2022
A general calculus of fitness landscapes finds genes under selection in cancers
Hsu TK, Asmussen J, Koire A, Choi BK, Gadhikar M, Huh E, Lin CH, Konecki D, Kim YW, Pickering C, Kimmel M, Donehower L, Frederick M, Myers JN, Katsonis P, Lichtarge O. A general calculus of fitness landscapes finds genes under selection in cancers. Genome Research 2022, 32: gr.275811.121. PMID: 35301263, PMCID: PMC9104707, DOI: 10.1101/gr.275811.121.Peer-Reviewed Original ResearchConceptsEvolution of traitsFitness landscapeGenotype-phenotype relationshipsEvolutionary relationshipsComplex traitsPositive selectionGenomic searchSpecific traitsCancer InsightsGenesGenetic variantsFunctional impactTraitsExperimental supportLandscapeVariantsPhenotypeEvolutionSelectionGenotypesCancer cohort
2021
Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis
Knitz MW, Bickett TE, Darragh LB, Oweida AJ, Bhatia S, Van Court B, Bhuvane S, Piper M, Gadwa J, Mueller AC, Nguyen D, Nangia V, Osborne DG, Bai X, Ferrara SE, Boss MK, Goodspeed A, Burchill MA, Tamburini BAJ, Chan ED, Pickering CR, Clambey ET, Karam SD. Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. Journal For ImmunoTherapy Of Cancer 2021, 9: e001955. PMID: 33883256, PMCID: PMC8061827, DOI: 10.1136/jitc-2020-001955.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalBasic-Leucine Zipper Transcription FactorsCell Line, TumorCombined Modality TherapyDendritic CellsDrug Resistance, NeoplasmHead and Neck NeoplasmsImmune Checkpoint InhibitorsImmunotherapyInterleukin-2 Receptor alpha SubunitLymphocyte DepletionMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutPhenotypeRadiation Dose HypofractionationRadiation ToleranceRepressor ProteinsSquamous Cell Carcinoma of Head and NeckT-Lymphocytes, RegulatoryTumor BurdenTumor MicroenvironmentTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsCombination radiation therapyRadiation therapyDendritic cellsLymph nodesMouse modelRadioresistant tumorsRegulatory T-cell depletionT cell effector responsesTumor-draining lymph nodesNeck squamous cell carcinomaOral squamous cell carcinoma tumorsT cell-dependent responsesSquamous cell carcinoma tumorsAnti-CD137 treatmentDC activation statusGy x 5Higher Treg numbersPlasticity of TregsAdoptive transfer studiesT-cell depletionSquamous cell carcinomaCell-dependent responsesOrthotopic mouse modelTumor necrosis factorαNew therapeutic opportunities
2017
Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors
Zhang M, Singh R, Peng S, Mazumdar T, Sambandam V, Shen L, Tong P, Li L, Kalu NN, Pickering CR, Frederick M, Myers JN, Wang J, Johnson FM. Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors. Cancer Letters 2017, 392: 71-82. PMID: 28126323, PMCID: PMC5404895, DOI: 10.1016/j.canlet.2017.01.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisCarcinoma, Squamous CellCell Cycle ProteinsCell Line, TumorCell ProliferationCheckpoint Kinase 1Checkpoint Kinase 2Dose-Response Relationship, DrugG2 Phase Cell Cycle CheckpointsGenotypeHead and Neck NeoplasmsHumansLIM Domain ProteinsMice, NudeMolecular Targeted TherapyMutationNuclear ProteinsPhenotypeProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsPteridinesPyrazolesPyrimidinesPyrimidinonesRas ProteinsRNA InterferenceSignal TransductionSmad4 ProteinSquamous Cell Carcinoma of Head and NeckThiophenesTime FactorsTransfectionTumor BurdenUreaXenograft Model Antitumor AssaysConceptsPolo-like kinase 1Cell linesLIM protein AjubaHNSCC cell linesInhibitor-induced apoptosisProtein expressionCell cycle inhibitorsCell cycle arrestKnockdown of PLK1Neck squamous cell carcinomaAjubaExogenous expressionNeck squamous cell carcinoma (HNSCC) tumorsSquamous cell carcinoma tumorsKinase 1HNSCC mouse modelSquamous cell carcinomaSubstrate inhibitionHigher drug dosesPotential candidate biomarkersGenomic alterationsMitotic inhibitorsPLK1 inhibitionSensitive cell linesMutations
2015
New DNA Methylation Markers and Global DNA Hypomethylation Are Associated with Oral Cancer Development
Foy JP, Pickering CR, Papadimitrakopoulou VA, Jelinek J, Lin SH, William WN, Frederick MJ, Wang J, Lang W, Feng L, Zhang L, Kim ES, Fan YH, Hong WK, El-Naggar AK, Lee JJ, Myers JN, Issa JP, Lippman SM, Mao L, Saintigny P. New DNA Methylation Markers and Global DNA Hypomethylation Are Associated with Oral Cancer Development. Cancer Prevention Research 2015, 8: 1027-1035. PMID: 26342026, PMCID: PMC4777304, DOI: 10.1158/1940-6207.capr-14-0179.Peer-Reviewed Original ResearchConceptsGlobal DNA hypomethylationOral squamous cell carcinomaOral premalignant lesionsDNA hypomethylationOral cancer-free survivalCancer-free survivalDNA methylation changesDNA methylation profilesPromoter methylationDNA promoter methylationGlobal DNA methylationTumor suppressor geneNew DNA methylation markersPromoter CpG sitesOSCC developmentDNA methylationMethylation changesMethylation profilesFoxi2Degree of methylationSuppressor geneCpG sitesMethylationDNA methylation markersGenes