Julie F. Cheung
Postdoctoral AssociateAbout
Research
Publications
2023
A PERK-Specific Inhibitor Blocks Metastatic Progression by Limiting Integrated Stress Response-Dependent Survival of Quiescent Cancer Cells.
Calvo V, Zheng W, Adam-Artigues A, Staschke K, Huang X, Cheung J, Nobre A, Fujisawa S, Liu D, Fumagalli M, Surguladze D, Stokes M, Nowacek A, Mulvihill M, Farias E, Aguirre-Ghiso J. A PERK-Specific Inhibitor Blocks Metastatic Progression by Limiting Integrated Stress Response-Dependent Survival of Quiescent Cancer Cells. Clinical Cancer Research 2023, 29: 5155-5172. PMID: 37982738, PMCID: PMC10842363, DOI: 10.1158/1078-0432.ccr-23-1427.Peer-Reviewed Original ResearchCancer cellsIntegrated stress responsePERK inhibitionRounds of therapyPERK inhibitorDormant cancer cellsQuiescent cancer cellsMicro-metastatic lesionsAnti-proliferative therapiesMetastasis biopsiesMetastatic burdenCDK4/6 inhibitorsPDX modelsSingle-cell gene expression profilingHER2 activityMetastatic progressionGene expression profilingSurvival factorUnresolved ER stressHigh expressionMouse syngeneicER stressMetastasisHER2Therapy1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. 1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma. 2023, a1133-a1133. DOI: 10.1136/jitc-2023-sitc2023.1025.Peer-Reviewed Original ResearchIL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive mice5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling
Singh D, Carcamo S, Farias E, Hasson D, Zheng W, Sun D, Huang X, Cheung J, Nobre A, Kale N, Sosa M, Bernstein E, Aguirre-Ghiso J. 5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling. Cell Reports 2023, 42: 112560. PMID: 37267946, PMCID: PMC10592471, DOI: 10.1016/j.celrep.2023.112560.Peer-Reviewed Original ResearchConceptsDisseminated cancer cellsCancer cellsDNA methylation inhibitorNon-proliferative stateAnti-proliferative functionTranscriptional reprogrammingChromatin remodelingRetinoic acid receptorsTranscriptional programsMethylation inhibitorGrowth factor βMicroenvironmental signalsSMAD4 knockdownBreast cancer cellsDormancySuppress metastasisRARα-specific agonistLung metastasis formationNeck squamous cell carcinomaReprogrammingRetinoic acidSquamous cell carcinomaTrans retinoic acidFactor βMetastasis formation
2021
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Cui C, Wang J, Fagerberg E, Chen PM, Connolly KA, Damo M, Cheung JF, Mao T, Askari AS, Chen S, Fitzgerald B, Foster GG, Eisenbarth SC, Zhao H, Craft J, Joshi NS. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. Cell 2021, 184: 6101-6118.e13. PMID: 34852236, PMCID: PMC8671355, DOI: 10.1016/j.cell.2021.11.007.Peer-Reviewed Original ResearchConceptsCD8 TB cellsTfh cellsLung adenocarcinomaTfh-B cell interactionsTumor-specific B cellsFollicular helper cellsAnti-tumor immunityB cell signaturesCell effector functionsGerminal center formationGC B cellsCD4 THelper cellsTumor controlTumor neoantigensEffector functionsCell collaborationCell responsesCell signatureTumor cellsSignature correlatesNeoantigensCell functionCD4A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma
Fitzgerald B, Connolly KA, Cui C, Fagerberg E, Mariuzza DL, Hornick NI, Foster GG, William I, Cheung JF, Joshi NS. A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma. Cell Reports Methods 2021, 1: 100080. PMID: 34632444, PMCID: PMC8500377, DOI: 10.1016/j.crmeth.2021.100080.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaNeoantigen expressionTumor-specific CD8 T cellsCD8 T cellsImmune checkpoint therapyInfection-induced inflammationExpression of neoantigensCommon lung cancerLUAD cell linesCheckpoint therapyLung cancerTherapeutic responseT cellsImmune responseMouse modelCell responsesTumor inductionTumorsAdenocarcinomaCell linesNeoantigensKrasFuture studiesExpressionImmunotherapyA reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response
Connolly KA, Kuchroo M, Venkat A, Khatun A, Wang J, William I, Hornick NI, Fitzgerald BL, Damo M, Kasmani MY, Cui C, Fagerberg E, Monroy I, Hutchins A, Cheung JF, Foster GG, Mariuzza DL, Nader M, Zhao H, Cui W, Krishnaswamy S, Joshi NS. A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response. Science Immunology 2021, 6: eabg7836. PMID: 34597124, PMCID: PMC8593910, DOI: 10.1126/sciimmunol.abg7836.Peer-Reviewed Original ResearchConceptsTumor-specific CD8T cellsTumor microenvironmentOngoing anti-tumor immune responseChronic lymphocytic choriomeningitis virus (LCMV) infectionTumor-draining lymph nodesAnti-tumor immune responseLymphocytic choriomeningitis virus infectionIntratumoral T cellsEfficacy of immunotherapyT cell responsesTumor-draining lymphAntitumor T cellsT cell terminal differentiationStem-like CD8Immunologic shiftGene expression signaturesLymph nodesTerminal differentiationLung tumorsVirus infectionLung adenocarcinomaImmune responseCD8Cell responsesPriming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis
Luu T, Cheung JF, Baccon J, Waldner H. Priming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis. PLOS ONE 2021, 16: e0250340. PMID: 33891644, PMCID: PMC8064509, DOI: 10.1371/journal.pone.0250340.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisT cell responsesDendritic cellsT cellsMultiple sclerosisCell responsesAutoimmune encephalomyelitisSJL miceProteolipid proteinPro-inflammatory T cell responsesAbsence of DCsImportance of DCsPLP-specific T cellsSpontaneous experimental autoimmune encephalomyelitisMyelin-specific T cellsSelf-reactive T cellsSevere experimental autoimmune encephalomyelitisDendritic cells resultsSelf-reactive CD4Myelin antigensCNS antigensInflammatory CD4Autoimmune diseasesDC deficiencyAnimal modelsBone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2
Nobre A, Risson E, Singh D, Di Martino J, Cheung J, Wang J, Johnson J, Russnes H, Bravo-Cordero J, Birbrair A, Naume B, Azhar M, Frenette P, Aguirre-Ghiso J. Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2. Nature Cancer 2021, 2: 327-339. PMID: 34993493, PMCID: PMC8730384, DOI: 10.1038/s43018-021-00179-8.Peer-Reviewed Original ResearchConceptsMesenchymal stem cellsDTC dormancyHematopoietic stem cell quiescenceStem cellsStem cell quiescenceBone morphogenetic proteinTGF-β2Niche homeostasisMorphogenetic proteinsCell quiescenceBone marrow microenvironmentGenetic depletionP27 inductionDormancyConditional knockoutMarrow microenvironmentMetastatic outgrowthEstrogen receptor-positive BCExtrinsic factorsGrowth factorCellsTumor cellsBone relapseSystemic recurrenceBreast cancer
2020
Inducible de novo expression of neoantigens in tumor cells and mice
Damo M, Fitzgerald B, Lu Y, Nader M, William I, Cheung JF, Connolly KA, Foster GG, Akama-Garren E, Lee DY, Chang GP, Gocheva V, Schmidt LM, Boileve A, Wilson JH, Cui C, Monroy I, Gokare P, Cabeceiras P, Jacks T, Joshi NS. Inducible de novo expression of neoantigens in tumor cells and mice. Nature Biotechnology 2020, 39: 64-73. PMID: 32719479, PMCID: PMC7854852, DOI: 10.1038/s41587-020-0613-1.Peer-Reviewed Original ResearchConceptsT cell responsesLevel of regulationRNA splicingDNA recombinationGenetic regulationTolerance mechanismsInducible expressionNeoantigen expressionCell responsesNaïve T-cell responsesCD4 T cell responsesTumor cell linesPeripheral tolerance mechanismsT cell toleranceCentral T cell toleranceCell linesExpressionNovo expressionTight controlEndogenous CD8Antitumor immunityPeripheral toleranceAutoimmune diseasesT cellsThymus results