About
Titles
Research Scientist
Biography
Dr. Kohei Kume completed his PhD at Iwate University (Morioka, Japan) in 2011 with mentorship from Yasushi Saitoh, PhD. After a postdoctoral training at Iwate Medical University with mentorship from Satoshi S. Nishizuka MD, PhD, he joined Dr. Markus Müschen’s laboratory in 2017 at the Beckman Research Institute of the City of Hope. He is currently a Research Scientist in Dr. Müschen’s laboratory at Yale University, and studies the mechanisms and functional significance of autonomous Ca2+ oscillations in oncogenic signaling of multiple B-cell malignancies.
Appointments
Hematology
Research ScientistPrimary
Other Departments & Organizations
Education & Training
- Associate Research Scientist
- Yale University
- Staff Scientist
- City of Hope
- Associate Instructor
- Iwate Medical University
- Postdoctoral Fellow
- Iwate Medical University School of Medicine
- PhD
- Iwate University, Bioresources Sciences (2011)
Research
Overview
Medical Research Interests
Cell Size; Drug Resistance; Leukemia; Lipid Metabolism; Lymphoma; Oncogenes; Optogenetics; Protein Array Analysis; Proteogenomics
Public Health Interests
Biomarkers; Cancer
ORCID
0000-0003-2856-5970- View Lab Website
Lab Website
Research at a Glance
Yale Co-Authors
Frequent collaborators of Kohei Kume's published research.
Publications Timeline
A big-picture view of Kohei Kume's research output by year.
Research Interests
Research topics Kohei Kume is interested in exploring.
Markus Müschen, MD, PhD
Kadriye Nehir Cosgun, PhD
Jaewoong Lee, PhD
Etienne Leveille, MD
Mark Robinson, PhD
Shalin Kothari, MD
36Publications
495Citations
Protein Array Analysis
Drug Resistance
Publications
2024
Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies
Robinson M, Li Q, Zhang C, Zhan C, Cheng Z, Kume K, Cosgun K, Kothari S, Agadzhanian N, Nakada D, Müschen M. Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies. Blood 2024, 144: 4164-4164. DOI: 10.1182/blood-2024-205729.Peer-Reviewed Original ResearchConceptsB-ALL cell linesB-ALLB cellsCell linesTherapeutic vulnerabilitiesGene dependenciesNAD+ synthesisMature B-cell lymphomasElimination of B cellsTreatment of B-ALLNAD+ salvageChemotherapy-based regimensEffects of NAMPT inhibitionB-cell depletionB-cell lymphomaB-lymphoid malignanciesB-ALL cellsNAMPT inhibitorsInhibition of NAMPTATP-utilizing enzymesNAD+ salvage pathwayDrug repurposing platformNAD biosynthetic pathwayNear-complete ablationDe novo pathwayIdentification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Cheng Z, Oulghazi S, Berning P, Fonseca-Arce D, Kume K, Fontaine J, Chan L, Lee J, Yu F, Qian Z, Song J, Chan W, Chen J, Taketo M, Schjerven H, Müschen M. Identification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies. Blood 2024, 144: 4125-4125. DOI: 10.1182/blood-2024-208125.Peer-Reviewed Original ResearchConceptsProtein degradation pathwaysB-ALL cellsProtein degradationRepression of MYCTranscriptional activity of MYCCell deathAcute cell deathLoss of colony formationChIP-seq analysisActive enhancer marksB-cell malignanciesSuper-enhancer regionsActivation of MYCIkaros transcription factorB-lymphoid cellsCell linesB cell identityDefective protein degradationB-cateninNon-lymphoid cell linesDegradation pathwayMantle cell lymphomaProtein levelsB-ALLChIP-seqPKCδ-Mediated Phosphorylation of CD25 Initiates Feedback Control of Oncogenic Tyrosine Kinases in Acute Lymphoblastic Leukemia
Sun R, Lee J, Artadji D, Robinson M, Kume K, Cheng Z, Cosgun K, Chan L, Leveille E, Ma N, Geng H, Paietta E, Vaidehi N, Müschen M. PKCδ-Mediated Phosphorylation of CD25 Initiates Feedback Control of Oncogenic Tyrosine Kinases in Acute Lymphoblastic Leukemia. Blood 2024, 144: 632-632. DOI: 10.1182/blood-2024-211038.Peer-Reviewed Original ResearchConceptsB-ALL cellsPatient-derived xenograftsPh+ B-ALLPh-like B-ALLAntibody-drug conjugatesB-ALL casesB-ALLCre-mediated deletionOncogenic tyrosine kinasesBCR-ABL1Tyrosine kinase signalingSurface expressionColony formation capacityCD25 mRNACell surface expression of CD25Tyrosine kinaseGenetic deletionSurface expression of CD25Oncogenic tyrosine kinase signalingKinase signalingOncogene BCR-ABL1Transplant recipient miceControl ADCNegative feedback regulationExpression of CD25Mechanism of Negative Feedback Regulation of Oncogenic BCR-Signaling in Mature B-Cell Lymphoma
Sun R, Lee J, Robinson M, Kume K, Zhan C, Cheng Z, Cosgun K, Chan L, Leveille E, Kothari S, Katz S, Ma N, Vykunta V, Shy B, Hodson D, Marson A, Vaidehi N, Müschen M. Mechanism of Negative Feedback Regulation of Oncogenic BCR-Signaling in Mature B-Cell Lymphoma. Blood 2024, 144: 3003-3003. DOI: 10.1182/blood-2024-211693.Peer-Reviewed Original ResearchConceptsB-cell lymphomaGC B cellsB-cell lymphoma cellsB cellsBCR signalingGerminal centersProteolytic cleavageNK cellsLymphoma cellsMantle cell lymphoma xenograftsAggressive B-cell lymphomasMature B-cell lymphomasB-cell lymphoma subtypesGerminal center B cellsSpontaneous germinal centersGlobal phosphoproteomic studiesActivation marker CD69Aggressiveness of diseaseCD25 surface expressionMechanism of negative feedback regulationB cell autoimmunityFollicular dendritic cellsHuman germinal centerCa2+ oscillationsExpressed increased levelsTargeted Dynamic Phospho-Proteogenomic Analysis of Gastric Cancer Cells Suggests Host Immunity Provides Survival Benefit
Kume K, Iida M, Iwaya T, Yashima-Abo A, Koizumi Y, Endo A, Wade K, Hiraki H, Calvert V, Wulfkuhle J, Espina V, Siwak D, Lu Y, Takemoto K, Suzuki Y, Sasaki Y, Tokino T, Petricoin E, Liotta L, Mills G, Nishizuka S. Targeted Dynamic Phospho-Proteogenomic Analysis of Gastric Cancer Cells Suggests Host Immunity Provides Survival Benefit. Molecular & Cellular Proteomics 2024, 23: 100870. PMID: 39461475, PMCID: PMC11621936, DOI: 10.1016/j.mcpro.2024.100870.Peer-Reviewed Original ResearchAltmetricConceptsDNA-damaging drugsTotal lymphocyte countCell linesResistance to DNA damaging drugsPD-L1Adjuvant chemotherapyProtein dynamicsProtein-level regulationSurvival benefitCopy number lossExpression time courseGastric cancerRelapse-free survival rateGastric cancer cellsHost immunityAssociated with prolonged survivalIncreased STAT1 phosphorylationResistance to other drugsGlobal protein dynamicsImmune checkpoint blockadePD-L1 positivityPD-L1 expressionAdvanced gastric cancerExpression of STAT1Molecular targeted drugs
2023
Immunoglobulin Light Chains Control Permissiveness to Malignant B-Cell Transformation By RAS-Pathway Lesions
Chan L, Kume K, Hurtz C, Robinson M, Cosgun K, Müschen M. Immunoglobulin Light Chains Control Permissiveness to Malignant B-Cell Transformation By RAS-Pathway Lesions. Blood 2023, 142: 2974. DOI: 10.1182/blood-2023-190163.Peer-Reviewed Original ResearchConceptsJeKo-1 cellsB cell precursorsMature B cellsB cellsMantle cell lymphoma cellsCell lymphoma cellsGenetic ablationImmunoglobulin light chainsRAS activationOncogenic RASMalignant transformationB-cell acute lymphoblastic leukemiaConventional light chainsRAS pathwayLymphoma cellsCell deathOncogenic RAS activationLight chainAcute lymphoblastic leukemiaMature B-cell lymphomasTransgenic mouse modelB-cell lymphomaB-cell malignanciesMalignant B-cell transformationKappa-LCMYC to BCL6 State-Transitions Determine Cell Size and Metabolic Fluctuations and Define a Novel Biorhythm in B-Cell Malignancies
Cheng Z, Kume K, Müschen M. MYC to BCL6 State-Transitions Determine Cell Size and Metabolic Fluctuations and Define a Novel Biorhythm in B-Cell Malignancies. Blood 2023, 142: 2769. DOI: 10.1182/blood-2023-190972.Peer-Reviewed Original ResearchConceptsGerminal center-derived B-cell lymphomaB cell developmentCell size fluctuationsCell cycleImmunoglobulin light chain gene recombinationDNA damage-induced apoptosisDistinct cellular statesNormal B cell developmentDamage-induced apoptosisExit cell cycleCell sizeB cell transitionGene expression profilesQuiescent phenotypeOncogenic tyrosine kinasesCell cycle arrestActivation of autophagySingle-cell sortingCellular statesCell divisionHigher glycolysis activityMYC transcriptionB cell cycleSuppression of glycolysisExpression profilesOptogenetic 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 ResearchConceptsB-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 ResearchConceptsB-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 ResearchConceptsFavorable 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 pathway
Academic Achievements & Community Involvement
honor ASH Abstract Achievement Award
National AwardDetails11/12/2021, 11/29/2019, 10/29/2018, 10/31/2017United Stateshonor Research Grant from The Japan Prize Foundation
International AwardDetails04/01/2012Japan
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Mailing Address
Müschen Lab
300 George Street
New Haven, CT 06511
United States