2024
The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia
Liu M, Ren Y, Zhou Z, Yang J, Shi X, Cai Y, Arreola A, Luo W, Fung K, Xu C, Nipp R, Bronze M, Zheng L, Li Y, Houchen C, Zhang Y, Li M. The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia. Cancer Cell 2024, 42: 885-903.e4. PMID: 38608702, PMCID: PMC11162958, DOI: 10.1016/j.ccell.2024.03.009.Peer-Reviewed Original ResearchConceptsPancreatic cancer cachexiaTumor cellsCancer cachexiaTherapeutic targetLimited treatment optionsPancreatic cancer cellsImmune microenvironmentCCL2/CCR2 axisPotential therapeutic targetTreatment optionsMuscle wastingReprogram macrophagesTumorMuscle atrophyCachexiaCancer cellsMacrophagesNon-autonomous activationMuscle remodelingCancerMuscle degradationSecretionCellsMuscleTWEAK
2023
Absence of either Ripk3 or Mlkl reduces incidence of hepatocellular carcinoma independent of liver fibrosis
Mohammed S, Thadathil N, Ohene-Marfo P, Tran A, Van Der Veldt M, Georgescu C, Oh S, Nicklas E, Wang D, Haritha N, Luo W, Janknecht R, Miller B, Wren J, Freeman W, Deepa S. Absence of either Ripk3 or Mlkl reduces incidence of hepatocellular carcinoma independent of liver fibrosis. Molecular Cancer Research 2023, 21: 933-946. PMID: 37204757, PMCID: PMC10472095, DOI: 10.1158/1541-7786.mcr-22-0820.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseProgression of NAFLDHepatocellular carcinomaChronic inflammationLiver fibrosisMale miceMouse modelCholine-deficient high-fat dietFemale wild-type miceOncogenic pathwaysFatty liver diseaseMarkers of inflammationHigh-fat dietLow-fat dietDevelopment of inflammationValid therapeutic targetWild-type miceHepatic inflammationInflammation contributesLiver diseaseWT miceFemale miceSex-specific differencesInflammationTherapeutic targetCombining ASBT inhibitor and FGF15 treatments enhances therapeutic efficacy against cholangiopathy in female but not male Cyp2c70 KO mice
Hasan M, Chen J, Matye D, Wang H, Luo W, Gu L, Clayton Y, Du Y, Li T. Combining ASBT inhibitor and FGF15 treatments enhances therapeutic efficacy against cholangiopathy in female but not male Cyp2c70 KO mice. Journal Of Lipid Research 2023, 64: 100340. PMID: 36737039, PMCID: PMC9986646, DOI: 10.1016/j.jlr.2023.100340.Peer-Reviewed Original ResearchConceptsBile acid poolKO miceTherapeutic efficacyHepatobiliary injuryBile acid pool sizeBile acid exposureGut barrier integrityGut barrier functionBile acid metabolismAcid poolBile acid synthesisAcid pool sizeBile acid uptakePortal inflammationPortal fibrosisGut exposureDuctular reactionGSK2330672Therapeutic reductionUrsodeoxycholic acidMuricholic acidAcid exposureASBT inhibitorSevere cholangiopathyBarrier integrity
2022
17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice
Ali Mondal S, Sathiaseelan R, Mann S, Kamal M, Luo W, Saccon T, Isola J, Peelor F, Li T, Freeman W, Miller B, Stout M. 17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice. AJP Endocrinology And Metabolism 2022, 324: e120-e134. PMID: 36516471, PMCID: PMC9902223, DOI: 10.1152/ajpendo.00256.2022.Peer-Reviewed Original ResearchConceptsLiver fibrosisMale miceCombination hormone replacement therapyMatrix metalloproteinase-2 activityHepatic stellate cell activationChronic liver diseaseHormone replacement therapySubset of womenMetalloproteinase-2 activityStellate cell activationGrowth factor-β1Proinflammatory macrophage activationFibrotic burdenCollagen synthesis ratesChronic treatmentLiver diseaseReplacement therapyCytokine expressionMacrophage contentImmune cellsTGF-β1Estrogen signalingHSC activationFactor-β1Macrophage activationmiR-130b/301b Is a Negative Regulator of Beige Adipogenesis and Energy Metabolism In Vitro and In Vivo.
Luo W, Kim Y, Jensen M, Herlea-Pana O, Wang W, Rudolph M, Friedman J, Chernausek S, Jiang S. miR-130b/301b Is a Negative Regulator of Beige Adipogenesis and Energy Metabolism In Vitro and In Vivo. Diabetes 2022, 71: 2360-2371. PMID: 36001751, PMCID: PMC9630090, DOI: 10.2337/db22-0205.Peer-Reviewed Original ResearchConceptsBeige adipogenesisMiR-301bMiR-130bPeroxisome proliferator-activated receptor γ coactivator 1αProliferator-activated receptor γ coactivator 1αImproved glucose toleranceReceptor γ coactivator 1αLess weight gainPotential therapeutic targetCold-induced energy expenditureΓ coactivator 1αMitochondrial biogenesisMetabolic complicationsVisceral adiposityGlucose toleranceThermogenic brownCounteract obesityMetabolic disordersTherapeutic targetAdipose tissueBeige phenotypeMetabolic diseasesAdipose progenitor cellsBeige adipocytesCoactivator 1αSenolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma
Thadathil N, Selvarani R, Mohammed S, Nicklas E, Tran A, Kamal M, Luo W, Brown J, Lawrence M, Borowik A, Miller B, Van Remmen H, Richardson A, Deepa S. Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma. Aging Cell 2022, 21: e13676. PMID: 35869934, PMCID: PMC9381894, DOI: 10.1111/acel.13676.Peer-Reviewed Original ResearchConceptsSod1KO miceHepatocellular carcinomaQ treatmentCellular senescenceSenescence-associated secretory phenotype factorsMarkers of necroptosisSod1 knockout miceChronic liver diseaseMarkers of inflammationMonths of ageExpression of p16WT levelsSenolytic treatmentLiver diseaseReduced inflammationCu/Zn-superoxide dismutaseMacrophage levelsLiver fibrosisPhenotype factorsLiver cancerNecrostatin-1sKnockout miceAge-associated pathologiesMice nullInflammationAcetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis and Muscle Wasting Through Metabolic Reprogramming in Pancreatic Cancer
Zhou Z, Ren Y, Yang J, Liu M, Shi X, Luo W, Fung K, Xu C, Bronze M, Zhang Y, Houchen C, Li M. Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis and Muscle Wasting Through Metabolic Reprogramming in Pancreatic Cancer. Gastroenterology 2022, 163: 1281-1293.e1. PMID: 35777482, PMCID: PMC9613512, DOI: 10.1053/j.gastro.2022.06.058.Peer-Reviewed Original ResearchConceptsMetabolic reprogrammingDynamin 2Transcriptional activationShort palindromic repeat-associated protein 9 (CRISPR/Cas9) systemSingle-cell RNA sequencing dataRNA sequencing dataProtein 9 (Cas9) systemGlycogen synthase kinasePancreatic cancerEpigenetic reprogrammingFamily member 2Chromatin immunoprecipitationMuscle wastingDownstream targetsSequencing dataSyndecan-1ReprogrammingSynthase kinaseWorse prognosisMacropinocytosisZIP4ACSS2Mouse modelProtein 4Uptake assaysCircular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2–AKT–TGF-β Signaling Axis in Pancreatic Cancer
Shi X, Yang J, Liu M, Zhang Y, Zhou Z, Luo W, Fung K, Xu C, Bronze M, Houchen C, Li M. Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2–AKT–TGF-β Signaling Axis in Pancreatic Cancer. Gastroenterology 2022, 162: 2004-2017.e2. PMID: 35176309, PMCID: PMC10428768, DOI: 10.1053/j.gastro.2022.02.017.Peer-Reviewed Original ResearchConceptsZinc-dependent transcription factorsFunction of circRNAsMiR-373Dephosphorylation of AktDephosphorylation of CREBNovel tumor suppressorCyclin D1Feed-forward loopMouse skeletal muscleHuman pancreatic cancer cellsRNA interactionsTumor growthTranscription factorsCircular RNAsPancreatic cancer progressionMuscle wastingAkt dephosphorylationRNA immunoprecipitationCancer cell proliferationDownstream targetsPancreatic cancer cellsTumor suppressorSilico analysisPancreatic cancerSignaling Axis
2021
Combined ASBT Inhibitor and FGF15 Treatment Improves Therapeutic Efficacy in Experimental Nonalcoholic Steatohepatitis
Matye D, Wang H, Luo W, Sharp R, Chen C, Gu L, Jones K, Ding W, Friedman J, Li T. Combined ASBT Inhibitor and FGF15 Treatment Improves Therapeutic Efficacy in Experimental Nonalcoholic Steatohepatitis. Cellular And Molecular Gastroenterology And Hepatology 2021, 12: 1001-1019. PMID: 33965587, PMCID: PMC8346663, DOI: 10.1016/j.jcmgh.2021.04.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsCholesterolCombined Modality TherapyDependovirusDisease Models, AnimalFibroblast Growth FactorsFructoseGene Expression ProfilingGene Expression RegulationGenetic TherapyGenetic VectorsMaleMethylaminesMiceNon-alcoholic Fatty Liver DiseaseThiazepinesTreatment OutcomeConceptsNonalcoholic steatohepatitisBile acid synthesisTherapeutic efficacyFGF19 analogueASBT inhibitorTreatment-associated adverse eventsFecal bile acid excretionASBT inhibitionDiet-induced nonalcoholic steatohepatitisHepatic bile acid synthesisWeight lossBile acid excretionGrowth factor 15Experimental nonalcoholic steatohepatitisDiet-fed miceFurther clinical studiesNew treatment strategiesIntestinal lipid absorptionAdverse eventsAdipose inflammationMetabolic improvementTreatment attenuatesLipid malabsorptionClinical findingsTreatment strategiesZinc-Dependent Regulation of ZEB1 and YAP1 Coactivation Promotes Epithelial-Mesenchymal Transition Plasticity and Metastasis in Pancreatic Cancer
Liu M, Zhang Y, Yang J, Zhan H, Zhou Z, Jiang Y, Shi X, Fan X, Zhang J, Luo W, Fung K, Xu C, Bronze M, Houchen C, Li M. Zinc-Dependent Regulation of ZEB1 and YAP1 Coactivation Promotes Epithelial-Mesenchymal Transition Plasticity and Metastasis in Pancreatic Cancer. Gastroenterology 2021, 160: 1771-1783.e1. PMID: 33421513, PMCID: PMC8035249, DOI: 10.1053/j.gastro.2020.12.077.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCation Transport ProteinsCell Line, TumorCell MovementCell PlasticityEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansIntegrin alpha3MiceMicroRNAsNeoplasm InvasivenessNeoplasm MetastasisPancreatic NeoplasmsSignal TransductionSpheroids, CellularTranscription FactorsYAP-Signaling ProteinsZincZinc Finger E-box-Binding Homeobox 1ConceptsEMT plasticityHuman pancreatic cancer cellsPancreatic cancer cellsZinc-dependent regulationHippo pathway effector YAP1Cancer cellsMiR-373Zinc transporter ZIP4Potent transcriptional coactivatorMesenchymal-epithelial transition (MET) statesAssociate domainTranscriptional regulationChromatin immunoprecipitationEffector YAP1Transcriptional coactivatorYAP1/Downstream targetsPancreatic cancer metastasisMouse cellsMolecular eventsZIP4YAP1Cell adhesionLuciferase reporterSpontaneous mouse model
2017
HuR promotes the molecular signature and phenotype of activated microglia: Implications for amyotrophic lateral sclerosis and other neurodegenerative diseases
Matsye P, Zheng L, Si Y, Kim S, Luo W, Crossman D, Bratcher P, King P. HuR promotes the molecular signature and phenotype of activated microglia: Implications for amyotrophic lateral sclerosis and other neurodegenerative diseases. Glia 2017, 65: 945-963. PMID: 28300326, PMCID: PMC7944581, DOI: 10.1002/glia.23137.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisNeurodegenerative diseasesIL-1βLateral sclerosisALS spinal cordMutant SOD1 micePossible therapeutic targetTranscription factor NF-κBLipopolysaccharide-induced IL-1βFactor NF-κBMolecular signaturesRole of HuRLuciferase reporter studiesActivated microgliaProinflammatory factorsSOD1 miceIL-6Inflammatory pathwaysMicroglial migrationImmune cellsSpinal cordChronic activationMicrogliaNF-κBTherapeutic target
2014
Hu Antigen R (HuR) Is a Positive Regulator of the RNA-binding Proteins TDP-43 and FUS/TLS Implications for Amyotrophic Lateral Sclerosis*
Lu L, Zheng L, Si Y, Luo W, Dujardin G, Kwan T, Potochick N, Thompson S, Schneider D, King P. Hu Antigen R (HuR) Is a Positive Regulator of the RNA-binding Proteins TDP-43 and FUS/TLS Implications for Amyotrophic Lateral Sclerosis*. Journal Of Biological Chemistry 2014, 289: 31792-31804. PMID: 25239623, PMCID: PMC4231657, DOI: 10.1074/jbc.m114.573246.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAmyotrophic Lateral SclerosisAnimalsAstrocytesCell LineCell Line, TumorCell SurvivalCulture Media, ConditionedCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsELAV ProteinsELAV-Like Protein 1Gene Expression RegulationHumansHypoxiaMiceMotor NeuronsPhenotypeRNARNA-Binding Protein FUSConceptsAmyotrophic lateral sclerosis
2009
Identification of exopolysaccharide‐deficient mutants of Mycoplasma pulmonis
Daubenspeck J, Bolland J, Luo W, Simmons W, Dybvig K. Identification of exopolysaccharide‐deficient mutants of Mycoplasma pulmonis. Molecular Microbiology 2009, 72: 1235-1245. PMID: 19432800, PMCID: PMC2752295, DOI: 10.1111/j.1365-2958.2009.06720.x.Peer-Reviewed Original ResearchConceptsOpen reading frameExopolysaccharide-deficient mutantsSynthesis of exopolysaccharidesTerminal beta-linked galactose residuesA549 lung cell lineHeterodimeric pairTransposon librarySecond exopolysaccharideReading frameMutantsPhenotypic analysisLung cell linesDecreased associationN-acetylglucosamineCell linesExopolysaccharideCapsular exopolysaccharideLectin affinity chromatographyGalactose residuesComplex carbohydratesNew pathwayPermeasesMouse lungMollicutesTransposon
2008
Association of Mycoplasma arthritidis Mitogen with Lethal Toxicity but Not with Arthritis in Mice
Luo W, Yu H, Cao Z, Schoeb T, Marron M, Dybvig K. Association of Mycoplasma arthritidis Mitogen with Lethal Toxicity but Not with Arthritis in Mice. Infection And Immunity 2008, 76: 4989-4998. PMID: 18779340, PMCID: PMC2573368, DOI: 10.1128/iai.00667-08.Peer-Reviewed Original ResearchConceptsCBA/J miceLethal toxicityHuman rheumatoid arthritisSeverity of arthritisMycoplasma arthritidis mitogenChronic arthritisRheumatoid arthritisHistopathological studyJ miceSystemic injectionDBA/2J miceArthritisPathogenic significanceMiceMitogenic activityMycoplasma arthritidisToxicityAcutePathogenesisSuperantigensArthritogenicityDiseaseSeverity