Matthew Z Madden, MD, PhD
he/him/his
Hospital ResidentCards
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Research
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Featured Publications
Differential Effects of Glutamine Inhibition Strategies on Antitumor CD8 T Cells.
Madden M, Ye X, Chi C, Fisher E, Wolf M, Needle G, Bader J, Patterson A, Reinfeld B, Landis M, Hathaway E, Muka J, O'Neil R, Karijolich J, Philip M, Rathmell J. Differential Effects of Glutamine Inhibition Strategies on Antitumor CD8 T Cells. The Journal Of Immunology 2023, 211: 563-575. PMID: 37341499, PMCID: PMC10526752, DOI: 10.4049/jimmunol.2200715.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsActivated T cellsAntitumor CD8 T cellsCD8 T cell differentiationAdoptive transfer studiesMurine CD8 T cellsQ treatmentAdoptive cell therapyT cell functionT cell dependenceT cell differentiationT cell activationCB-839 treatmentAutoimmune diseasesFunctional outcomeTumor infiltrationTreatment strategiesGlucose metabolismCell activationTumor growthCB-839Cell therapyCell functionOxidative metabolismThe Complex Integration of T-cell Metabolism and Immunotherapy
Madden M, Rathmell J. The Complex Integration of T-cell Metabolism and Immunotherapy. Cancer Discovery 2021, 11: 1636-1643. PMID: 33795235, PMCID: PMC8295173, DOI: 10.1158/2159-8290.cd-20-0569.Peer-Reviewed Original ResearchConceptsT cell metabolismT cell functionT cellsImmune-oncology approachesEffector T cellsOxidative metabolismAdoptive cell therapyT cell interactionsT cell fateAntitumor immunityCancer immunotherapyImmune oncologyTumor microenvironmentNormal stimulationCell therapyTumorsAerobic glycolysisMetabolic reprogrammingMetabolic reprogramming eventsImmunotherapyMetabolismCellsTherapyCancerCentral roleCell-programmed nutrient partitioning in the tumour microenvironment
Reinfeld B, Madden M, Wolf M, Chytil A, Bader J, Patterson A, Sugiura A, Cohen A, Ali A, Do B, Muir A, Lewis C, Hongo R, Young K, Brown R, Todd V, Huffstater T, Abraham A, O’Neil R, Wilson M, Xin F, Tantawy M, Merryman W, Johnson R, Williams C, Mason E, Mason F, Beckermann K, Vander Heiden M, Manning H, Rathmell J, Rathmell W. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature 2021, 593: 282-288. PMID: 33828302, PMCID: PMC8122068, DOI: 10.1038/s41586-021-03442-1.Peer-Reviewed Original ResearchConceptsPositron emission tomographyTumor microenvironmentCancer cellsImmune cellsCell-intrinsic programsTumor-infiltrating immune cellsGlucose uptakeBasis of tumorImmune cell metabolismCell-intrinsic mannerSpecific cell subsetsEnhanced glucose uptakeCell subsetsMetabolism of glucoseT cellsImmune evasionUptake of glucoseCancer modelMyeloid cellsEmission tomographyPET tracersSpecific cell populationsCell populationsHigh uptakeGlutamine metabolism
2024
Androgen signaling restricts glutaminolysis to drive sex-specific Th17 metabolism in allergic airway inflammation
Chowdhury N, Cephus J, Pilier E, Wolf M, Madden M, Kuehnle S, McKernan K, Jennings E, Arner E, Heintzman D, Chi C, Sugiura A, Stier M, Voss K, Ye X, Scales K, Krystofiak E, Gandhi V, Guzy R, Cahill K, Sperling A, Peebles R, Rathmell J, Newcomb D. Androgen signaling restricts glutaminolysis to drive sex-specific Th17 metabolism in allergic airway inflammation. Journal Of Clinical Investigation 2024, 134: e177242. PMID: 39404231, PMCID: PMC11601904, DOI: 10.1172/jci177242.Peer-Reviewed Original ResearchTh17 cellsAirway inflammationAR signalingT cellsAndrogen receptorTh17-mediated airway inflammationAirway inflammation mouse modelCD4+ T cellsExpression of glutamine transportersCirculating T cellsRegulation of Th17 cellsAllergic airway inflammationCell-mediated diseasesGlutamine uptakeInflammation mouse modelAndrogen signalingMouse modelTh17Increased prevalenceReduced expressionInflammationAndrogenGlutamine transportGlutaminolysisDecreased glutaminolysisAuthor Correction: Obesity induces PD-1 on macrophages to suppress anti-tumour immunity
Bader J, Wolf M, Lupica-Tondo G, Madden M, Reinfeld B, Arner E, Hathaway E, Steiner K, Needle G, Hatem Z, Landis M, Faneuff E, Blackman A, Wolf E, Cottam M, Ye X, Bates M, Smart K, Wang W, Pinheiro L, Christofides A, Smith D, Boussiotis V, Haake S, Beckermann K, Wellen K, Reinhart-King C, Serezani C, Lee C, Aubrey C, Chen H, Rathmell W, Hasty A, Rathmell J. Author Correction: Obesity induces PD-1 on macrophages to suppress anti-tumour immunity. Nature 2024, 631: e16-e16. PMID: 38982216, DOI: 10.1038/s41586-024-07794-2.Peer-Reviewed Original ResearchObesity induces PD-1 on macrophages to suppress anti-tumour immunity
Bader J, Wolf M, Lupica-Tondo G, Madden M, Reinfeld B, Arner E, Hathaway E, Steiner K, Needle G, Hatem Z, Landis M, Faneuff E, Blackman A, Wolf E, Cottam M, Ye X, Bates M, Smart K, Wang W, Pinheiro L, Christofides A, Smith D, Boussiotis V, Haake S, Beckermann K, Wellen K, Reinhart-King C, Serezani C, Lee C, Aubrey C, Chen H, Rathmell W, Hasty A, Rathmell J. Obesity induces PD-1 on macrophages to suppress anti-tumour immunity. Nature 2024, 630: 968-975. PMID: 38867043, PMCID: PMC11456854, DOI: 10.1038/s41586-024-07529-3.Peer-Reviewed Original ResearchTumor-associated macrophagesPD-1 expressionInduced PD-1 expressionPD-1T cellsIncreased CD8+ T cell activationCD8+ T cell activationResponse to immune checkpoint blockade therapyT-cell stimulatory potentialTumor-associated macrophage expressionSuppress anti-tumor immunityImmune checkpoint blockade therapyObesity-cancer connectionPD-1 deficiencyAnti-PD-1PD-1 blockadePD-1 inhibitionAnti-tumor immunityCheckpoint blockade therapyTargeting PD-1Tumor immune surveillancePD-1 immunotherapyAntigen presentation capabilityMarkers of exhaustionExpression of CD86VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis
Wolf M, Madden M, Arner E, Bader J, Ye X, Vlach L, Tigue M, Landis M, Jonker P, Hatem Z, Steiner K, Gaines D, Reinfeld B, Hathaway E, Xin F, Tantawy M, Haake S, Jonasch E, Muir A, Weiss V, Beckermann K, Rathmell W, Rathmell J. VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis. Journal Of Clinical Investigation 2024, 134: e173934. PMID: 38618956, PMCID: PMC11014672, DOI: 10.1172/jci173934.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaTumor-associated macrophagesVon Hippel-LindauImmune landscapeTumor microenvironmentVon Hippel-Lindau lossVHL-KOImmune cellsAnti-programmed cell death 1VHL lossInflammatory transcriptional signaturesTumor immune landscapeCell death 1Cell renal cell carcinomaRenal cell carcinomaHuman ccRCC tumorsTreatment of clear cell renal cell carcinomaMyeloid microenvironmentDeath-1RENCA modelCell carcinomaCcRCC tumorsLymphoid cellsChemokine CX3CL1Renal tumorigenesis
2023
STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy
Wang-Bishop L, Kimmel B, Ngwa V, Madden M, Baljon J, Florian D, Hanna A, Pastora L, Sheehy T, Kwiatkowski A, Wehbe M, Wen X, Becker K, Garland K, Schulman J, Shae D, Edwards D, Wolf M, Delapp R, Christov P, Beckermann K, Balko J, Rathmell W, Rathmell J, Chen J, Wilson J. STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy. Science Immunology 2023, 8: eadd1153. PMID: 37146128, PMCID: PMC10226150, DOI: 10.1126/sciimmunol.add1153.Peer-Reviewed Original ResearchConceptsSTING-activating nanoparticlesT cell infiltrationCell infiltrationT cellsAdoptive T-cell therapyMultiple mouse tumor modelsT-cell adhesion moleculesImmune checkpoint inhibitorsEffector T cellsAntitumor T cellsT-cell therapyEffective tumor controlCyclic dinucleotide STING agonistsEndothelial cell expressionTumor-associated vasculatureMouse tumor modelsCheckpoint inhibitorsCancer immunotherapyTumor controlVascular normalizationIntravenous administrationCell adhesion moleculeAntitumor functionSTING agonistsCell expression
2022
Acly Deficiency Enhances Myelopoiesis through Acetyl Coenzyme A and Metabolic–Epigenetic Cross-Talk
Greenwood D, Ramsey H, Nguyen P, Patterson A, Voss K, Bader J, Sugiura A, Bacigalupa Z, Schaefer S, Ye X, Dahunsi D, Madden M, Wellen K, Savona M, Ferrell P, Rathmell J. Acly Deficiency Enhances Myelopoiesis through Acetyl Coenzyme A and Metabolic–Epigenetic Cross-Talk. ImmunoHorizons 2022, 6: 837-850. PMID: 36547387, PMCID: PMC9935084, DOI: 10.4049/immunohorizons.2200086.Peer-Reviewed Original ResearchConceptsChromatin accessibilityMyeloid differentiationTransposase-accessible chromatin sequencingEpigenetic cross talkHematopoietic stemSingle-cell RNA sequencingFamily transcription factorsProgenitor cellsSmall molecule inhibitionSingle-cell assaysATP-citrate lyaseEpigenetic marksAcetyl coenzyme AGene expression signaturesEpigenetic modificationsTranscription factorsRNA sequencingACLY inhibitionMitochondrial metabolismReactive oxygen speciesMitochondrial polarizationMurine hematopoiesisCell metabolismMus musculusEssential substrateStimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer
Glass E, Hoover A, Bullock K, Madden M, Reinfeld B, Harris W, Parker D, Hufnagel D, Crispens M, Khabele D, Rathmell W, Rathmell J, Wilson A, Giorgio T, Yull F. Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer. BMC Cancer 2022, 22: 497. PMID: 35513776, PMCID: PMC9074180, DOI: 10.1186/s12885-022-09612-2.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesAnti-tumor immunityOvarian cancerConsecutive days' treatmentTumor burdenMouse modelSolid tumorsImmunosuppressive tumor-associated macrophagesAnti-tumor phenotypeLate-stage diseaseClear therapeutic effectImmune cell compositionImmunosuppressive tumor microenvironmentM1 macrophage polarizationStrong translational potentialOvarian cancer modelFuture clinical studiesNF-κB alphaOvarian cancer progressionHigh response rateNF-κB activityEvidence of toxicityNuclear factor-kappaBInducible transgenic miceID8 model