilliers Y, Högl B, Stefani A, Monaca CC, Abril B, Plazzi G, Antelmi E, Ferini-Strambi L, Heidbreder A, Boeve BF, Espay AJ, De Cock VC, Mollenhauer B, Sixel-Döring F, Trenkwalder C, Sonka K, Kemlink D, Figorilli M, Puligheddu M, Dijkstra F, Viaene M, Oertel W, Toffoli M, Gigli GL, Valente M, Gagnon JF, Desautels A, Montplaisir JY, Postuma RB, Rouleau GA, Gan-Or Z. GBA variants in REM sleep behavior disorder: A multicenter study. Neurology 2020, 95: e1008-e1016. PMID: 32591474, PMCID: PMC7668554, DOI: 10.1212/WNL.0000000000010042.Peer-Reviewed Original ResearchAnalysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson’s disease
Brown EE, Blauwendraat C, Trinh J, Rizig M, Nalls MA, Leveille E, Ruskey JA, Jonvik H, Tan MMX, Bandres-Ciga S, Hassin-Baer S, Brockmann K, Infante J, Tolosa E, Ezquerra M, Romdhan S, Benmahdjoub M, Arezki M, Mhiri C, Hardy J, Singleton AB, Alcalay RN, Gasser T, Grosset DG, Williams NM, Pittman A, Gan-Or Z, Fernandez-Santiago R, Brice A, Lesage S, Farrer M, Wood N, Morris HR, Consortium I. Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson’s disease. Neurobiology Of Aging 2020, 97: 148.e17-148.e24. PMID: 32873436, PMCID: PMC7762821, DOI: 10.1016/j.neurobiolaging.2020.07.002.Peer-Reviewed Original ResearchClinical Characterization of Traumatic Acute Interhemispheric Subdural Hematoma.
Léveillé E, Schur S, AlAzri A, Couturier C, Maleki M, Marcoux J. Clinical Characterization of Traumatic Acute Interhemispheric Subdural Hematoma. The Canadian Journal Of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques 2020, 47: 504-510. PMID: 32122420, DOI: 10.1017/cjn.2020.44.Peer-Reviewed Original Research