Lars Klemm
Research AssociateCards
About
Research
Publications
2021
Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer
Sadras T, Martin M, Kume K, Robinson ME, Saravanakumar S, Lenz G, Chen Z, Song JY, Siddiqi T, Oksa L, Knapp AM, Cutler J, Cosgun KN, Klemm L, Ecker V, Winchester J, Ghergus D, Soulas-Sprauel P, Kiefer F, Heisterkamp N, Pandey A, Ngo V, Wang L, Jumaa H, Buchner M, Ruland J, Chan WC, Meffre E, Martin T, Müschen M. Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer. Molecular Cell 2021, 81: 2094-2111.e9. PMID: 33878293, PMCID: PMC8239336, DOI: 10.1016/j.molcel.2021.03.043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19AutoimmunityB-LymphocytesCalciumCell DifferentiationCell Transformation, NeoplasticEnzyme ActivationHumansImmune ToleranceLymphoma, B-CellMiceModels, GeneticNeoplasm ProteinsNeoplasmsNFATC Transcription FactorsPhosphatidylinositol 3-KinasesProtein BindingReceptors, Antigen, B-CellSignal TransductionSyk KinaseZAP-70 Protein-Tyrosine Kinase
2020
IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells
Lee J, Robinson ME, Ma N, Artadji D, Ahmed MA, Xiao G, Sadras T, Deb G, Winchester J, Cosgun KN, Geng H, Chan LN, Kume K, Miettinen TP, Zhang Y, Nix MA, Klemm L, Chen CW, Chen J, Khairnar V, Wiita AP, Thomas-Tikhonenko A, Farzan M, Jung JU, Weinstock DM, Manalis SR, Diamond MS, Vaidehi N, Müschen M. IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells. Nature 2020, 588: 491-497. PMID: 33149299, PMCID: PMC8087162, DOI: 10.1038/s41586-020-2884-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19B-LymphocytesCell Transformation, NeoplasticFemaleGerminal CenterHumansIntegrinsMembrane MicrodomainsMembrane ProteinsMiceMice, Inbred C57BLMice, Inbred NODModels, MolecularPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphorylationReceptors, Antigen, B-CellRNA-Binding ProteinsSignal TransductionConceptsPI3KCell leukemiaAntiviral effector functionsAntigen-specific antibodiesInterferon-induced transmembrane proteinsIFITM3 functionDevelopment of leukemiaCell surfacePoor outcomeOncogenic PI3KClinical cohortEffector functionsGerminal centersMouse modelB cellsExpression of IFITM3Malignant transformationAccumulation of PIP3PI3K signalsCell receptorNormal numbersLeukemiaDefective expressionEndosomal proteinIFITM3
2013
Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia
Gang EJ, Hsieh YT, Pham J, Zhao Y, Nguyen C, Huantes S, Park E, Naing K, Klemm L, Swaminathan S, Conway EM, Pelus LM, Crispino J, Mullighan CG, McMillan M, Müschen M, Kahn M, Kim YM. Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia. Oncogene 2013, 33: 2169-2178. PMID: 23728349, PMCID: PMC3994178, DOI: 10.1038/onc.2013.169.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAsparaginasebeta CateninBridged Bicyclo Compounds, HeterocyclicCell Line, TumorCell ProliferationCell SurvivalDexamethasoneDown-RegulationDrug Resistance, NeoplasmDrug SynergismHumansInhibitor of Apoptosis ProteinsMiceMice, Inbred NODMice, SCIDMutationPeptide FragmentsPrecursor Cell Lymphoblastic Leukemia-LymphomaPyrimidinonesSialoglycoproteinsSurvivinVincristineWnt Signaling PathwayXenograft Model Antitumor AssaysConceptsICG-001Activation of genesDivergent cellular responsesProgenitor cellsInitiation of differentiationSmall molecule modulatorsAcute lymphoblastic leukemiaAmino acids 1Small molecule inhibitionWnt/cateninNovel small molecule modulatorsPrimary acute lymphoblastic leukemiaCoactivator CBPChromatin immunoprecipitationTranscriptional activationHematopoietic progenitor cellsSelf-renewal capacityApoptosis proteinNormal hematopoietic progenitor cellsCBP mutationsN-terminusCellular responsesC-terminalCatenin interactionSurvivin promoter
2012
Vitamin D protects acute lymphoblastic leukemia cells from dexamethasone.
Antony R, Sheng X, Ehsanipour EA, Ng E, Pramanik R, Klemm L, Ichihara B, Mittelman SD. Vitamin D protects acute lymphoblastic leukemia cells from dexamethasone. Leukemia Research 2012, 36: 591-3. PMID: 22341429, PMCID: PMC3312954, DOI: 10.1016/j.leukres.2012.01.011.Peer-Reviewed Original Research
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Müschen Lab
300 George Street, Room 862
New Haven, CT 06511
United States