Featured Publications
PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases
Zhao X, Lin Y, Liou B, Fu W, Jian J, Fannin V, Zhang W, Setchell K, Grabowski G, Sun Y, Liu C. PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 120: e2210442120. PMID: 36574647, PMCID: PMC9910439, DOI: 10.1073/pnas.2210442120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainGaucher DiseaseGlucosylceramidaseLysosomesMiceMice, KnockoutMutationParkinson DiseaseProgranulinsConceptsBlood-brain barrierParkinson's diseaseGaucher diseasePGRN deficiencyPD-like phenotypesRelevant mouse modelRare lysosomal storage diseaseCommon neurodegenerative disorderVisceral symptomsNeurobehavioral deficitsSevere neuroinflammationPD pathologyLysosomal storage diseaseTherapeutic studiesMouse modelNeuronopathic involvementProgranulinImpaired autophagyNeurodegenerative disordersGD phenotypeEarly onsetMiceDiseaseFirst linePathologyProgranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease
Jian J, Tian Q, Hettinghouse A, Zhao S, Liu H, Wei J, Grunig G, Zhang W, Setchell K, Sun Y, Overkleeft H, Chan G, Liu C. Progranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease. EBioMedicine 2016, 13: 212-224. PMID: 27789271, PMCID: PMC5264254, DOI: 10.1016/j.ebiom.2016.10.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineDisease Models, AnimalFibroblastsGaucher DiseaseGlucosylceramidaseHSP70 Heat-Shock ProteinsHumansIntercellular Signaling Peptides and ProteinsLysosome-Associated Membrane GlycoproteinsLysosomesMiceMice, KnockoutPhenotypeProgranulinsProtein AggregatesProtein BindingRecombinant ProteinsStress, PhysiologicalConceptsGaucher diseaseLysosomal storage diseaseStorage diseaseCommon lysosomal storage diseaseNew therapeutic interventionsΒ-glucocerebrosidaseProgranulin insufficiencyAnimal modelsTherapeutic interventionsDiseasePGRNDisease phenotypePatient fibroblastsGCaseComplex-associated proteinsLysosomal localizationHSP70DeficiencyAssociation Between Progranulin and Gaucher Disease
Jian J, Zhao S, Tian QY, Liu H, Zhao Y, Chen WC, Grunig G, Torres PA, Wang BC, Zeng B, Pastores G, Tang W, Sun Y, Grabowski GA, Kong MX, Wang G, Chen Y, Liang F, Overkleeft HS, Saunders-Pullman R, Chan GL, Liu CJ. Association Between Progranulin and Gaucher Disease. EBioMedicine 2016, 11: 127-137. PMID: 27515686, PMCID: PMC5049935, DOI: 10.1016/j.ebiom.2016.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAllelesAnimalsCase-Control StudiesDisease Models, AnimalEnzyme ActivationFemaleGaucher DiseaseGene FrequencyGenetic Association StudiesGenotypeHumansIntercellular Signaling Peptides and ProteinsLysosomesMaleMiceMice, KnockoutMiddle AgedMutationPhenotypePolymorphism, Single NucleotideProgranulinsProtein TransportConceptsGD patientsHealthy controlsGaucher diseaseGRN genePGRN KO miceSerum PGRN levelsPGRN-deficient miceHealthy control samplesSerum levelsPGRN levelsGaucher-like cellsKO miceTherapeutic effectRecombinant PGRNGeneral populationPatientsAnimal modelsBone marrowGBA1 geneLysosomal localizationProgranulin geneNull micePGRNDiseaseMice
2021
Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease
Zhao X, Liberti R, Jian J, Fu W, Hettinghouse A, Sun Y, Liu C. Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease. Journal Of Molecular Medicine 2021, 99: 1639-1654. PMID: 34453183, PMCID: PMC8541919, DOI: 10.1007/s00109-021-02127-6.Peer-Reviewed Original ResearchConceptsLysosomal storage diseaseGaucher diseaseAutophagosome-lysosome fusionCommon lysosomal storage diseasePGRN deficiencyNovel therapiesAnimal modelsProgranulinLC3-IIMolecular targetsCrucial mediatorCritical moleculesStorage diseaseDiseaseAutophagic fluxC-terminal fragmentImpaired fusionPatient fibroblastsAutophagyImpairmentKey regulator
2018
Brain-penetrant heat shock protein amplifier arimoclomol enhances GCase activity in in vitro Gaucher disease models
Hettinghouse A, Liu C. Brain-penetrant heat shock protein amplifier arimoclomol enhances GCase activity in in vitro Gaucher disease models. EBioMedicine 2018, 38: 7-8. PMID: 30522930, PMCID: PMC6306393, DOI: 10.1016/j.ebiom.2018.11.052.Peer-Reviewed Original ResearchMolecular regulations and therapeutic targets of Gaucher disease
Chen Y, Sud N, Hettinghouse A, Liu C. Molecular regulations and therapeutic targets of Gaucher disease. Cytokine & Growth Factor Reviews 2018, 41: 65-74. PMID: 29699937, PMCID: PMC8108120, DOI: 10.1016/j.cytogfr.2018.04.003.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceGaucher DiseaseGlucosylceramidaseHumansLysosomesMutationConceptsGaucher diseaseHeat shock proteinsProper foldingMolecular regulationActivity of GCaseLysosomal localizationShock proteinsCommon lysosomal storage diseaseLysosomal appearanceIon channelsCalcium ion channelsLysosomal accumulationSaposin CLysosomal storage diseaseSubstrate glucosylceramideInflammatory mediatorsProinflammatory moleculesNew targetsPathogenic mechanismsTherapeutic targetGCaseNovel moleculesSmall moleculesDiseaseStorage diseaseChitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease
Jian J, Chen Y, Liberti R, Fu W, Hu W, Saunders-Pullman R, Pastores G, Chen Y, Sun Y, Grabowski G, Liu C. Chitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease. EBioMedicine 2018, 28: 251-260. PMID: 29396296, PMCID: PMC5835567, DOI: 10.1016/j.ebiom.2018.01.022.Peer-Reviewed Original ResearchConceptsGD patientsHealthy controlsGaucher diseaseDownstream moleculesExpression of CHI3L1Serum CHI3L1Serum levelsPGRN levelsTherapeutic effectClinical biomarkersPatientsPotential biomarkersNull miceCHI3L1ProgranulinElevated levelsBiomarkersWhole-genome microarraysDiseaseCHIT1Genome microarraysNovel regulatorImmunohistochemistryLevelsMice