Featured Publications
A precision medicine approach to metabolic therapy for breast cancer in mice
Akingbesote ND, Norman A, Zhu W, Halberstam AA, Zhang X, Foldi J, Lustberg MB, Perry RJ. A precision medicine approach to metabolic therapy for breast cancer in mice. Communications Biology 2022, 5: 478. PMID: 35595952, PMCID: PMC9122928, DOI: 10.1038/s42003-022-03422-9.Peer-Reviewed Original ResearchConceptsPrecision medicine approachBreast cancerSodium-glucose transport protein 2 inhibitorsBreast tumorsMedicine approachCanonical insulinSGLT2 inhibitor dapagliflozinEfficacy of paclitaxelBreast tumor-bearing miceTumor glucose uptakeTumor-bearing miceChemotherapy correlatesNeoadjuvant approachNeoadjuvant settingPaclitaxel chemotherapyInhibitor dapagliflozinSGLT2 inhibitorsProlonging survivalAntihyperglycemic drugsPotential adjuvantMetabolic therapyDapagliflozinTumorsDriver mutationsGlucose uptakeGene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo
Akingbesote N, Leitner B, Jovin D, Desrouleaux R, Owusu D, Zhu W, Li Z, Pollak M, Perry R. Gene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo. ELife 2023, 12: e78335. PMID: 37219930, PMCID: PMC10205083, DOI: 10.7554/elife.78335.Peer-Reviewed Original ResearchConceptsMetabolic scalingMetabolic fluxMetabolic processesBody sizeMitochondrial metabolic processesMultiple cellular compartmentsVivo metabolic fluxesLevel of genesKey metabolic pathwaysProtein expressionMetabolic flux analysisAspects of metabolismCellular compartmentsGene expressionDifferential expressionMetabolic pathwaysGenesFlux analysisOxidative damageEnzyme activitySubstrate supplyFold rangeSpeciesExpressionMetabolic rateIsotope tracing reveals distinct substrate preference in murine melanoma subtypes with differing anti-tumor immunity
Zhang X, Halberstam A, Zhu W, Leitner B, Thakral D, Bosenberg M, Perry R. Isotope tracing reveals distinct substrate preference in murine melanoma subtypes with differing anti-tumor immunity. Cancer & Metabolism 2022, 10: 21. PMID: 36457136, PMCID: PMC9714036, DOI: 10.1186/s40170-022-00296-7.Peer-Reviewed Original ResearchTumor microenvironmentAnti-tumor immunityPotential prognostic factorsObesity-associated cancersPotential prognostic predictorPatient RNA-seq dataSubset of studiesImmunogenic tumorsCancer Genome AtlasLymphocyte infiltrationMelanoma cell linesPrognostic factorsPrognostic predictorMetabolic therapyMelanoma subtypesMurine modelImmune functionMetabolic gene expressionMelanoma progressionMelanomaSubstrate metabolismMetabolic flux studiesGene expressionGenome AtlasCell linesDichloroacetate as a novel pharmaceutical treatment for cancer-related fatigue in melanoma
Zhang X, Lee W, Leitner B, Zhu W, Fosam A, Li Z, Gaspar R, Halberstam A, Robles B, Rabinowitz J, Perry R. Dichloroacetate as a novel pharmaceutical treatment for cancer-related fatigue in melanoma. AJP Endocrinology And Metabolism 2023, 325: e363-e375. PMID: 37646579, PMCID: PMC10642987, DOI: 10.1152/ajpendo.00105.2023.Peer-Reviewed Original ResearchConceptsCancer-related fatigueNovel pharmaceutical treatmentsPhysical functionPharmaceutical treatmentTumor growthCancer treatmentStandard cancer treatmentTumor-bearing miceLate-stage tumorsEffective pharmaceutical treatmentMurine cancer modelsNew metabolic targetsMultiple cancer typesAdjuvant therapyCommon complicationPatients' qualitySymptom managementClinical trialsMurine modelPotential therapyPharmaceutical therapySmall molecule inhibitorsCancer modelDCA treatmentLactate concentration
2024
Deficits in brain glucose transport among younger adults with obesity
Gunawan F, Matson B, Coppoli A, Jiang L, Ding Y, Perry R, Sanchez‐Rangel E, DeAguiar R, Behar K, Rothman D, Mason G, Hwang J. Deficits in brain glucose transport among younger adults with obesity. Obesity 2024, 32: 1329-1338. PMID: 38764181, DOI: 10.1002/oby.24034.Peer-Reviewed Original ResearchBrain glucose transportLean participantsMarkers of insulin resistanceMagnetic resonance spectroscopy scansEffect of obesityAssociated with alterationsLong-term brain functionCerebral glucose metabolic rateGlucose transportGlucose metabolic rateCardiometabolic comorbiditiesBrain energy utilizationPeripheral markersHyperglycemic clampInsulin resistanceObesityBrain glucose uptakeHuman findingsEating behaviorsYounger ageYoung healthy participantsNeurocognitive functionGlucose transport capacityBrain functionNonesterified fatty acidsFatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring
Sun J, Esplugues E, Bort A, Cardelo M, Ruz-Maldonado I, Fernández-Tussy P, Wong C, Wang H, Ojima I, Kaczocha M, Perry R, Suárez Y, Fernández-Hernando C. Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring. Nature Metabolism 2024, 6: 741-763. PMID: 38664583, DOI: 10.1038/s42255-024-01019-6.Peer-Reviewed Original ResearchConceptsFatty acid binding protein 5Tumor-associated macrophagesHepatocellular carcinomaImmunosuppressive phenotype of tumor-associated macrophagesIncreased CD8+ T cell activationCD8+ T cell activationPhenotype of tumor-associated macrophagesPro-inflammatory tumor microenvironmentCo-stimulatory molecules CD80T cell activationHepatocellular carcinoma burdenTransformation of hepatocytesBinding protein 5Potential therapeutic approachImmunosuppressive phenotypeTumor microenvironmentFerroptosis-induced cell deathMale miceEnhanced ferroptosisTherapeutic approachesPharmacological inhibitionGenetic ablationIncreased expressionSingle-cell atlasAnalysis of transformed cellsA new metabolic signature to predict melanoma recurrence
Vu N, Perry R. A new metabolic signature to predict melanoma recurrence. Clinical And Translational Discovery 2024, 4 DOI: 10.1002/ctd2.288.Commentaries, Editorials and LettersA New Mitochondrial Uncoupler Improves Metabolic Homeostasis in Mice.
Ramshankar G, Perry R. A New Mitochondrial Uncoupler Improves Metabolic Homeostasis in Mice. Diabetes 2024, 73: 357-358. PMID: 38377448, DOI: 10.2337/dbi23-0033.Commentaries, Editorials and LettersNovel muscle-derived extracellular matrix hydrogel promotes angiogenesis and neurogenesis in volumetric muscle loss
Chen Z, Huang Y, Xing H, Tseng T, Edelman H, Perry R, Kyriakides T. Novel muscle-derived extracellular matrix hydrogel promotes angiogenesis and neurogenesis in volumetric muscle loss. Matrix Biology 2024, 127: 38-47. PMID: 38325441, PMCID: PMC10958762, DOI: 10.1016/j.matbio.2024.02.001.Peer-Reviewed Original ResearchConceptsDecellularized extracellular matrixVolumetric muscle lossCharacterization of hydrogelsExtracellular matrix hydrogelTreat VML injuriesMuscle lossEnhancement of tissue repairRegenerative capacity of skeletal muscleMatrix hydrogelPromote muscle repairRegenerative capacityHydrogelsVolumetric muscle loss modelNative biomaterialsScar tissue formationEnhanced cell invasionCapacity of skeletal muscleMuscle repairTibialis anterior muscleClinical challengeBlood vessel formationReduce inflammationVML injuryLoss of functionSubcutaneous implantationThiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma
Zhang X, Gao Y, Tang K, Li Z, Halberstam A, Zhou L, Perry R. Thiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma. AJP Endocrinology And Metabolism 2024, 326: e341-e350. PMID: 38294697, DOI: 10.1152/ajpendo.00346.2023.Peer-Reviewed Original ResearchPD-1 expressionCD8+ T cellsT cell exhaustionPD-1T cellsImmunotherapy efficacyAnti-programmed cell death protein 1Tumor-infiltrating CD8+ T cellsAnti-PD-1 monoclonal antibodyAnti-PD-1 responseAnti-PD-1 treatmentCell death protein 1Enhance immunotherapy efficacyEnhance immunotherapy responseImprove immunotherapy efficacyEfficacy of immunotherapyMurine melanoma modelTumor-bearing miceExpression of peroxisome proliferator-activated receptor gammaOverall survival timePeroxisome proliferator-activated receptor gammaEffect of obesityProliferator-activated receptor gammaHuman T cellsTreated in vitroMetabolic underpinnings of cancer-related fatigue
Zhang X, Perry R. Metabolic underpinnings of cancer-related fatigue. AJP Endocrinology And Metabolism 2024, 326: e290-e307. PMID: 38294698, DOI: 10.1152/ajpendo.00378.2023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCancer-related fatigueMechanisms of cancer-related fatigueInsulin resistanceImpact of obesityCancer-induced painComplication of cancerTarget obesityInduce chronic inflammationObesityNarrative reviewObesity/insulin resistanceTumor growthChronic inflammationDetrimental complicationsCancer patientsMetabolic alterationsClinical researchNeuroendocrinological disturbancesMetabolic underpinningsAnalyzed recent studiesInsulinFatigueBehavioral disruptionPatientsPotential mechanisms
2023
Tissue-specific reprogramming of glutamine metabolism maintains tolerance to sepsis
Leitner B, Lee W, Zhu W, Zhang X, Gaspar R, Li Z, Rabinowitz J, Perry R. Tissue-specific reprogramming of glutamine metabolism maintains tolerance to sepsis. PLOS ONE 2023, 18: e0286525. PMID: 37410734, PMCID: PMC10325078, DOI: 10.1371/journal.pone.0286525.Peer-Reviewed Original ResearchConceptsTCA cycle anaplerosisGlobal mitochondrial dysfunctionAromatic amino acid transportAmino acid transportTissue-specific metabolic responsesMurine polymicrobial sepsis modelMetabolic signaturesAntioxidant metabolismGlutathione biosynthesisMitochondrial metabolismTCA cycleGreat therapeutic interestEnergetic demandsPolymicrobial sepsis modelAntioxidant synthesisUnique metabolic signatureGlutamine metabolismMitochondrial dysfunctionAcid transportMuscle transcriptomicsGlutathione cyclingATP ratioIsotope tracingCritical illnessReduced expressionA review of the impact of energy balance on triple-negative breast cancer
Akingbesote N, Owusu D, Liu R, Cartmel B, Ferrucci L, Zupa M, Lustberg M, Sanft T, Blenman K, Irwin M, Perry R. A review of the impact of energy balance on triple-negative breast cancer. JNCI Monographs 2023, 2023: 104-124. PMID: 37139977, DOI: 10.1093/jncimonographs/lgad011.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTriple-negative breast cancerInterventional studyBreast cancerCancer treatmentClinical interventional studyClinical observationalImmune activationCancer outcomesCancer careClinical studiesOverall healthEnergy intakeNarrative reviewCancer cellsEnergy expenditureCancerTreatmentEnergy balanceOutcomesExerciseReviewDetrimental effectsImmunotherapyStudyIntakeIt's Not Just for Pain: A New Metabolic Function of Aspirin
Perry R. It's Not Just for Pain: A New Metabolic Function of Aspirin. Endocrinology 2023, 164: bqad036. PMID: 36809391, DOI: 10.1210/endocr/bqad036.Peer-Reviewed Original Research
2022
Insulin and cancer: a tangled web
Leitner BP, Siebel S, Akingbesote ND, Zhang X, Perry RJ. Insulin and cancer: a tangled web. Biochemical Journal 2022, 479: 583-607. PMID: 35244142, PMCID: PMC9022985, DOI: 10.1042/bcj20210134.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAn optimized method for tissue glycogen quantification
Schaubroeck KJ, Leitner BP, Perry RJ. An optimized method for tissue glycogen quantification. Physiological Reports 2022, 10: e15195. PMID: 35179318, PMCID: PMC8855679, DOI: 10.14814/phy2.15195.Peer-Reviewed Original ResearchMultimodal analysis suggests differential immuno-metabolic crosstalk in lung squamous cell carcinoma and adenocarcinoma
Leitner BP, Givechian KB, Ospanova S, Beisenbayeva A, Politi K, Perry RJ. Multimodal analysis suggests differential immuno-metabolic crosstalk in lung squamous cell carcinoma and adenocarcinoma. Npj Precision Oncology 2022, 6: 8. PMID: 35087143, PMCID: PMC8795406, DOI: 10.1038/s41698-021-00248-2.Peer-Reviewed Original ResearchNon-small cell lung cancerLung squamous cell carcinomaBody mass indexSquamous cell carcinomaLung adenocarcinomaHigher glucose uptakeVisceral adiposityVisceral fatCell carcinomaLung cancerGlucose uptakeTreatment of NSCLCHigher body mass indexTumor-infiltrating T cellsImmune checkpoint inhibitionCell lung cancerHigh visceral fatPET/CT imagingTumors of patientsPrecision therapy approachesTumor glucose uptakePrecision medicine approachLUSC tumorsPrognostic gene expressionAdjunct therapy
2020
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis
Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis. Nature 2020, 579: 279-283. PMID: 32132708, PMCID: PMC7101062, DOI: 10.1038/s41586-020-2074-6.Peer-Reviewed Original ResearchConceptsHepatic steatosisType 2Nonalcoholic fatty liver diseaseDiet-induced hepatic steatosisFatty liver diseasePlasma glucagon concentrationsHepatic adipose triglyceride lipaseHepatic acetyl-CoA contentHepatic glucose productionRatio of insulinHepatic glucose metabolismInositol triphosphate receptorAdipose triglyceride lipaseMitochondrial oxidationMitochondrial fat oxidationGlucose intoleranceLiver diseaseGlucagon concentrationsInsulin resistancePortal veinAcetyl-CoA contentHepatic lipolysisGlucagon biologyGlucose metabolismKnockout miceThe Impact of Obesity on Tumor Glucose Uptake in Breast and Lung Cancer
Leitner BP, Perry RJ. The Impact of Obesity on Tumor Glucose Uptake in Breast and Lung Cancer. JNCI Cancer Spectrum 2020, 4: pkaa007. PMID: 32368718, PMCID: PMC7190208, DOI: 10.1093/jncics/pkaa007.Peer-Reviewed Original ResearchBody mass indexTumor glucose uptakeLung cancerGlucose uptakeGlucose metabolismNon-small cell lung cancerHigher body mass indexObesity-cancer linkImpact of obesityCell lung cancerSquamous cell carcinomaSoft tissue sarcomasAltered glucose metabolismPoor clinical prognosisTumor glucose metabolismMass indexPoor outcomeTissue sarcomasCell carcinomaTomography/Clinical prognosisBreast cancerProtective effectObesityCancer
2019
SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia
Nasiri AR, Rodrigues MR, Li Z, Leitner BP, Perry RJ. SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia. Cancer & Metabolism 2019, 7: 10. PMID: 31867105, PMCID: PMC6907191, DOI: 10.1186/s40170-019-0203-1.Peer-Reviewed Original ResearchControlled-release mitochondrial protonophoreInsulin-lowering agentsTumor growthSodium-glucose cotransporter 2 inhibitorsObesity-cancer connectionSustained weight lossCotransporter 2 inhibitorsObesity-associated cancersSubcutaneous insulin infusionInsulin-lowering effectTumor glucose uptakeBreast tumor growthMultiple comparisonsMultiple tumor typesSGLT2 inhibitionSGLT2 inhibitorsObese miceInsulin infusionColon cancer progressionTherapeutic approachesMouse modelBonferroni multiple comparisonsGlucose metabolismColon cancerHyperinsulinemia