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 ResearchConceptsBlood-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 linePathology
2024
Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease
Lin Y, Zhao X, Liou B, Fannin V, Zhang W, Setchell K, Wang X, Pan D, Grabowski G, Liu C, Sun Y. Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease. Human Molecular Genetics 2024, 33: 1771-1788. PMID: 39101473, PMCID: PMC11458007, DOI: 10.1093/hmg/ddae113.Peer-Reviewed Original ResearchGaucher diseaseMutation dosageMouse modelDisease severityProgrammed cell deathRetinal gliosisBrain transcriptomic analysisGD pathogenesisPGRN deficiencyTissue fibrosisDisease progressionGrn-/- miceSevere phenotypeGlycosphingolipid accumulationTranscriptome analysisInflammatory responseGCase functionMiceCell deathShort life spanNeurobehavioral analysisDiseaseGCase activityNeurodegenerative diseasesPGRN
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
2019
Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice
Wang C, Zhang L, Ndong J, Hettinghouse A, Sun G, Chen C, Zhang C, Liu R, Liu C. Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice. Journal Of Neuroinflammation 2019, 16: 238. PMID: 31775776, PMCID: PMC6882111, DOI: 10.1186/s12974-019-1630-1.Peer-Reviewed Original ResearchConceptsBasso Mouse ScaleNeurological recoverySpinal cord injuryCord injuryWestern blottingWild-type littermate miceMacrophages/microgliaPromising therapeutic approachWeight-drop techniqueNew therapeutic targetsHuge economic burdenPro-apoptotic effectsPLGA thermosensitive hydrogelFunctional recoveryPGRN deficiencyPGRN expressionLittermate miceIntrathecal spaceProgranulin deficiencyTherapeutic approachesTherapeutic targetEconomic burdenWT controlsDay 21Day 7
2017
Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models
Wei J, Fu W, Ding Y, Hettinghouse A, Lendhey M, Schwarzkopf R, Kennedy O, Liu C. Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models. Arthritis Research & Therapy 2017, 19: 280. PMID: 29258611, PMCID: PMC5735869, DOI: 10.1186/s13075-017-1485-8.Peer-Reviewed Original ResearchConceptsTherapeutic effectOA modelPain-related markersAnti-catabolic effectsRole of progranulinDegenerative joint diseaseMurine OA modelMultiple murine modelsNew therapeutic alternativesTumor necrosis factor receptorIntra-articular deliveryNecrosis factor receptorInflammatory arthritisPGRN deficiencyOA phenotypeSafranin O stainingTherapeutic alternativeRat modelJoint diseaseOsteoarthritis progressionPreventative effectMurine modelCartilage degradationDegenerative factorsEarly osteoarthritis
2013
The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling
Zhao Y, Tian Q, Frenkel S, Liu C. The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling. Biomaterials 2013, 34: 6412-6421. PMID: 23746860, PMCID: PMC3713419, DOI: 10.1016/j.biomaterials.2013.05.030.Peer-Reviewed Original ResearchConceptsBone healing processBone formationHealing processEctopic bone formationTNF-α transgenic miceBone healingTNFR2-deficient miceRole of PGRNTreatment of fracturesTNF-α signalingEndochondral ossificationPotential molecular targetsEctopic bone formation modelInflammatory osteoclastogenesisTNF/TNFRPGRN deficiencyInflammatory conditionsDeficient miceRecombinant PGRNBone regenerationTransgenic micePGRNMiceCritical mediatorGrowth factor