2023
Chemiexcitation and melanin in photoreceptor disc turnover and prevention of macular degeneration
Lyu Y, Tschulakow A, Wang K, Brash D, Schraermeyer U. Chemiexcitation and melanin in photoreceptor disc turnover and prevention of macular degeneration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216935120. PMID: 37155898, PMCID: PMC10194005, DOI: 10.1073/pnas.2216935120.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumIntravitreal injectionMacular degenerationMelanolipofuscin granulesLipofuscin accumulationAge-related macular degenerationAlbino micePigmented miceMouse modelStargardt diseasePigment epitheliumRetinal pathologyRetinal degenerationNitric oxideDegenerationMiceLipofuscinPigment lipofuscinPhotoreceptor disksAlbinoAccelerated accumulationInjectionDiseasePathology
2019
Acetyl zingerone: An efficacious multifunctional ingredient for continued protection against ongoing DNA damage in melanocytes after sun exposure ends
Chaudhuri RK, Meyer T, Premi S, Brash D. Acetyl zingerone: An efficacious multifunctional ingredient for continued protection against ongoing DNA damage in melanocytes after sun exposure ends. International Journal Of Cosmetic Science 2019, 42: 36-45. PMID: 31538664, PMCID: PMC7004018, DOI: 10.1111/ics.12582.Peer-Reviewed Original ResearchConceptsSun exposureSolar-simulated ultraviolet radiationReactive oxygen speciesIntracellular levelsCyclobutane pyrimidine dimersΑ-tocopherolCPD formationTraditional sunscreensScavenge peroxynitriteUVR exposureOngoing DNA damageAntioxidant α-tocopherolUltraviolet radiationUVA radiationMelanocytesROS formationExposureQuench singlet oxygenUse of AZEfficacyOxygen speciesKeratinocytesDNA damageFree radicalsHoursAccelerating cancer without mutations
Brash DE. Accelerating cancer without mutations. ELife 2019, 8: e45809. PMID: 30895924, PMCID: PMC6428566, DOI: 10.7554/elife.45809.Commentaries, Editorials and Letters
2017
Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death
Anand S, Rollakanti KR, Brankov N, Brash DE, Hasan T, Maytin EV. Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death. Molecular Cancer Therapeutics 2017, 16: 1092-1101. PMID: 28336806, PMCID: PMC5497500, DOI: 10.1158/1535-7163.mct-16-0608.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiosynthetic PathwaysCarcinoma, Squamous CellCell DeathCell Line, TumorCell ProliferationCombined Modality TherapyDisease Models, AnimalFluorouracilGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHemeHumansMicePhotochemotherapyProtoporphyrinsTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsSquamous cell carcinomaActinic keratosesPhotodynamic therapyP53-null tumorsNew therapeutic approachesMol Cancer TherCell deathCell carcinomaTherapeutic responsePpIX levelsTherapeutic approachesMouse modelSkin cancerSCC precursorsHeme synthesis pathwayTumorsKeratosesDeathP53PDT efficacyInductionPretreatmentNeoadjuvantCombination approachSurgery
2015
Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure
Premi S, Wallisch S, Mano CM, Weiner AB, Bacchiocchi A, Wakamatsu K, Bechara EJ, Halaban R, Douki T, Brash DE. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science 2015, 347: 842-847. PMID: 25700512, PMCID: PMC4432913, DOI: 10.1126/science.1256022.Peer-Reviewed Original ResearchConceptsDark cyclobutane pyrimidine dimersExcited electronic statesUltraviolet photonsUV photonsElectronic statesTriplet stateSunlight-induced melanomaCytosine-containing cyclobutane pyrimidine dimersEnergy transferPhotonsPicosecondsElectronsUV exposureRadiationChemiexcitationEnergyStatePhotoproducts
2014
Enhancing the detection of barcoded reads in high throughput DNA sequencing data by controlling the false discovery rate
Buschmann T, Zhang R, Brash DE, Bystrykh LV. Enhancing the detection of barcoded reads in high throughput DNA sequencing data by controlling the false discovery rate. BMC Bioinformatics 2014, 15: 264. PMID: 25099007, PMCID: PMC4133078, DOI: 10.1186/1471-2105-15-264.Peer-Reviewed Original Research
2013
Clonal growth of human melanocytes using cell‐free extracellular matrix
Zhang R, Premi S, Kilic SS, Bacchiocchi A, Halaban R, Brash DE. Clonal growth of human melanocytes using cell‐free extracellular matrix. Pigment Cell & Melanoma Research 2013, 26: 925-927. PMID: 24034857, PMCID: PMC4086752, DOI: 10.1111/pcmr.12159.Peer-Reviewed Original Research
2009
Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia
Klein AM, Brash DE, Jones PH, Simons BD. Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 107: 270-275. PMID: 20018764, PMCID: PMC2806764, DOI: 10.1073/pnas.0909738107.Peer-Reviewed Original ResearchConceptsP53 mutationsNonmelanoma skin cancer incidenceSame cumulative doseSkin cancer incidenceUVB radiationUV-irradiated epidermisP53 tumor suppressor geneP53-mutant clonesCumulative doseCancer incidenceP53 mutant cellsHigh-intensity exposureMurine epidermisPreneoplastic clonesTumor suppressor geneProgenitor cellsExposure resultsPrecancerous cellsPreneoplastic cellsHuman epidermisB radiationClones of cellsThe mysterious steps in carcinogenesis: addendum
Brash D, Cairns J. The mysterious steps in carcinogenesis: addendum. British Journal Of Cancer 2009, 101: 1490-1490. PMID: 19826429, PMCID: PMC2768438, DOI: 10.1038/sj.bjc.6605332.Commentaries, Editorials and Letters
2008
Preneoplastic lesion growth driven by the death of adjacent normal stem cells
Chao DL, Eck JT, Brash DE, Maley CC, Luebeck EG. Preneoplastic lesion growth driven by the death of adjacent normal stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 15034-15039. PMID: 18815380, PMCID: PMC2567488, DOI: 10.1073/pnas.0802211105.Peer-Reviewed Original ResearchConceptsNormal stem cellsStem cellsClonal expansionCell replicationMutant cellsNormal cell replicationMutant clonesProliferative advantageDorsal epidermisCell mutationTissue architectureClonesClone growthBiological observationsCell killingApoptosis rateReplicationMutationsGrowth rateCellsGrowthNormal territoriesApoptosisExponential growth modelImportant step
2007
Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling
Knezevic D, Zhang W, Rochette PJ, Brash DE. Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 11286-11291. PMID: 17586682, PMCID: PMC2040891, DOI: 10.1073/pnas.0701318104.Peer-Reviewed Original Research
2006
Keratinocyte Apoptosis in Epidermal Development and Disease
Raj D, Brash DE, Grossman D. Keratinocyte Apoptosis in Epidermal Development and Disease. Journal Of Investigative Dermatology 2006, 126: 243-257. PMID: 16418733, PMCID: PMC2291295, DOI: 10.1038/sj.jid.5700008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEpidermal developmentNormal developmental programPre-malignant cellsDevelopmental programApoptosis controlMolecular mechanismsKeratinocyte apoptosisDysfunctional apoptosisKC apoptosisApoptosisCritical roleComplex roleNew insightsCorneum formationMouse modelCarcinogenesisSkin carcinogenesisPathwayRoleProliferationCells
2005
Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-xL reduction thereby enhancing UV-light induced apoptosis
Chaturvedi V, Sitailo LA, Qin JZ, Bodner B, Denning MF, Curry J, Zhang W, Brash D, Nickoloff BJ. Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-xL reduction thereby enhancing UV-light induced apoptosis. Oncogene 2005, 24: 5299-5312. PMID: 15940268, DOI: 10.1038/sj.onc.1208650.Peer-Reviewed Original ResearchConceptsMouse modelP53 levelsP53 siRNAHuman keratinocytesMcl-1Skin cancer developmentKnockout mouse modelP53 tumor suppressor geneCultured human keratinocytesBcl-xL antiapoptotic proteinBcl-xL levelsCommon causeParadoxical responseSkin cancerAccelerated eliminationUltraviolet light exposureWild-type p53Cancer developmentTumor suppressor geneUV-induced DNA damageEpidermal responseE2F-1 levelsPrimary culturesSiRNA-based approachAbnormal cells
2004
Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin
Takeuchi S, Zhang W, Wakamatsu K, Ito S, Hearing VJ, Kraemer KH, Brash DE. Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 15076-15081. PMID: 15477596, PMCID: PMC524044, DOI: 10.1073/pnas.0403994101.Peer-Reviewed Original ResearchConceptsYellow miceTerminal deoxynucleotidyltransferase-mediated dUTP nickTUNEL-positive cellsActive caspase-3Sunburn cellsPositive cellsBlack miceSkin cancerCongenic miceMurine skinDUTP nickDNA strand breaksMiceEpidermal sheetsHair folliclesAbility of melaninCaspase-3Sensitivity of individualsApoptosisLesionsUVA radiationRed hairCell deathHair shaftSunlight UV radiationUVB-induced apoptosis drives clonal expansion during skin tumor development
Zhang W, Hanks AN, Boucher K, Florell SR, Allen SM, Alexander A, Brash DE, Grossman D. UVB-induced apoptosis drives clonal expansion during skin tumor development. Carcinogenesis 2004, 26: 249-257. PMID: 15498793, PMCID: PMC2292404, DOI: 10.1093/carcin/bgh300.Peer-Reviewed Original Research
2003
Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones
Remenyik É, Wikonkál NM, Zhang W, Paliwal V, Brash DE. Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones. Oncogene 2003, 22: 6369-6376. PMID: 14508517, DOI: 10.1038/sj.onc.1206657.Peer-Reviewed Original ResearchConceptsAntigen-specific immunityP53-mutant clonesUltraviolet BAcute regressionNatural killer T cellsKiller T cellsRag1 knockout miceChronic UVB irradiationMurine skin tumorsInduction of carcinomasSignificant differencesUVB carcinogenesisT cellsSkin tumorsKnockout micePersistence of clonesEpidermal thicknessMurine epidermisUVB irradiationEpidermal sheetsImmunityChronic irradiationGene 1MiceRegressionInactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice
Wikonkal NM, Remenyik E, Knezevic D, Zhang W, Liu M, Zhao H, Berton TR, Johnson DG, Brash DE. Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice. Nature Cell Biology 2003, 5: 655-660. PMID: 12833065, DOI: 10.1038/ncb1001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Cycle ProteinsCell SurvivalCell Transformation, NeoplasticCells, CulturedDNA DamageDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorFemaleFibroblastsGene Expression Regulation, NeoplasticGenes, SuppressorKeratinocytesMaleMiceMice, KnockoutMutationSex RatioSkin NeoplasmsTranscription FactorsTumor Suppressor Protein p53Ultraviolet RaysConceptsUVB-induced apoptosisEarly-onset tumorsDouble knockout miceTrp53-deficient miceKnockout miceCancer sensitivityUVB exposureGenetic abnormalitiesMiceKeratinocyte apoptosisProtective mechanismApoptosis defectsApoptosis resistanceApoptosisDouble knockoutApoptosis pathwayE2F1 transcription factorE2F1 functionsPrimary fibroblastsE2F1Trp53S phaseA lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen
Xue D, Shi H, Smith JD, Chen X, Noe DA, Cedervall T, Yang DD, Eynon E, Brash DE, Kashgarian M, Flavell RA, Wolin SL. A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 7503-7508. PMID: 12788971, PMCID: PMC164616, DOI: 10.1073/pnas.0832411100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensB-LymphocytesCrosses, GeneticDose-Response Relationship, RadiationGlomerulonephritis, MembranoproliferativeHeterozygoteKidneyLupus VulgarisMiceMice, Inbred C57BLMice, TransgenicModels, GeneticRibonucleoproteinsRibosomesRNARNA, Small CytoplasmicSubcellular FractionsSyndromeT-LymphocytesUltraviolet RaysConceptsRo antibodiesRo 60Complete congenital heart blockLupus-like syndromeCongenital heart blockSystemic lupus erythematosusAnti-Ro antibodiesRo proteinAnti-chromatin antibodiesPhotosensitive skin lesionsNeonatal lupusAutoimmune syndromeLupus erythematosusHeart blockCutaneous lesionsAutoantibody developmentImmune surveillanceSkin lesionsHuman autoantigensSyndromeAntibodiesMiceLupusPatientsAutoantigens
2001
Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations
Zhang W, Remenyik E, Zelterman D, Brash D, Wikonkal N. Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 13948-13953. PMID: 11707578, PMCID: PMC61147, DOI: 10.1073/pnas.241353198.Peer-Reviewed Original ResearchThe DNA Damage Signal for Mdm2 Regulation, Trp53 Induction, and Sunburn Cell Formation In Vivo Originates from Actively Transcribed Genes
Brash D, Wikonkal N, Remenyik E, van der Horst G, Friedberg E, Cheo D, van Steeg H, Westerman A, van Kranen H. The DNA Damage Signal for Mdm2 Regulation, Trp53 Induction, and Sunburn Cell Formation In Vivo Originates from Actively Transcribed Genes. Journal Of Investigative Dermatology 2001, 117: 1234-1240. PMID: 11710938, DOI: 10.1046/j.0022-202x.2001.01554.x.Peer-Reviewed Original ResearchConceptsDNA photoproductsDNA damage signalsUnrepaired DNA lesionsCell formationSpecific genome regionsTumor suppressor proteinCsb-/- miceUltraviolet-induced apoptosisNucleotide excision repair genesApoptosis signal pathwayExcision repair genesActive genesMutant cellsGenome regionsDNA repairSuppressor proteinDamage signalsMDM2 regulationWild typeDNA lesionsPrevents cellsHomozygous inactivationGenesRepair genesDNA signals