2021
Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer
Mirzapoiazova T, Xiao G, Mambetsariev B, Nasser MW, Miaou E, Singhal SS, Srivastava S, Mambetsariev I, Nelson MS, Nam A, Behal A, Arvanitis LD, Atri P, Muschen M, Tissot FLH, Miser J, Kovach JS, Sattler M, Batra SK, Kulkarni P, Salgia R. Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer. Molecular Cancer Therapeutics 2021, 20: 1820-1835. PMID: 34253596, PMCID: PMC8722383, DOI: 10.1158/1535-7163.mct-21-0013.Peer-Reviewed Original ResearchConceptsProtein phosphatase 2APhosphatase 2ASerine/threonine phosphataseDNA damage responseRegulation of apoptosisSmall molecule inhibitorsGlycolytic ATP productionThreonine phosphataseTwo-dimensional cultureLB100ATP productionMolecule inhibitorsPP2AThree-dimensional spheroid modelEndothelial cell monolayersGlucose uptakeCell viabilitySCLC cellsTherapeutic targetApoptosisCell monolayersMass spectrometrySpheroid modelTumor spheroidsCellsPON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis
Pan L, Hong C, Chan LN, Xiao G, Malvi P, Robinson ME, Geng H, Reddy ST, Lee J, Khairnar V, Cosgun KN, Xu L, Kume K, Sadras T, Wang S, Wajapeyee N, Müschen M. PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2016553118. PMID: 33531346, PMCID: PMC7896313, DOI: 10.1073/pnas.2016553118.Peer-Reviewed Original ResearchConceptsTransplant recipient miceDNA double-strand breaksNormal B cell developmentDouble-strand breaksB cell developmentGenetic deletionB cellsLymphoid transcription factorsGlucose transporter GLUT1Gatekeeper functionGlucose uptakeRecipient miceTranscription factorsSomatic recombinationSynthetic lethalityB-cell acute lymphoblastic leukemiaCell developmentMetabolic gatekeeperRefractory B-ALLDeficient murineCell acute lymphoblastic leukemiaPoor clinical outcomeCell typesAcute lymphoblastic leukemiaGlucose transport
2019
Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation
Müschen M. Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation. Nature Reviews Immunology 2019, 19: 337-348. PMID: 30890785, DOI: 10.1038/s41577-019-0154-3.Peer-Reviewed Original ResearchConceptsB cell receptorAutoreactive B cell receptorsLineage-determining transcription factorsMetabolic gatekeeperMitochondrial ATP productionB-cell transformationTranscription factorsEnergy stressPhosphate pathway activityATP productionCell transformationSmall cytoplasmic volumeCell deathPathway activityB cellsEnergy metabolismCell proliferationCytoplasmic volumeCell receptorGlucose uptakeOncogeneB cell proliferationCellsMetabolic demandsAdditional glucose
2016
Transcriptional Control of Glucose and Energy Supply Prevents Oncogenic Signaling and B Cell Transformation
Chan L, Chen Z, Xiao G, Lee J, Geng H, Christian H, Cazzaniga V, Cazzaniga G, Dickins R, Müschen M. Transcriptional Control of Glucose and Energy Supply Prevents Oncogenic Signaling and B Cell Transformation. Blood 2016, 128: 437. DOI: 10.1182/blood.v128.22.437.437.Peer-Reviewed Original ResearchB-cell transcription factorsTranscription factorsCellular ATP levelsPositive regulatorOncogenic signalingNegative regulatorSurvival fitnessCRISPR/Cas9-mediated deletionWild-type PAX5Glucose uptakeQuantitative chromatin immunoprecipitationEffect of PAX5Regions of genesB cell identityProtein levelsCompetitive growth assaysATP levelsTumor suppressive functionSecondary genetic lesionsB-lineageChIPseq dataTranscriptional controlChromatin immunoprecipitationB-cell transformationPatient-derived pre
2015
B-Lymphoid Transcription Factors Restrict Glycolytic Energy Supply for Oncogenic Signaling
Chan L, Chen Z, Braas D, Geng H, Hurtz C, Shojaee S, Cazzaniga V, Ng C, Ernst T, Hochhaus A, Kornblau S, Cazzaniga G, Liu G, Milne T, Koeffler H, Armstrong S, Dickins R, Yamamoto K, Graeber T, Muschen M. B-Lymphoid Transcription Factors Restrict Glycolytic Energy Supply for Oncogenic Signaling. Blood 2015, 126: 1255. DOI: 10.1182/blood.v126.23.1255.1255.Peer-Reviewed Original ResearchGlycolytic energy supplyLKB1-AMPKB cellsTranscription factorsGlucose uptakeMyeloid leukemiaMyeloid malignanciesDeletion of Lkb1Unknown functional significanceB-lineage leukemiasTranscriptional repressionTranscriptional programsMyeloid leukemia cellsLineage conversionHematopoietic progenitor cellsOncogenic signalingClinical characteristicsLineage shiftGenetic lesionsCell deathGlycolytic reserveOncogenic lesionsLeukemia casesInsulin receptorGlucocorticoid receptor