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
2025
Evaluation of nonspecific reactivity rates across three immunohematology testing platforms with assessment of subsequent specific alloantibody development
Yurtsever N, Carmichael G, Malonis R, Madden M, Isik N, Ahmed M, Bizzario L, Shah B, Tormey C, Lee E. Evaluation of nonspecific reactivity rates across three immunohematology testing platforms with assessment of subsequent specific alloantibody development. Transfusion 2025, 65: 978-984. PMID: 40251842, PMCID: PMC12092180, DOI: 10.1111/trf.18256.Peer-Reviewed Original ResearchNonspecific reactivityAntibody screeningStrength of reactivityRate of positivityReagent red cellsAlloantibody developmentKruskal-Wallis testAntibody historyChart reviewPretransfusion testingAntibody identificationIRB approvalIdentification panelKruskal-WallisPositive screenAntibody detectionRed cellsAntibodiesAlloantibodiesStudy periodReactivation rateTube testNonspecific reactionsScreeningCellsMitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism
Steiner K, Young A, Patterson A, Sugiura A, Watson M, Preston S, Zhelonkin A, Jennings E, Chi C, Heintzman D, Pahnke A, Toudji Y, Hatem Z, Madden M, Arner E, Sewell A, Blount A, Okparaugo R, Fallman E, Krystofiak E, Sheldon R, Gibson-Corley K, Voss K, Nowinski S, Jones R, Mogilenko D, Rathmell J. Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism. The Journal Of Immunology 2025, 214: 958-976. PMID: 40204636, PMCID: PMC12123211, DOI: 10.1093/jimmun/vkaf034.Peer-Reviewed Original ResearchConceptsT cell subsetsCD4+ T cell subsetsMitochondrial fatty acid synthesisT cell functionT cellsFatty acid synthesisDecreased mitochondrial respirationTricarboxylic acid intermediatesLipid metabolism genesT cell fateSensitivity to ferroptosisIncreased cell deathCD4+ T cell functionCD8+ T cell numbersCD4+ T cell proliferationMitochondrial stressMetabolic genesCD4+ T cellsCRISPR/Cas9 screenMitochondrial respirationModel of inflammatory bowel diseaseAcid synthesisFitness disadvantageMemory T cellsT cell numbersCorrection: EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair
Koyen A, Madden M, Park D, Minten E, Kapoor-Vazirani P, Werner E, Pfister N, Haji-Seyed-Javadi R, Zhang H, Xu J, Deng N, Duong D, Pecen T, Frazier Z, Nagel Z, Lazaro J, Mouw K, Seyfried N, Moreno C, Owonikoko T, Deng X, Yu D. Correction: EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair. Oncogene 2025, 44: 928-930. PMID: 40097809, DOI: 10.1038/s41388-025-03345-9.Peer-Reviewed Original Research
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