2022
Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy
Boddupalli CS, Nair S, Belinsky G, Gans J, Teeple E, Nguyen TH, Mehta S, Guo L, Kramer ML, Ruan J, Wang H, Davison M, Kumar D, Vidyadhara D, Zhang B, Klinger K, Mistry PK. Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy. ELife 2022, 11: e79830. PMID: 35972072, PMCID: PMC9381039, DOI: 10.7554/elife.79830.Peer-Reviewed Original ResearchConceptsNeuronopathic Gaucher diseaseAmelioration of neuroinflammationNK cellsGaucher diseaseSerum neurofilament light chainInvolvement of microgliaActivation of microgliaRole of microgliaProminent pathological featureNeurofilament light chainBlood-derived macrophagesRare neurodegenerative disorderGlucosylceramide synthaseNeuroinflammation pathwaysSerum NFMicroglia activationNeuronal injuryImmune infiltratesImproved survivalBrain macrophagesPathological featuresGD patientsClinical trialsMacrophage compartmentPatient management
2018
Antigen-mediated regulation in monoclonal gammopathies and myeloma
Nair S, Sng J, Boddupalli CS, Seckinger A, Chesi M, Fulciniti M, Zhang L, Rauniyar N, Lopez M, Neparidze N, Parker T, Munshi NC, Sexton R, Barlogie B, Orlowski R, Bergsagel L, Hose D, Flavell RA, Mistry PK, Meffre E, Dhodapkar MV. Antigen-mediated regulation in monoclonal gammopathies and myeloma. JCI Insight 2018, 3: e98259. PMID: 29669929, PMCID: PMC5931125, DOI: 10.1172/jci.insight.98259.Peer-Reviewed Original ResearchConceptsMultiple myelomaPlasma cellsGaucher diseaseAntigenic stimulationMonoclonal gammopathyAntigen-driven stimulationMonoclonal IgClonal IgB cell receptorSingle tumor cellsPatient cohortUndetermined significanceVivo responsivenessMalignant cloneGammopathyTumor growthMonoclonal tumorsCell receptorTumor cellsAntigenGene expression profilingStimulationClonal natureMyelomaTumors
2017
Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease
Taguchi YV, Liu J, Ruan J, Pacheco J, Zhang X, Abbasi J, Keutzer J, Mistry PK, Chandra SS. Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease. Journal Of Neuroscience 2017, 37: 9617-9631. PMID: 28847804, PMCID: PMC5628407, DOI: 10.1523/jneurosci.1525-17.2017.Peer-Reviewed Original ResearchConceptsΑ-synuclein pathologyParkinson's diseaseCommon genetic risk factorGenetic risk factorsGaucher diseaseRisk factorsPD pathologyOligomeric α-synuclein speciesPD mouse brainPathological aggregationΑ-synuclein speciesHuman cellsAttractive therapeutic targetΑ-synuclein aggregationPrevalent neurodegenerative disorderGD patientsFunction mechanismPD riskMouse linesMutantsTherapeutic targetMutationsMouse brainNeurodegenerative disordersDisease
2016
Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease
Murugesan V, Liu J, Yang R, Lin H, Lischuk A, Pastores G, Zhang X, Chuang WL, Mistry PK. Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease. Blood Cells Molecules And Diseases 2016, 68: 47-53. PMID: 28003098, PMCID: PMC5468511, DOI: 10.1016/j.bcmd.2016.12.002.Peer-Reviewed Original ResearchConceptsGaucher diseaseSerum levelsMelanoma BImiglucerase enzyme replacement therapyCohort of patientsEnzyme replacement therapyOverall disease severityGPNMB levelsDisease activityUntreated patientsReplacement therapyDisease miceDisease progressionIndividual patientsLarge cohortHematological diseasesStriking elevationPatientsNew biomarkersDisease pathophysiologyDisease severityDiseaseOrgan compartmentsBiomarkersDisease mechanismsGaucher disease: Progress and ongoing challenges
Mistry PK, Lopez G, Schiffmann R, Barton NW, Weinreb NJ, Sidransky E. Gaucher disease: Progress and ongoing challenges. Molecular Genetics And Metabolism 2016, 120: 8-21. PMID: 27916601, PMCID: PMC5425955, DOI: 10.1016/j.ymgme.2016.11.006.Peer-Reviewed Original ResearchConceptsGaucher diseaseFirst mutant allelePluripotent stem cell modelsInduced Pluripotent Stem Cell ModelStem cell modelImportant risk factorHigh-throughput screenEnzyme replacement therapyNational InstituteLysosomal enzyme glucocerebrosidaseRecombinant productionReplacement therapyMutant allelesClinical centersRisk factorsMouse modelThroughput screenClonal Immunoglobulin against Lysolipids in the Origin of Myeloma
Nair S, Branagan AR, Liu J, Boddupalli CS, Mistry PK, Dhodapkar MV. Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma. New England Journal Of Medicine 2016, 374: 555-561. PMID: 26863356, PMCID: PMC4804194, DOI: 10.1056/nejmoa1508808.Peer-Reviewed Original Research
2015
The Role of ARF6 in Biliary Atresia
Ningappa M, So J, Glessner J, Ashokkumar C, Ranganathan S, Min J, Higgs BW, Sun Q, Haberman K, Schmitt L, Vilarinho S, Mistry PK, Vockley G, Dhawan A, Gittes GK, Hakonarson H, Jaffe R, Subramaniam S, Shin D, Sindhi R. The Role of ARF6 in Biliary Atresia. PLOS ONE 2015, 10: e0138381. PMID: 26379158, PMCID: PMC4574480, DOI: 10.1371/journal.pone.0138381.Peer-Reviewed Original ResearchRecommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States
Balwani M, Burrow TA, Charrow J, Goker-Alpan O, Kaplan P, Kishnani PS, Mistry P, Ruskin J, Weinreb N. Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States. Molecular Genetics And Metabolism 2015, 117: 95-103. PMID: 26387627, DOI: 10.1016/j.ymgme.2015.09.002.Peer-Reviewed Original ResearchConceptsGaucher disease type 1Disease type 1Type 1Oral substrate reduction therapyGaucher diseaseFirst-line therapyFirst-line treatmentTreatment of adultsCare of patientsEnzyme replacement therapyMonitoring of patientsPanel of physiciansSubstrate reduction therapyEliglustat therapyReplacement therapyMultisystem diseaseClinical trialsReduction therapyBone marrowTherapySkeletal diseaseEliglustatLysosomes of cellsDeficient activityDisease
2014
Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation
Nair S, Boddupalli CS, Verma R, Liu J, Yang R, Pastores GM, Mistry PK, Dhodapkar MV. Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation. Blood 2014, 125: 1256-1271. PMID: 25499455, PMCID: PMC4335081, DOI: 10.1182/blood-2014-09-600270.Peer-Reviewed Original ResearchConceptsI NKT cellsNKT cellsB cell activationT cellsB cellsTetramer-positive T cellsType II natural killer T cellsT cell receptor usageType I NKT cellsType II NKT cellsNatural killer T cellsFollicular helper phenotypeGD mouse modelMetabolic lipid disordersKiller T cellsB cell immunityGerminal center B cellsB-cell malignanciesAntilipid antibodiesDisease activityCytokine profileChronic inflammationHelper phenotypeHumoral immunityCognate helpGlucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease
Mistry PK, Liu J, Sun L, Chuang WL, Yuen T, Yang R, Lu P, Zhang K, Li J, Keutzer J, Stachnik A, Mennone A, Boyer JL, Jain D, Brady RO, New MI, Zaidi M. Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 4934-4939. PMID: 24639522, PMCID: PMC3977292, DOI: 10.1073/pnas.1400768111.Peer-Reviewed Original ResearchConceptsType 1 Gaucher's diseaseBone formation defectGaucher diseaseSerum ceramide levelsBone formation rateEnzyme replacement therapyViable therapeutic targetGD1 patientsGBA deficiencyEnhanced elevationTherapeutic targetBone volumeMononuclear phagocytesClinical phenotypeGBA geneConditional deletionBioactive lipidsSphingosine levelsDevelopment of inhibitorsCeramide levelsLysosomal glucocerebrosidasePatientsNanomolar concentrationsDiseaseMice
2013
Gaucher Disease and Malignancy: A Model for Cancer Pathogenesis in an Inborn Error of Metabolism
Mistry PK, Taddei T, vom Dahl S, Rosenbloom BE. Gaucher Disease and Malignancy: A Model for Cancer Pathogenesis in an Inborn Error of Metabolism. Critical Reviews™ In Oncogenesis 2013, 18: 235-246. PMID: 23510066, PMCID: PMC4437216, DOI: 10.1615/critrevoncog.2013006145.BooksConceptsEnzyme replacement therapyCancer riskGaucher diseaseMacrophage-targeted enzyme replacement therapyChronic B-cell stimulationCancer pathogenesisType 1 Gaucher diseaseSubset of patientsT cell dysfunctionNon-hematological malignanciesOverall cancer riskRisk of cancerNovel therapeutic targetPolarization of macrophagesDeterminant of malignancyB cell stimulationAccumulation of glucosylceramideEndoplasmic reticulum stressLysosomal storage disorderImmune dysregulationChronic inflammationIncreased prevalenceReplacement therapyMultiple myelomaConsecutive cancers
2012
Gaucher disease gene GBA functions in immune regulation
Liu J, Halene S, Yang M, Iqbal J, Yang R, Mehal WZ, Chuang WL, Jain D, Yuen T, Sun L, Zaidi M, Mistry PK. Gaucher disease gene GBA functions in immune regulation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 10018-10023. PMID: 22665763, PMCID: PMC3382552, DOI: 10.1073/pnas.1200941109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDGaucher DiseaseGlucosylceramidaseImmunophenotypingMiceMice, KnockoutConceptsGaucher diseaseHematopoietic stem cellsImmune regulationDisease severityGBA geneWidespread immune dysregulationB cell recruitmentPeripheral lymphoid organsT cell maturationLyso-GL1Immune dysregulationT helperImmune defectsTh2 cytokinesEarly thymic progenitorsLymphoid organsAntigen presentationGBA deficiencyGBA mutationsSevere diseaseClassic manifestationsClinical observationsGCase deficiencyBone marrowMature thymocytesDisease-drug pairs revealed by computational genomic connectivity mapping on GBA1 deficient, Gaucher disease mice
Yuen T, Iqbal J, Zhu LL, Sun L, Lin A, Zhao H, Liu J, Mistry PK, Zaidi M. Disease-drug pairs revealed by computational genomic connectivity mapping on GBA1 deficient, Gaucher disease mice. Biochemical And Biophysical Research Communications 2012, 422: 573-577. PMID: 22588172, PMCID: PMC3377787, DOI: 10.1016/j.bbrc.2012.05.027.Peer-Reviewed Original ResearchConceptsMacrophage-directed therapiesConnectivity mappingAutoimmune diathesisDisease miceImmune cellsNew agentsMice resultsLiver cellsGlucocerebrosidase geneDrug pairsInstitute databaseDisease phenotypeMiceDisease-drug pairsDiverse populationsCMAPCellsGammopathyDysfunctionTherapyDiathesisFuture testingAlbendazoleDisease
2010
Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage
Mistry PK, Liu J, Yang M, Nottoli T, McGrath J, Jain D, Zhang K, Keutzer J, Chuang WL, Mehal WZ, Zhao H, Lin A, Mane S, Liu X, Peng YZ, Li JH, Agrawal M, Zhu LL, Blair HC, Robinson LJ, Iqbal J, Sun L, Zaidi M. Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 19473-19478. PMID: 20962279, PMCID: PMC2984187, DOI: 10.1073/pnas.1003308107.Peer-Reviewed Original ResearchConceptsType 1 Gaucher diseaseThymic T cellsGene-deficient miceOsteoblastic bone formationWorthwhile therapeutic targetDendritic cellsSevere osteoporosisAutoimmune diseasesWidespread dysfunctionCytokine measurementsT cellsCell lineagesParkinson's diseaseTherapeutic targetGBA1 geneMononuclear phagocytesGaucher diseaseGlucocerebrosidase deficiencyMolecular dysregulationDiseaseInhibitory effectBone formationMultiple cell lineagesMesenchymal cell lineagesMacrophages
2009
Protease activation during in vivo pancreatitis is dependent on calcineurin activation
Shah AU, Sarwar A, Orabi AI, Gautam S, Grant WM, Park AJ, Shah AU, Liu J, Mistry PK, Jain D, Husain SZ. Protease activation during in vivo pancreatitis is dependent on calcineurin activation. AJP Gastrointestinal And Liver Physiology 2009, 297: g967-g973. PMID: 20501444, PMCID: PMC2777459, DOI: 10.1152/ajpgi.00181.2009.Peer-Reviewed Original ResearchConceptsAcinar cellsProtease activationDependent phosphatase calcineurinHourly intraperitoneal injectionsCourse of pancreatitisAcinar cell vacuolizationCholecystokinin analogue caeruleinPhosphatase calcineurinHistological severityMyeloperoxidase activityPancreatic acinar cellsAcute pancreatitisIL-6Inhibitor FK506Pancreatic edemaSerum amylaseIntraperitoneal injectionPancreatitis inductionPancreatitis severityCalcineurin activationPancreatitisPathological riseCell vacuolizationDigestive proenzymesPremature activation