2020
Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency
Chu JH, Zang W, Vukmirovic M, Yan X, Adams T, DeIuliis G, Hu B, Mihaljinec A, Schupp JC, Becich MJ, Hochheiser H, Gibson KF, Chen ES, Morris A, Leader JK, Wisniewski SR, Zhang Y, Sciurba FC, Collman RG, Sandhaus R, Herzog EL, Patterson KC, Sauler M, Strange C, Kaminski N. Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency. Thorax 2020, 76: 134-143. PMID: 33303696, PMCID: PMC10794043, DOI: 10.1136/thoraxjnl-2019-214301.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisAlpha-1 antitrypsin deficiencyGene modulesGene co-expression network analysisDifferential gene expression analysisCo-expression network analysisPeripheral blood mononuclear cellsGene expression patternsPBMC gene expression patternsGene coexpression networksAATD individualsGene expression profilesGene expression analysisBronchoalveolar lavageAugmentation therapyClinical variablesAntitrypsin deficiencyGene expression assaysRNA-seqCoexpression networkGene validationExpression analysisExpression assaysWGCNA modulesExpression patterns
2015
Enhancing Autophagy with Drugs or Lung-directed Gene Therapy Reverses the Pathological Effects of Respiratory Epithelial Cell Proteinopathy*
Hidvegi T, Stolz DB, Alcorn JF, Yousem SA, Wang J, Leme AS, Houghton AM, Hale P, Ewing M, Cai H, Garchar EA, Pastore N, Annunziata P, Kaminski N, Pilewski J, Shapiro SD, Pak SC, Silverman GA, Brunetti-Pierri N, Perlmutter DH. Enhancing Autophagy with Drugs or Lung-directed Gene Therapy Reverses the Pathological Effects of Respiratory Epithelial Cell Proteinopathy*. Journal Of Biological Chemistry 2015, 290: 29742-29757. PMID: 26494620, PMCID: PMC4705969, DOI: 10.1074/jbc.m115.691253.Peer-Reviewed Original ResearchMeSH KeywordsAlpha 1-Antitrypsin DeficiencyAnimalsAutophagyDisease Models, AnimalEpithelial CellsGenetic TherapyLungMiceConceptsSpontaneous pulmonary fibrosisPulmonary fibrosisΑ1-antitrypsin ZPathological effectsSevere pulmonary fibrosisRespiratory epithelial cellsPiZ miceRestrictive deficitsActivation of autophagyLeukocyte infiltrationSurfactant protein AAnimal modelsC deficiencyFibrosisProteinopathiesSkeletal muscleEpithelial cellsIntracellular accumulationAutophagolysosomal systemLungMiceAttractive targetAutophagyDrugsRecent studiesRationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol
Moller DR, Koth LL, Maier LA, Morris A, Drake W, Rossman M, Leader JK, Collman RG, Hamzeh N, Sweiss NJ, Zhang Y, O’Neal S, Senior RM, Becich M, Hochheiser HS, Kaminski N, Wisniewski SR, Gibson KF, Group* F. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol. Annals Of The American Thoracic Society 2015, 12: 1561-1571. PMID: 26193069, PMCID: PMC4627423, DOI: 10.1513/annalsats.201503-172ot.Peer-Reviewed Original ResearchConceptsAlpha-1 antitrypsin deficiencyClinical courseLung microbiomeAntitrypsin deficiencyClinical heterogeneityPathobiology of sarcoidosisTremendous clinical heterogeneityObservational cohort studyPulmonary function testsSystemic inflammatory responsePeripheral blood changesDiagnosis of sarcoidosisSelf-administered questionnaireCohort studyBaseline visitBronchoalveolar lavageFunction testsGranulomatous inflammationSystemic diseaseSarcoidosis phenotypesUrine testingClinical bronchoscopyInflammatory responseSarcoidosis StudyPrognostic biomarkerRationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol
Strange C, Senior RM, Sciurba F, O’Neal S, Morris A, Wisniewski SR, Bowler R, Hochheiser HS, Becich MJ, Zhang Y, Leader JK, Methé BA, Kaminski N, Sandhaus RA, Group* F. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol. Annals Of The American Thoracic Society 2015, 12: 1551-1560. PMID: 26153726, PMCID: PMC4627425, DOI: 10.1513/annalsats.201503-143oc.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlpha 1-Antitrypsin DeficiencyBronchoalveolar LavageCross-Sectional StudiesExercise ToleranceFemaleGenomicsGenotypeHumansMaleMicrobiotaMiddle AgedPhenotypeProspective StudiesPulmonary Disease, Chronic ObstructivePulmonary EmphysemaResearch DesignRespiratory Function TestsSarcoidosisTomography, X-Ray ComputedConceptsAlpha-1 antitrypsin deficiencyAugmentation therapyBronchoalveolar lavageAntitrypsin deficiencyClinical presentationPiZZ individualsAlpha-1-antitrypsin augmentation therapyAlpha-1 antitrypsin genotypeChronic obstructive pulmonary disease phenotypesPulmonary function testingAge 35 yearsVariable clinical presentationCross-sectional studyAlpha-1 antitrypsinIntermediate outcome measuresPulmonary disease phenotypesUnique genetic causeExercise capacityTherapeutic trialsChest tomographyClinical symptomsCOPD pathogenesisCOPD phenotypesFunction testingCOPD Study