2016
Connexin channels in congenital skin disorders
Lilly E, Sellitto C, Milstone LM, White TW. Connexin channels in congenital skin disorders. Seminars In Cell And Developmental Biology 2016, 50: 4-12. PMID: 26775130, PMCID: PMC4779425, DOI: 10.1016/j.semcdb.2015.11.018.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsConnexin mutationsDifferent connexin genesSubtle functional differencesConnexin functionConnexin genesDominant gainConnexin channelsHeteromeric hemichannelsSpectrum of phenotypesFunctional roleConnexin 26 mutationsFunctional differencesCongenital skin disorderMutationsGap junctionsHemichannelsCalcium regulationConnexinsConnexin 43Detailed understandingCalcium permeabilitySkin disordersPalmoplantar keratodermaDeafness syndromeGenes
2015
Gene expression profiling in pachyonychia congenita skin
Cao YA, Hickerson RP, Seegmiller BL, Grapov D, Gross MM, Bessette MR, Phinney BS, Flores MA, Speaker TJ, Vermeulen A, Bravo AA, Bruckner AL, Milstone LM, Schwartz ME, Rice RH, Kaspar RL. Gene expression profiling in pachyonychia congenita skin. Journal Of Dermatological Science 2015, 77: 156-165. PMID: 25656049, PMCID: PMC4374015, DOI: 10.1016/j.jdermsci.2015.01.001.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaTape-strip samplesPlantar skinSerine protease inhibitorNon-PC controlsPainful plantar keratodermaSkin barrier homeostasisPC patientsPatient groupControl volunteersMajor symptomsSkin biopsiesPC pathogenesisPlantar keratodermaPathogenic sequelaeSkin disordersBarrier homeostasisPatient samplesGene expression profilingKeratinocyte proliferationEnvelope proteinBiopsyMRNA analysisProtease inhibitorsSkin
2012
Inhibition of CD44 Gene Expression in Human Skin Models, Using Self-Delivery Short Interfering RNA Administered by Dissolvable Microneedle Arrays
Lara MF, González-González E, Speaker TJ, Hickerson RP, Leake D, Milstone LM, Contag CH, Kaspar RL. Inhibition of CD44 Gene Expression in Human Skin Models, Using Self-Delivery Short Interfering RNA Administered by Dissolvable Microneedle Arrays. Human Gene Therapy 2012, 23: 816-823. PMID: 22480249, PMCID: PMC3413896, DOI: 10.1089/hum.2011.211.Peer-Reviewed Original ResearchConceptsTransgenic mouse modelInhibition of CD44CD44-specific antibodiesCD44 mRNA levelsDissolvable microneedle arraysGene expressionMouse modelXenograft modelSkin disordersCD44 gene expressionHuman skin modelTarget cellsMRNA levelsHuman skin equivalentsKeratinocyte membraneTreatmentInhibitionStratum corneumTarget gene expressionSiRNASkin equivalentsEpidermal equivalentsMicroneedle arraysSkin modelExpression
2011
A Large Mutational Study in Pachyonychia Congenita
Wilson NJ, Leachman SA, Hansen CD, McMullan AC, Milstone LM, Schwartz ME, McLean WH, Hull PR, Smith FJ. A Large Mutational Study in Pachyonychia Congenita. Journal Of Investigative Dermatology 2011, 131: 1018-1024. PMID: 21326300, DOI: 10.1038/jid.2011.20.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaFrame insertion/deletion mutationsPainful palmoplantar keratodermaAdditional clinical featuresHeterozygous splice site mutationClinical featuresFollicular keratosisRare autosomal dominant skin disorderOral leukokeratosisNail dystrophyAutosomal dominant skin disorderSkin disordersHeterozygous missenseClinical diagnosisHeterozygous mutationsDominant skin disorderHotspot codonsPalmoplantar keratodermaKRT6AKRT16KRT17Splice site mutationKRT6BCongenitaPersonalized medicine
2010
Development of Quantitative Molecular Clinical End Points for siRNA Clinical Trials
Hickerson RP, Leachman SA, Pho LN, Gonzalez-Gonzalez E, Smith FJ, McLean WH, Contag CH, Leake D, Milstone LM, Kaspar RL. Development of Quantitative Molecular Clinical End Points for siRNA Clinical Trials. Journal Of Investigative Dermatology 2010, 131: 1029-1036. PMID: 21191405, DOI: 10.1038/jid.2010.372.Peer-Reviewed Original ResearchConceptsClinical trialsPachyonychia congenitaEnd pointPhase 1b clinical trialClinical end pointsRare skin disorderMolecular end pointsTypes of trialsImmune surveillancePatient-derived keratinocytesSkin disordersSustained inhibitionTreatment resultsRNAi-based therapeuticsRNA interferenceMRNA levelsTrialsTotal RNAHuman skinKeratinocyte culturesMRNAAmplifiable mRNATherapeuticsInhibitorsInhibition
2009
First-in-human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder
Leachman SA, Hickerson RP, Schwartz ME, Bullough EE, Hutcherson SL, Boucher KM, Hansen CD, Eliason MJ, Srivatsa GS, Kornbrust DJ, Smith FJ, McLean WI, Milstone LM, Kaspar RL. First-in-human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder. Molecular Therapy 2009, 18: 442-446. PMID: 19935778, PMCID: PMC2839285, DOI: 10.1038/mt.2009.273.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaPhase Ib clinical trialSubjective patient assessmentPhase Ib trialDose-escalation trialClinical efficacy measuresAutosomal dominant syndromeIb trialAdverse eventsWashout periodPatient assessmentEfficacy measuresPlantar callusClinical trialsPlantar keratodermaOpposite footSkin disordersSkin diseasesClinical settingDominant syndromeSatisfactory treatmentAdditional studiesTrialsGenetic disordersSiRNA
2008
Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita
Leachman SA, Hickerson RP, Hull PR, Smith FJ, Milstone LM, Lane EB, Bale SJ, Roop DR, McLean WH, Kaspar RL. Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita. Journal Of Dermatological Science 2008, 51: 151-157. PMID: 18495438, PMCID: PMC2587483, DOI: 10.1016/j.jdermsci.2008.04.003.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaQuantitative RT-PCRRT-PCRReal-time RT-PCRQuantitative real-time RT-PCRClinical efficacyGenetic skin disordersClinical trialsCandidate siRNASkin disordersRNA interferenceNovel therapeuticsPotent inhibitionTherapeutic siRNAsClinical applicationDisordersGenetic disordersPhysiciansCongenitaMutant allelesSiRNAHuman diseasesKeratin disordersPatientsDisease