2025
Predicting response to neoadjuvant chemotherapy in muscle-invasive bladder cancer via interpretable multimodal deep learning
Bai Z, Osman M, Brendel M, Tangen C, Flaig T, Thompson I, Plets M, Scott Lucia M, Theodorescu D, Gustafson D, Daneshmand S, Meeks J, Choi W, Dinney C, Elemento O, Lerner S, McConkey D, Faltas B, Wang F. Predicting response to neoadjuvant chemotherapy in muscle-invasive bladder cancer via interpretable multimodal deep learning. Npj Digital Medicine 2025, 8: 174. PMID: 40121304, PMCID: PMC11929913, DOI: 10.1038/s41746-025-01560-y.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerResponse to neoadjuvant chemotherapyNeoadjuvant chemotherapyBladder cancerPredicting response to neoadjuvant chemotherapyOptimal treatment strategyImprove patient survivalImproving clinical outcomesGene expression profilesBladder preservationPredictive biomarkersPatient survivalUnnecessary treatmentClinical outcomesTreatment responseRNA sequencingTumor heterogeneityTreatment strategiesClinical trialsGene signatureExpression profilesMolecular determinantsCancerChemotherapyBuilding accurate predictive modelsHeme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis
Nair R, Vu A, Freer A, Bhatia K, Wang D, Savani M, Matulis S, Lonial S, Jaye D, Boise L, Seo S, Corson T, Nooka A, Bhatt S, McBrayer S, Gupta V, Hu X, Barwick B, Reddi A, Shanmugam M. Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis. Blood 2025, 145: 732-747. PMID: 39693611, DOI: 10.1182/blood.2024025690.Peer-Reviewed Original ResearchConceptsElectron transport chainBcl-2Heme biosynthesisBCL-2 antagonismElectron transport chain activityIron-containing prosthetic groupMultiple myelomaB-cell lymphoma 2MEK-ERK signalingGene signatureActivation of prosurvivalApoptotic thresholdPurine biosynthesisPenultimate enzymePyrimidine biosynthesisMetabolic rewiringTransport chainProtein kinaseMultiple Myeloma Research Foundation CoMMpass studyBiosynthesisPurine synthesisGenetic profilePrimary MM cellsProsthetic groupProgression-free survivalMetabolic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.
Saliby R, Labaki C, Jammihal T, Soulati H, Gallegos J, Peris A, McCurry D, Shah V, Poduval D, El Zarif T, El Ahmar N, Nabil Laimon Y, Bagheri Sheshdeh A, Eid M, Krajewski K, Signoretti S, Van Allen E, Shukla S, Choueiri T, Braun D. Metabolic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma. Journal Of Clinical Oncology 2025, 43: 571-571. DOI: 10.1200/jco.2025.43.5_suppl.571.Peer-Reviewed Original ResearchProgression-free survivalImmune checkpoint inhibitorsRenal cell carcinomaComplete responsePartial responseProgressive diseaseWhole-exome sequencingMetabolic gene signatureOverall survivalVEGF inhibitorsCell carcinomaGene set enrichment analysisER patientsSignature scorePatients treated with immune checkpoint inhibitorsResponse to immune checkpoint inhibitionResponse to ICIExceptional responseAdvanced clear cell renal cell carcinomaProgression-free survival predictorsProlonged progression-free survivalMetastatic renal cell carcinomaMultivariate Cox proportional hazards analysisGene signaturePhase III clinical trials
2024
A Lymph Node Immune Score (LNIS) Identifies Prognostic Immune Phenotypes Shared across Head and Neck Cancers
Karpinets T, Garden A, Rosenthal D, Fuller C, Frank S, Gunn G, Phan J, Morrison W, Lee A, Moreno A, Song X, Mitani Y, Ferrarotto R, Gross N, Zhang J, Myers J, El-Naggar A, Spiotto M. A Lymph Node Immune Score (LNIS) Identifies Prognostic Immune Phenotypes Shared across Head and Neck Cancers. International Journal Of Radiation Oncology • Biology • Physics 2024, 120: s222-s223. DOI: 10.1016/j.ijrobp.2024.07.2308.Peer-Reviewed Original ResearchHead and neck squamous cell cancerNon-small cell lung cancerLymph node metastasisPrognostic gene signatureRelapse free survivalExtranodal extensionFree survivalGene signatureImmune microenvironmentImmune scoreLymph nodesImmune phenotypeRejection subtypeHPV-positive HNSCCImmune rejectionAbsence of extranodal extensionNon-small cell lung cancer cohortsHPV-negative HNSCC patientsUnivariate Cox proportional hazards modelHead and neck cancerImmunology-related genesMetastatic lymph nodesLymph node microenvironmentSquamous cell cancerCell lung cancerB cell and aquaporin‐4 antibody relationships with neuromyelitis optica spectrum disorder activity
Bennett J, Pittock S, Paul F, Kim H, Irani S, O'Connor K, Patterson K, Smith M, Gunsior M, Mittereder N, Rees W, Cimbora D, Cree B. B cell and aquaporin‐4 antibody relationships with neuromyelitis optica spectrum disorder activity. Annals Of Clinical And Translational Neurology 2024, 11: 2792-2798. PMID: 39222408, PMCID: PMC11514900, DOI: 10.1002/acn3.52171.Peer-Reviewed Original ResearchNeuromyelitis optica spectrum disorderAquaporin-4B cellsAquaporin-4 immunoglobulin GCirculating B cell subsetsAQP4-IgG titerN-MOmentum studyB-cell countsB cell subsetsBaseline to timePost hoc analysisInebilizumab treatmentAQP4-IgGCD20<sup>+</sup>Subset countsGene signatureHoc analysisInebilizumabNo differenceImmunoglobulin GNeuromyelitisBaselineDisordered activityTitersSpectrum disorderSpatially Informed Gene Signatures for Response to Immunotherapy in Melanoma.
Aung T, Warrell J, Martinez-Morilla S, Gavrielatou N, Vathiotis I, Yaghoobi V, Kluger H, Gerstein M, Rimm D. Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma. Clinical Cancer Research 2024, 30: 3520-3532. PMID: 38837895, PMCID: PMC11326985, DOI: 10.1158/1078-0432.ccr-23-3932.Peer-Reviewed Original ResearchGene signatureResistance to immunotherapyResponse to immunotherapyPrediction of treatment outcomeResistant to treatmentAccurate prediction of treatment outcomePredictive of responseImmunotherapy outcomesMelanoma patientsMelanoma specimensValidation cohortPatient stratificationDiscovery cohortTreatment outcomesImmunotherapyMelanomaTumorPatientsCohortS100BOutcomesGene expression dataGenesCD68+macrophagesExpression dataA Monocyte-specific Gene-signature Predicts Outcomes in Patients With Idiopathic Pulmonary Fibrosis and Is Reproducible in Peripheral Blood, Bronchoalveolar Lavage, and Lung Tissue
Karampitsakos T, Tourki B, Juan-Guardela B, Perrot C, Marlin K, Arsenault A, Binder H, Wuyts W, Rottoli P, Prasse A, Tzouvelekis A, Restrepo Jaramillo R, Qureshi M, Patel K, Bandyopadhyay D, Kaminski N, Herazo-Maya J. A Monocyte-specific Gene-signature Predicts Outcomes in Patients With Idiopathic Pulmonary Fibrosis and Is Reproducible in Peripheral Blood, Bronchoalveolar Lavage, and Lung Tissue. 2024, a2860-a2860. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2860.Peer-Reviewed Original ResearchModeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets
Patil A, Schug J, Liu C, Lahori D, Descamps H, Consortium T, Naji A, Kaestner K, Faryabi R, Vahedi G. Modeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets. Cell Reports Medicine 2024, 5: 101535. PMID: 38677282, PMCID: PMC11148720, DOI: 10.1016/j.xcrm.2024.101535.Peer-Reviewed Original ResearchSingle-cell transcriptomic measurementsGene expression of single cellsGene signatureSingle-cell analysisTranscriptional outputTranscriptomic measurementsUnique gene signatureNon-diabetic organ donorsAnalysis of isletsGene expressionAutoantibody-positive donorsPrediction of T1DHuman isletsBeta cellsCell typesT1D developmentSingle cellsGenesType 1 diabetes progressionCellsT1D onsetType 1 diabetesIsletsImmune cellsNon-diabeticsThe IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer
Amara C, Kami Reddy K, Yuntao Y, Chan Y, Piyarathna D, Dobrolecki L, Shih D, Shi Z, Xu J, Huang S, Ellis M, Apolo A, Ballester L, Gao J, Hansel D, Lotan Y, Hodges H, Lerner S, Creighton C, Sreekumar A, Zheng W, Msaouel P, Kavuri S, Putluri N. The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer. Nature Communications 2024, 15: 1373. PMID: 38355560, PMCID: PMC10867091, DOI: 10.1038/s41467-024-45132-2.Peer-Reviewed Original ResearchConceptsSignaling axisSMARCB1-deficient tumorsSMARCB1 deficiencyBladder cancerChromatin accessibilitySTAT3 inhibitorTumor growthSMARCB1 lossPatient-derived xenograft modelsCell line-derived xenograftsTherapeutic vulnerabilitiesTarget pathwaysReduced tumor growthIncreased tumor growthCell linesIn vivo modelsSTAT3Gene signatureSMARCB1TTI-101Solid tumorsXenograft modelClinical evaluationDisease progressionTumorMultiomics profiling of urothelial carcinoma in situ reveals CIS-specific gene signature and immune characteristics
Anurag M, Strandgaard T, Kim S, Dou Y, Comperat E, Al-Ahmadie H, Inman B, Taber A, Nordentoft I, Jensen J, Dyrskjøt L, Lerner S. Multiomics profiling of urothelial carcinoma in situ reveals CIS-specific gene signature and immune characteristics. IScience 2024, 27: 109179. PMID: 38439961, PMCID: PMC10910238, DOI: 10.1016/j.isci.2024.109179.Peer-Reviewed Original ResearchCarcinoma in situCarcinoma in situ lesionsUrothelial carcinoma in situPapillary tumorsAggressive phenotypeAssociated with carcinoma in situNon-muscle-invasive bladder cancerCarcinoma in situ samplesPD-1-positive cellsImmune marker expressionBladder cancerImmunological landscapeMarker expressionTumorGene signatureMutational heterogeneityImmune characteristicsMutated genesExpression signaturesTargeting mTORHigher expressionTime pointsMutation analysisMultiomic profilingLesions
2023
Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease
Young J, Park H, Kim M, Par-Young J, Bartlett H, Kim H, Unlu S, Osmani L, Shin M, Bucala R, van Dyck C, Allore H, Mecca A, You S, Kang I. Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease. Immunity & Ageing 2023, 20: 71. PMID: 38042785, PMCID: PMC10693128, DOI: 10.1186/s12979-023-00396-y.Peer-Reviewed Original ResearchPeripheral bloodT cellsAlzheimer's diseaseEM CD8Memory CD8Gene signatureAge-related immune changesIL-7 receptor alphaEffector memory CD8Strong risk factorT cell expansionAD genesAge-associated expansionImmune changesRisk factorsCD8Dementia patientsIL-7RNeuropsychological testingReceptor alphaNeurocognitive functionRT-qPCR resultsDisease severityPatientsNormal personsInflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma
Dolgalev I, Zhou H, Murrell N, Le H, Sakellaropoulos T, Coudray N, Zhu K, Vasudevaraja V, Yeaton A, Goparaju C, Li Y, Sulaiman I, Tsay J, Meyn P, Mohamed H, Sydney I, Shiomi T, Ramaswami S, Narula N, Kulicke R, Davis F, Stransky N, Smolen G, Cheng W, Cai J, Punekar S, Velcheti V, Sterman D, Poirier J, Neel B, Wong K, Chiriboga L, Heguy A, Papagiannakopoulos T, Nadorp B, Snuderl M, Segal L, Moreira A, Pass H, Tsirigos A. Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma. Nature Communications 2023, 14: 6764. PMID: 37938580, PMCID: PMC10632519, DOI: 10.1038/s41467-023-42327-x.Peer-Reviewed Original ResearchConceptsTumor-adjacent tissuesDisease progressionInflammatory signatureEarly-stage lung adenocarcinoma patientsSuccessful surgical resectionLong-term patientsInflammatory gene signatureLung adenocarcinoma patientsStrongest clinical predictorsNon-immune cellsNormal lung tissuesAdjacent normal tissuesCancer Genome AtlasSurgical resectionClinical predictorsClinical outcomesAdenocarcinoma patientsPredictive biomarkersWorse outcomesLung tissueDisease outcomeLung adenocarcinomaHigh riskSingle-cell transcriptomic analysisGene signatureSpliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia
Croucher P, Ridinger M, Becker P, Lin T, Silberman S, Wang E, Zeidan A. Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia. Annals Of Hematology 2023, 102: 3049-3059. PMID: 37702821, PMCID: PMC10567832, DOI: 10.1007/s00277-023-05442-9.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AML patientsAML patientsMyeloid leukemiaRefractory (R/R) AMLRelapsed/refractory (R/R) AMLHigher CR/CRi ratesCR/CRi rateRefractory acute myeloid leukemiaGene signaturePhase 1b/2 studyPhase 1b/2 trialPhase 1b trialBone marrow blastsSF mutationsBone marrow samplesCRi rateComplete remissionMarrow blastsClinical responseCount recoveryInitial safetyMarrow samplesPotential therapyMolecular predictorsA membrane-associated MHC-I inhibitory axis for cancer immune evasion
Chen X, Lu Q, Zhou H, Liu J, Nadorp B, Lasry A, Sun Z, Lai B, Rona G, Zhang J, Cammer M, Wang K, Al-Santli W, Ciantra Z, Guo Q, You J, Sengupta D, Boukhris A, Zhang H, Liu C, Cresswell P, Dahia P, Pagano M, Aifantis I, Wang J. A membrane-associated MHC-I inhibitory axis for cancer immune evasion. Cell 2023, 186: 3903-3920.e21. PMID: 37557169, PMCID: PMC10961051, DOI: 10.1016/j.cell.2023.07.016.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSolid cancersImmune evasionCancer immune evasionImmune checkpoint blockadeMultiple solid cancersMajor Histocompatibility Complex Class I Antigen PresentationPotential therapeutic targetCell-dependent mannerCell immunityCancer survivalMyeloid leukemiaAntigen presentationTherapeutic targetTransmembrane protein 127Tumor growthGene signatureCancer treatmentCancerPeptide-MHCMHCLeukemiaSushi domainTrimolecular complexE3 ubiquitin ligase WWP2A membrane-associated inhibitory axis of MHC-I presentation for cancer immune evasion
Lu Q, Chen X, Zhou H, Liu J, Nadorp B, Lasry A, Sun Z, Zhang J, Cammer M, Wang K, Ciantra Z, You J, Guo Q, Zhang H, Sengupta D, Boukhris A, Liu C, Cresswell P, Dahia P, Aifantis I, Wang J. A membrane-associated inhibitory axis of MHC-I presentation for cancer immune evasion. The Journal Of Immunology 2023, 210: 89.12-89.12. DOI: 10.4049/jimmunol.210.supp.89.12.Peer-Reviewed Original ResearchAcute myeloid leukemiaInhibitory axisSolid cancersImmune evasionT cell-dependent mannerCancer immune evasionImmune checkpoint blockadeT cell immunityNumber of tumorsMultiple solid cancersCell-dependent mannerApplicable therapeutic targetMDS FoundationCancer survivalMyeloid leukemiaTherapeutic targetTransmembrane protein 127Tumor growthGene signatureCancer treatmentMHCPeptide-MHCLeukemiaSushi domainCancerRegulatory T cells in peripheral tissue tolerance and diseases
Cheru N, Hafler D, Sumida T. Regulatory T cells in peripheral tissue tolerance and diseases. Frontiers In Immunology 2023, 14: 1154575. PMID: 37197653, PMCID: PMC10183596, DOI: 10.3389/fimmu.2023.1154575.Peer-Reviewed Original ResearchConceptsTissue-resident TregsRegulatory T cellsT cellsResident TregsTissue TregsAutoimmune diseasesCommon human autoimmune diseasesAutoreactive T cellsHuman autoimmune diseasesNon-immune cellsNon-lymphoid tissuesTissue-resident cellsTreg poolTreg studiesEffector cytokinesPeripheral toleranceTreg functionIPEX syndromeImmune homeostasisSpecific tissue environmentsTregsSuppressive functionLoss of functionResident cellsGene signatureLeveraging GWAS data derived from a large cooperative group trial to assess the risk of taxane-induced peripheral neuropathy (TIPN) in patients being treated for breast cancer: Part 2—functional implications of a SNP cluster associated with TIPN risk in patients being treated for breast cancer
Lustberg M, Wu X, Fernández-Martínez J, de Andrés-Galiana E, Philips S, Leibowitz J, Schneider B, Sonis S. Leveraging GWAS data derived from a large cooperative group trial to assess the risk of taxane-induced peripheral neuropathy (TIPN) in patients being treated for breast cancer: Part 2—functional implications of a SNP cluster associated with TIPN risk in patients being treated for breast cancer. Supportive Care In Cancer 2023, 31: 178. PMID: 36809570, PMCID: PMC11344472, DOI: 10.1007/s00520-023-07617-6.Peer-Reviewed Original ResearchConceptsGWAS dataSNP clustersFunctional analysisGO termsNon-protein coding genesGene Ontology termsGene Set Enrichment AnalysisCluster of SNPsNervous system developmentCoding genesRetinoic acid bindingOntology termsProtein kinase C bindingEnrichment analysisMetabolic processesGenesAcid bindingGlycosyltransferase activitySNPsPathological implicationsGWASC bindingGene signaturePhenotypeTransferase activityCXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis
Dunbar A, Kim D, Lu M, Farina M, Bowman R, Yang J, Park Y, Karzai A, Xiao W, Zaroogian Z, O’Connor K, Mowla S, Gobbo F, Verachi P, Martelli F, Sarli G, Xia L, Elmansy N, Kleppe M, Chen Z, Xiao Y, McGovern E, Snyder J, Krishnan A, Hill C, Cordner K, Zouak A, Salama M, Yohai J, Tucker E, Chen J, Zhou J, McConnell T, Migliaccio A, Koche R, Rampal R, Fan R, Levine R, Hoffman R. CXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis. Blood 2023, 141: 2508-2519. PMID: 36800567, PMCID: PMC10273167, DOI: 10.1182/blood.2022015418.Peer-Reviewed Original ResearchConceptsConstitutive JAK/STATHematopoietic stem/progenitor cellsJAK/STATBone marrow fibrosisStem/progenitor cellsMPN cellsMarrow fibrosisHuman cancersMyeloproliferative neoplasmsPrimary cellsProgenitor cellsMechanistic insightsPharmacologic inhibitionGenetic deletionSignaling contributesGene signatureJAK inhibitor therapyTherapeutic targetingEnhanced proliferationCritical roleTherapeutic targetCXCL8/MF developmentMF pathogenesisInhibitor therapyMicroRNA–mRNA networks are dysregulated in opioid use disorder postmortem brain: Further evidence for opioid-induced neurovascular alterations
Grimm S, Mendez E, Stertz L, Meyer T, Fries G, Gandhi T, Kanchi R, Selvaraj S, Teixeira A, Kosten T, Gunaratne P, Coarfa C, Walss-Bass C. MicroRNA–mRNA networks are dysregulated in opioid use disorder postmortem brain: Further evidence for opioid-induced neurovascular alterations. Frontiers In Psychiatry 2023, 13: 1025346. PMID: 36713930, PMCID: PMC9878702, DOI: 10.3389/fpsyt.2022.1025346.Peer-Reviewed Original ResearchOpioid use disorderUse disorderPostmortem brainsDorsolateral prefrontal cortexResponses to opioid drugsGenotype-Tissue ExpressionImmune system alterationsPrefrontal cortexNeurobiological alterationsBlood-brain barrierMiRNA targetsEpigenetic regulation of gene functionOpioid drugsRegulation of gene functionOpioid abuseTGF-betaGene signatureInflammatory pathwaysPotential functional impactSystem alterationsImmune systemBrain transcriptomeEndothelial cellsNeurovascular alterationsPostmortem samples
2022
Implication of IL-7 receptor alpha chain expression by CD8+ T cells and its signature in defining biomarkers in aging
Shin M, Park H, Young J, Kang I. Implication of IL-7 receptor alpha chain expression by CD8+ T cells and its signature in defining biomarkers in aging. Immunity & Ageing 2022, 19: 66. PMID: 36544153, PMCID: PMC9768896, DOI: 10.1186/s12979-022-00324-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsT cellsImmune agingHost defenseIL-7 receptor alpha chainFrequencies of naïveT cell subsetsAlpha chain expressionAssociation of CD8Age-associated conditionsReceptor alpha chainMemory CD8Treatment of illnessCell subsetsInflammatory disordersIL-7RαCD8High riskImmune functionTherapeutic interventionsImmune systemPotential biomarkersGene signatureChain expressionOlder adultsBiomarkers
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