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
2023
Decoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinoma
Ruiz C, Garcia C, Jacox J, Lawres L, Muzumdar M. Decoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinoma. Life Science Alliance 2023, 6: e202302228. PMID: 37648285, PMCID: PMC10474221, DOI: 10.26508/lsa.202302228.Peer-Reviewed Original ResearchConceptsPancreatic adenocarcinomaPreclinical modelsObesity-cancer connectionObesity-associated cancersMicrobial dysbiosisHormone dysregulationEarly progressionRisk factorsWorldwide prevalencePancreatic tumorigenesisObesityPreclinical modelingCancer typesCancer developmentTumor cellsAdenocarcinomaTumor initiationCancerMetabolic stateCellular metabolismNovel strategyDysbiosisInflammationTherapyPrevalenceIntegrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases: Workshop Proceedings.
Mastracci T, Apte M, Amundadottir L, Alvarsson A, Artandi S, Bellin M, Bernal-Mizrachi E, Caicedo A, Campbell-Thompson M, Cruz-Monserrate Z, El Ouaamari A, Gaulton K, Geisz A, Goodarzi M, Hara M, Hull-Meichle R, Kleger A, Klein A, Kopp J, Kulkarni R, Muzumdar M, Naren A, Oakes S, Olesen S, Phelps E, Powers A, Stabler C, Tirkes T, Whitcomb D, Yadav D, Yong J, Zaghloul N, Pandol S, Sander M. Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases: Workshop Proceedings. Diabetes 2023, 72: 433-448. PMID: 36940317, PMCID: PMC10033248, DOI: 10.2337/db22-0942.Peer-Reviewed Original ResearchConceptsPancreatic diseaseEndocrine compartmentExocrine diseaseBasic science investigatorsExocrine disorderIntegrated physiologyMetabolic influencesExocrine pancreasDiseaseDisease mechanismsNormal physiologyNational InstitutePancreas anatomyGenetic driversPancreasMultiple presentationsExocrineCurrent knowledge
2022
Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases
Mastracci T, Apte M, Amundadottir L, Alvarsson A, Artandi S, Bellin M, Bernal-Mizrachi E, Caicedo A, Campbell-Thompson M, Cruz-Monserrate Z, Ouaamari A, Gaulton K, Geisz A, Goodarzi M, Hara M, Hull-Meichle R, Kleger A, Klein A, Kopp J, Kulkarni R, Muzumdar M, Naren A, Oakes S, Olesen S, Phelps E, Powers A, Stabler C, Tirkes T, Whitcomb D, Yadav D, Yong J, Zaghloul N, Sander M, Pandol S. Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases. Pancreas 2022, 51: 1061-1073. PMID: 37078927, PMCID: PMC10328394, DOI: 10.1097/mpa.0000000000002170.Peer-Reviewed Original Research
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: e106065. 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
Differences 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
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