Featured Publications
Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma
Chung KM, Singh J, Lawres L, Dorans KJ, Garcia C, Burkhardt DB, Robbins R, Bhutkar A, Cardone R, Zhao X, Babic A, Vayrynen SA, Dias Costa A, Nowak JA, Chang DT, Dunne RF, Hezel AF, Koong AC, Wilhelm JJ, Bellin MD, Nylander V, Gloyn AL, McCarthy MI, Kibbey RG, Krishnaswamy S, Wolpin BM, Jacks T, Fuchs CS, Muzumdar MD. Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma. Cell 2020, 181: 832-847.e18. PMID: 32304665, PMCID: PMC7266008, DOI: 10.1016/j.cell.2020.03.062.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell LineCell Line, TumorCell Transformation, NeoplasticDisease Models, AnimalDisease ProgressionEndocrine CellsExocrine GlandsFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, Inbred C57BLMutationObesityPancreatic NeoplasmsSignal TransductionTumor MicroenvironmentConceptsPancreatic ductal adenocarcinomaPDAC progressionDuctal adenocarcinomaMajor modifiable risk factorModifiable risk factorsBeta cell expressionObesity-associated changesAutochthonous mouse modelPancreatic ductal tumorigenesisDriver gene mutationsPeptide hormone cholecystokininRisk factorsPDAC developmentMouse modelObesityHormone cholecystokininOncogenic KrasCell expressionTumor microenvironmentDietary inductionCancer developmentGene mutationsReversible roleMurine samplesProgression
2024
Keep It Moving: Physical Activity in the Prevention of Obesity-Driven Pancreatic Cancer.
Sogunro A, Muzumdar M. Keep It Moving: Physical Activity in the Prevention of Obesity-Driven Pancreatic Cancer. Cancer Research 2024, 84: 2935-2937. PMID: 39279380, DOI: 10.1158/0008-5472.can-24-1474.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTumor microenvironmentAntitumor effectPancreatic cancerObese micePhysical activityAdvanced tumor growthSystemic cytokine productionMyeloid cell infiltrationPancreatic ductal adenocarcinoma developmentEffect of obesityHigh-fat diet-induced obesityDiet-induced obesitySyngeneic allograftsAdvanced tumorsProtumorigenic effectsLean miceWhite adipose tissueCell infiltrationDuctal adenocarcinomaObesity-associatedTumor growthCytokine productionImpact of physical activityInflammatory cytokines
2021
5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING
Tian J, Zhang D, Kurbatov V, Wang Q, Wang Y, Fang D, Wu L, Bosenberg M, Muzumdar MD, Khan S, Lu Q, Yan Q, Lu J. 5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING. The EMBO Journal 2021, 40: embj2020106065. PMID: 33615517, PMCID: PMC8013832, DOI: 10.15252/embj.2020106065.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityTumor burdenSubsequent type I interferon productionHigh STING expressionIntratumoral T cellsT-cell depletionType I interferon productionI interferon productionLoss of STINGImmunocompetent hostsColorectal specimensT cellsSTING expressionBetter survivalHigh doseTherapeutic effectivenessHuman colorectal specimensMelanoma tumorsInterferon productionChemotherapeutic drugsMurine colonImmunityEfficacyStingsColon
2019
Identification of DHODH as a therapeutic target in small cell lung cancer
Li L, Ng SR, Colón CI, Drapkin BJ, Hsu PP, Li Z, Nabel CS, Lewis CA, Romero R, Mercer KL, Bhutkar A, Phat S, Myers DT, Muzumdar MD, Westcott PMK, Beytagh MC, Farago AF, Vander Heiden MG, Dyson NJ, Jacks T. Identification of DHODH as a therapeutic target in small cell lung cancer. Science Translational Medicine 2019, 11 PMID: 31694929, PMCID: PMC7401885, DOI: 10.1126/scitranslmed.aaw7852.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsBiphenyl CompoundsCarcinoma, Pancreatic DuctalCell Line, TumorDCMP DeaminaseDihydroorotate DehydrogenaseDisease ProgressionEnzyme InhibitorsHumansLung NeoplasmsMiceMolecular Targeted TherapyOxidoreductases Acting on CH-CH Group DonorsPancreatic NeoplasmsPyrimidinesSmall Cell Lung CarcinomaSurvival AnalysisXenograft Model Antitumor AssaysConceptsSmall cell lung cancerCell lung cancerPancreatic ductal adenocarcinomaLung cancerLung adenocarcinomaMouse modelSCLC cellsTherapeutic targetHuman patient-derived xenograft modelsAggressive lung cancer subtypePatient-derived xenograft modelsLung cancer subtypesAutochthonous mouse modelPotential therapeutic targetSCLC tumor growthGenetic driver eventsTreatment landscapePoor prognosisDuctal adenocarcinomaXenograft modelCancer subtypesTumor growthPharmacological inhibitionDihydroorotate dehydrogenaseGenetic vulnerability
2018
iRGD-guided tumor-penetrating nanocomplexes for therapeutic siRNA delivery to pancreatic cancer
Lo JH, Hao L, Muzumdar MD, Raghavan S, Kwon EJ, Pulver EM, Hsu F, Aguirre AJ, Wolpin BM, Fuchs CS, Hahn WC, Jacks T, Bhatia SN. iRGD-guided tumor-penetrating nanocomplexes for therapeutic siRNA delivery to pancreatic cancer. Molecular Cancer Therapeutics 2018, 17: molcanther.1090.2017. PMID: 30097486, PMCID: PMC6298224, DOI: 10.1158/1535-7163.mct-17-1090.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPancreatic cancerCancer-related deathReceptor expression patternsSite of diseasePDAC cell linesMol Cancer TherTherapeutic trialsAutochthonous tumorsDuctal adenocarcinomaMouse modelStromal barrierTumor growthSystemic deliveryNeuropilin-1Peptide iRGDTumor-penetrating abilityThree-dimensional organoidsSiRNATumor targetingCell linesTherapyCancerStromaIRGDDifferences in Nanoparticle Uptake in Transplanted and Autochthonous Models of Pancreatic Cancer
Tao Z, Muzumdar MD, Detappe A, Huang X, Xu ES, Yu Y, Mouhieddine TH, Song H, Jacks T, Ghoroghchian PP. Differences in Nanoparticle Uptake in Transplanted and Autochthonous Models of Pancreatic Cancer. Nano Letters 2018, 18: 2195-2208. PMID: 29533667, PMCID: PMC5957485, DOI: 10.1021/acs.nanolett.7b04043.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaHuman pancreatic ductal adenocarcinomaPancreatic tumorsMouse modelAutochthonous modelPoor overall prognosisAutochthonous mouse modelAutochthonous tumor modelTumor cell clustersOverall prognosisSurvival outcomesPancreatic cancerDuctal adenocarcinomaTransplanted tumorPreclinical studiesFree drug formulationDense stromaPreclinical testingTumor modelTumorsOxaliplatinNoninvasive optical imagingAnticancer agentsAnticancer drugsTherapeutic formulationsAdaptive and Reversible Resistance to Kras Inhibition in Pancreatic Cancer Cells
Chen PY, Muzumdar M, Dorans KJ, Robbins R, Bhutkar A, Del Rosario A, Mertins P, Qiao J, Schafer AC, Gertler F, Carr S, Jacks T. Adaptive and Reversible Resistance to Kras Inhibition in Pancreatic Cancer Cells. Cancer Research 2018, 78: 985-1002. PMID: 29279356, PMCID: PMC5837062, DOI: 10.1158/0008-5472.can-17-2129.Peer-Reviewed Original ResearchConceptsMurine PDAC cellsPDAC cellsNontranscriptional mechanismsKRAS inhibitorsGlobal phosphoproteomic profilingActivated KRASHallmark genetic alterationsTranscriptional changesPhosphoproteomic profilingCell signalingCell statesPathway componentsTumor-initiating capacityPancreatic ductal adenocarcinomaTemporal controlGenetic alterationsCell morphologyMechanistic directionsKras expressionKrasCellsProliferative kineticsInhibitorsNovel KRAS inhibitorsAdherence properties
2017
Survival of pancreatic cancer cells lacking KRAS function
Muzumdar MD, Chen PY, Dorans KJ, Chung KM, Bhutkar A, Hong E, Noll EM, Sprick MR, Trumpp A, Jacks T. Survival of pancreatic cancer cells lacking KRAS function. Nature Communications 2017, 8: 1090. PMID: 29061961, PMCID: PMC5653666, DOI: 10.1038/s41467-017-00942-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBenzimidazolesCarcinoma, Pancreatic DuctalDNA Copy Number VariationsHumansImmunoblottingIndazolesMiceMorpholinesPancreatic NeoplasmsPhenylurea CompoundsPiperidinesProto-Oncogene MasProto-Oncogene Proteins p21(ras)PurinesPyrimidinesPyrimidinonesQuinazolinonesSulfonamidesThiazolesConceptsMitogen-activated protein kinasePDAC cellsCRISPR/Cas-mediated genome editingDependent mitogen-activated protein kinaseKRAS inhibitionGene expression profilesMetastasis-related genesProto-oncogene KRASGenome editingProtein kinasePI3K inhibitorsExpression profilesDeficient cellsPancreatic cancer cellsMechanisms of responsePDAC resistanceKRAS functionInduced sensitivityPancreatic ductal adenocarcinomaRole of KRASK inhibitorsCancer cellsKRAS inhibitorsAbsolute dependenceSubset of humansEarly tumor detection afforded by in vivo imaging of near-infrared II fluorescence
Tao Z, Dang X, Huang X, Muzumdar MD, Xu ES, Bardhan NM, Song H, Qi R, Yu Y, Li T, Wei W, Wyckoff J, Birrer MJ, Belcher AM, Ghoroghchian PP. Early tumor detection afforded by in vivo imaging of near-infrared II fluorescence. Biomaterials 2017, 134: 202-215. PMID: 28482280, DOI: 10.1016/j.biomaterials.2017.04.046.Peer-Reviewed Original ResearchConceptsExogenous contrast agentsLanthanide nanoparticlesUnique nanoparticlesBiodegradable diblock copolymerRed fluorescent proteinOptical signalNIR-IINanoparticlesOVCAR-8 ovarian cancer cellsTumor accumulationTissue autofluorescenceOrganic fluorophoresContrast agentsTissue penetrationEarly tumor detectionFluorescent agentsOptical excitationEnhanced sensitivityIntrinsic reporterFluorescent proteinAccurate detectionNIRTumor detectionLuciferaseDiblock copolymers
2016
Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers
Muzumdar MD, Dorans KJ, Chung KM, Robbins R, Tammela T, Gocheva V, Li CM, Jacks T. Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers. Nature Communications 2016, 7: 12685. PMID: 27585860, PMCID: PMC5025814, DOI: 10.1038/ncomms12685.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell ProliferationCyclin-Dependent Kinase Inhibitor p16Disease ProgressionGene Expression Regulation, NeoplasticLung NeoplasmsMiceMice, TransgenicPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)Tumor Cells, CulturedTumor Suppressor Protein p53ConceptsLung adenomasLow-grade pancreatic intraepithelial neoplasiaP53 lossEarly tumor progressionPancreatic intraepithelial neoplasiaAdvanced adenocarcinomaIntraepithelial neoplasiaPancreatic tumorsP53 knockoutSolid tumorsOncogenic KrasTumor progressionSuppressive roleTumor developmentExtensive cellular heterogeneityLineage-related cellsP53AdenomasTumorsCancerContiguous growthDouble markersProgressionDistinct clonesDifferential expression
2013
Targeting the HGF/c-MET Pathway in Hepatocellular Carcinoma
Goyal L, Muzumdar MD, Zhu AX. Targeting the HGF/c-MET Pathway in Hepatocellular Carcinoma. Clinical Cancer Research 2013, 19: 2310-2318. PMID: 23388504, PMCID: PMC4583193, DOI: 10.1158/1078-0432.ccr-12-2791.Peer-Reviewed Original ResearchConceptsAdvanced hepatocellular carcinomaHepatocellular carcinomaRational clinical trial designC-MetHGF/c-Met pathwayTyrosine kinase inhibitor sorafenibLimited survival benefitMajority of patientsCancer-related morbidityPathogenesis of HCCLatest clinical trialsKinase inhibitor sorafenibC-Met pathwayClinical trial designAdvanced diseaseLiver transplantationSurgical resectionSurvival benefitSystemic therapyLocal therapyTransarterial embolizationPreclinical dataClinical trialsInhibitor sorafenibTrial design
2007
A global double‐fluorescent Cre reporter mouse
Muzumdar MD, Tasic B, Miyamichi K, Li L, Luo L. A global double‐fluorescent Cre reporter mouse. Genesis 2007, 45: 593-605. PMID: 17868096, DOI: 10.1002/dvg.20335.Peer-Reviewed Original ResearchModeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM)
Muzumdar MD, Luo L, Zong H. Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM). Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 4495-4500. PMID: 17360552, PMCID: PMC1810340, DOI: 10.1073/pnas.0606491104.Peer-Reviewed Original ResearchConceptsTumor suppressor geneHuman cancersDouble markersCyclin-dependent kinase inhibitorLoss of heterozygositySporadic lossKinase inhibitorsMiceSporadic cellsSimilar degreeSomatic activationCancerCell-autonomous controlConcurrent labelingTSG lossCell expansionMarkersCellsProof of principleProtooncogeneMosaic analysisTSG function
2005
Mosaic Analysis with Double Markers in Mice
Zong H, Espinosa JS, Su HH, Muzumdar MD, Luo L. Mosaic Analysis with Double Markers in Mice. Cell 2005, 121: 479-492. PMID: 15882628, DOI: 10.1016/j.cell.2005.02.012.Peer-Reviewed Original ResearchConceptsInterchromosomal recombinationCerebellar granule cell progenitorsGranule cell progenitorsHomologous chromosomesMosaic analysisChimeric geneSomatic cellsAxonal projectionsC-terminusGene knockoutCell lineagesN-terminusPostmitotic cellsGranule cellsCerebellar cortexNeuronal connectionsFunctional expressionCell progenitorsDouble markersConditional knockoutSmall populationSingle cellsSpecific sublayersTerminusMarkers