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 expressionGene 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 rate
2022
Isotope 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 linesInsulin 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
The 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