2022
Transformer-based protein generation with regularized latent space optimization
Castro E, Godavarthi A, Rubinfien J, Givechian K, Bhaskar D, Krishnaswamy S. Transformer-based protein generation with regularized latent space optimization. Nature Machine Intelligence 2022, 4: 840-851. DOI: 10.1038/s42256-022-00532-1.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
Glycolytic expression in lower-grade glioma reveals an epigenetic association between IDH mutation status and PDL1/2 expression
Givechian K, Garner C, Benz S, Rabizadeh S, Soon-Shiong P. Glycolytic expression in lower-grade glioma reveals an epigenetic association between IDH mutation status and PDL1/2 expression. Neuro-Oncology Advances 2020, 3: vdaa162. PMID: 33532725, PMCID: PMC7837356, DOI: 10.1093/noajnl/vdaa162.Peer-Reviewed Original ResearchChIP-seq dataEpigenetic linkR132H/Promoter methylationPromoter methylation patternsPromoter H3K4me3Cancer Genome AtlasGenomic analysisDNA methylationRNA-seqImmortalized human astrocytesMethylation patternsMethylation dataEpigenetic associationsCheckpoint genesCell line dataMethylation levelsMethylationWild-type IDHHuman low-grade gliomasGenome AtlasExpression levelsExpression ratioGlycolysisGenes
2019
Deep Learning Implicitly Handles Tissue Specific Phenomena to Predict Tumor DNA Accessibility and Immune Activity
Wnuk K, Sudol J, Givechian K, Soon-Shiong P, Rabizadeh S, Szeto C, Vaske C. Deep Learning Implicitly Handles Tissue Specific Phenomena to Predict Tumor DNA Accessibility and Immune Activity. IScience 2019, 20: 119-136. PMID: 31563852, PMCID: PMC6823659, DOI: 10.1016/j.isci.2019.09.018.Peer-Reviewed Original ResearchDNA accessibilityChromatin stateOpen chromatin stateChromatin regulationSpecific tissue typesPromoter-flanking regionAccessibility landscapeCancer Genome AtlasTranscriptional eventsTissue-specific phenomenonDNA sequencesGenome AtlasTissue typesImmune pathwaysPromoterTumor progressionAccessibility patternsLung adenocarcinomaNew toolKey dynamic featuresTumor typesPathwayRegulationImmune activitySequenceAn immunogenic NSCLC microenvironment is associated with favorable survival in lung adenocarcinoma
Givechian KB, Garner C, Benz S, Song B, Rabizadeh S, Soon-Shiong P. An immunogenic NSCLC microenvironment is associated with favorable survival in lung adenocarcinoma. Oncotarget 2019, 10: 1840-1849. PMID: 30956762, PMCID: PMC6442995, DOI: 10.18632/oncotarget.26748.Peer-Reviewed Original ResearchLung squamous cell carcinomaNon-small cell lung cancerSquamous cell carcinomaLung adenocarcinomaTumor microenvironmentCell carcinomaLung cancerFavorable patient survivalImmune-excluded tumorsCell lung cancerInflamed tumor microenvironmentImmune checkpoint marker expressionLung adenocarcinoma subtypesMajor NSCLC subtypesAnti-tumor immunogenicityImmunological mechanismsFavorable survivalPrognostic effectAdenocarcinoma subtypePatient survivalSurvival outcomesNSCLC subtypesImmune cellsNSCLC microenvironmentLUSC samplesDeep learning with implicit handling of tissue-specific phenomena predicts tumor DNA accessibility and immune activity.
Wnuk, K., Sudol, J., Givechian, K., Soon-Shiong, P., Rabizadeh, S., Szeto, C., & Vaske, C. (in press). Deep learning with implicit handling of tissue-specific phenomena predicts tumor DNA accessibility and immune activity. iScience.Peer-Reviewed Original Research
2018
CAD/POLD2 gene expression is associated with poor overall survival and chemoresistance in bladder urothelial carcinoma
Givechian KB, Garner C, Garban H, Rabizadeh S, Soon-Shiong P. CAD/POLD2 gene expression is associated with poor overall survival and chemoresistance in bladder urothelial carcinoma. Oncotarget 2018, 9: 29743-29752. PMID: 30038717, PMCID: PMC6049856, DOI: 10.18632/oncotarget.25701.Peer-Reviewed Original ResearchBladder urothelial carcinomaPoor overall survivalUrothelial carcinomaOverall survivalBladder urothelial carcinoma patientsUrothelial carcinoma patientsPlatinum-based therapyMechanisms of chemoresistancePatient tumor samplesRepair genesSystemic chemotherapyFavorable survivalNucleotide excision repair genesWorse survivalCarcinoma patientsPoor survivalTherapeutic strategiesTherapy resistancePyrimidine synthesis pathwayRepair processClinical targetsTumor samplesPatientsCarcinomaDNA repair genesIdentification of an immune gene expression signature associated with favorable clinical features in Treg-enriched patient tumor samples
Givechian KB, Wnuk K, Garner C, Benz S, Garban H, Rabizadeh S, Niazi K, Soon-Shiong P. Identification of an immune gene expression signature associated with favorable clinical features in Treg-enriched patient tumor samples. Npj Genomic Medicine 2018, 3: 14. PMID: 29928512, PMCID: PMC5998068, DOI: 10.1038/s41525-018-0054-7.Peer-Reviewed Original ResearchFavorable clinical featuresTumor microenvironmentTumor samplesGene signatureClinical featuresT cellsImmune gene expression signatureAntitumor activityT cell abundanceCohort of patientsFavorable clinical outcomeRegulatory T cellsAdaptive immune responsesImmunogenic tumor microenvironmentClusters of patientsPatient tumor samplesM1 macrophage subtypeTreg enrichmentTreg studiesImmunogenic tumorsGene expression signaturesOverall survivalClinical outcomesClinical associationsPatient prognosis
2017
Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma
Shvartsur A, Givechian KB, Garban H, Bonavida B. Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma. Journal Of Experimental & Clinical Cancer Research 2017, 36: 62. PMID: 28476134, PMCID: PMC5420138, DOI: 10.1186/s13046-017-0535-z.Peer-Reviewed Original ResearchConceptsRaf-1 kinase inhibitor proteinPatient-derived tumor tissueMultiple myelomaMM cell linesTumor tissueNovel therapeutic molecular targetsVariable clinical responseRKIP overexpressionNovel molecular therapeutic targetsNF-κB pathwayMolecular therapeutic targetsTherapeutic molecular targetsSignificant inverse correlationCell linesComplex heterogeneous diseaseMajority of cancersStage-specific biomarkersMEK/ERK1/2Raf/MEK/ERK1/2Clinical responseOverexpression of FasEffective therapeutic regimeDisease stageMetastatic tumorsPremalignant disease