2023
Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions
Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner D, Mehal W, AlcHepNet, Kluger Y, Flavell R. Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. Cell 2023, 186: 3793-3809.e26. PMID: 37562401, PMCID: PMC10544749, DOI: 10.1016/j.cell.2023.07.017.Peer-Reviewed Original ResearchConceptsMetabolic functionsSpecies-specific interactionsKey metabolic functionsCell-autonomous mechanismsNon-alcoholic fatty liver diseaseMajor metabolic hubNon-parenchymal cellsMetabolic hubHuman hepatocytesMicroenvironmental regulationHuman diseasesHuman-specific aspectsHuman pathologiesHomeostatic processesSpecies mismatchCholesterol uptakeFatty liver diseaseParacrine mannerHuman immuneBile acid conjugationSinusoidal endothelial cellsHepatic metabolic functionMouse liverEndothelial cellsCellsIL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive mice
2022
An update on ductal plate malformations and fibropolycystic diseases of the liver
Mirza H, Besse W, Somlo S, Weinreb J, Kenney B, Jain D. An update on ductal plate malformations and fibropolycystic diseases of the liver. Human Pathology 2022, 132: 102-113. PMID: 35777701, DOI: 10.1016/j.humpath.2022.06.022.Peer-Reviewed Original ResearchConceptsDuctal plate malformationLiver diseaseAdult polycystic liver diseaseAutosomal dominant polycystic kidneyFibropolycystic liver diseaseIsolated liver involvementCongenital hepatic fibrosisPolycystic liver diseaseVon Meyenburg complexesGenetic underpinningsMultiple clinical phenotypesFibropolycystic diseasePortal hypertensionCaroli's diseaseLiver involvementLiver cystsMeyenburg complexesHepatic fibrosisFibrocystic lesionsHepatocellular malignanciesCyst enlargementAbnormal organ developmentPolycystic kidneysAnimal modelsHepatocellular malignancyInflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1
2021
A humanized mouse model of chronic COVID-19
Sefik E, Israelow B, Mirza H, Zhao J, Qu R, Kaffe E, Song E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. A humanized mouse model of chronic COVID-19. Nature Biotechnology 2021, 40: 906-920. PMID: 34921308, PMCID: PMC9203605, DOI: 10.1038/s41587-021-01155-4.Peer-Reviewed Original ResearchConceptsChronic COVID-19Humanized mouse modelImmune responseMouse modelAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCOVID-19Adaptive human immune responsesInterferon-stimulated gene signaturePersistent viral RNACoronavirus 2 infectionPatient-derived antibodiesT-cell lymphopeniaHuman immune responseHyperactive immune responseCoronavirus disease 2019Inflammatory macrophage responseImmunological injuryLung pathologyCell lymphopeniaDisease 2019Severe diseaseRodent modelsInflammatory macrophages
2015
Mutations Affecting Keratin 10 Surface-Exposed Residues Highlight the Structural Basis of Phenotypic Variation in Epidermolytic Ichthyosis
Mirza H, Kumar A, Craiglow BG, Zhou J, Saraceni C, Torbeck R, Ragsdale B, Rehder P, Ranki A, Choate KA. Mutations Affecting Keratin 10 Surface-Exposed Residues Highlight the Structural Basis of Phenotypic Variation in Epidermolytic Ichthyosis. Journal Of Investigative Dermatology 2015, 135: 3041-3050. PMID: 26176760, DOI: 10.1038/jid.2015.284.Peer-Reviewed Original ResearchBimodal Influence of Vitamin D in Host Response to Systemic Candida Infection—Vitamin D Dose Matters
Lim JH, Ravikumar S, Wang YM, Thamboo TP, Ong L, Chen J, Goh JG, Tay SH, Chengchen L, Win MS, Leong W, Lau T, Foo R, Mirza H, Tan KS, Sethi S, Khoo AL, Chng WJ, Osato M, Netea MG, Wang Y, Chai LY. Bimodal Influence of Vitamin D in Host Response to Systemic Candida Infection—Vitamin D Dose Matters. The Journal Of Infectious Diseases 2015, 212: 635-644. PMID: 25612733, DOI: 10.1093/infdis/jiv033.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCandidiasisCholecalciferolCohort StudiesDose-Response Relationship, DrugGene Expression RegulationHumansInflammationInterferon-gammaLeukocytes, MononuclearMiceMice, Inbred BALB CPromoter Regions, GeneticRNA, MessengerSTAT Transcription FactorsSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsVitamin DConceptsVitamin D levelsCandida infectionsVitamin DD levelsVitamin D3 dosesVitamin D3 supplementationProinflammatory immune responseSystemic Candida infectionSuppression of SOCS3Vitamin D receptorVitamin D response elementD response elementCandidemic patientsD3 supplementationUntreated micePoor outcomeAntiinflammatory effectsFungal burdenVitamin D3Immune responseInterferon γD receptorBetter survivalDose matterBimodal influence
2014
Intra-Subtype Variation in Enteroadhesion Accounts for Differences in Epithelial Barrier Disruption and Is Associated with Metronidazole Resistance in Blastocystis Subtype-7
Wu Z, Mirza H, Tan KS. Intra-Subtype Variation in Enteroadhesion Accounts for Differences in Epithelial Barrier Disruption and Is Associated with Metronidazole Resistance in Blastocystis Subtype-7. PLOS Neglected Tropical Diseases 2014, 8: e2885. PMID: 24851944, PMCID: PMC4031124, DOI: 10.1371/journal.pntd.0002885.Peer-Reviewed Original ResearchConceptsEpithelial barrier disruptionBarrier disruptionDrug resistanceBlastocystis subtype 7Intra-subtype variationOccludin tight junction proteinsEpithelial barrier dysfunctionDiverse clinical outcomesParasite virulence factorsTight junction proteinsCaco-2 cellsClinical outcomesBarrier dysfunctionIntestinal disordersMetronidazole resistanceBlastocystis infectionSubtype 7Metronidazole susceptibilityHost responseIntestinal epitheliumEnteric pathogensNitrosative stressResistant strainsJunction proteinsLuminal stagesStrain‐Dependent Induction of Human Enterocyte Apoptosis by Blastocystis Disrupts Epithelial Barrier and ZO‐1 Organization in a Caspase 3‐ and 9‐Dependent Manner
Wu Z, Mirza H, Teo JD, Tan KS. Strain‐Dependent Induction of Human Enterocyte Apoptosis by Blastocystis Disrupts Epithelial Barrier and ZO‐1 Organization in a Caspase 3‐ and 9‐Dependent Manner. BioMed Research International 2014, 2014: 209163. PMID: 24822183, PMCID: PMC4009109, DOI: 10.1155/2014/209163.Peer-Reviewed Original ResearchConceptsEpithelial barrier compromiseEnterocyte apoptosisHuman colonic epithelial cell line Caco-2Barrier compromiseHuman intestinal epithelial barrier functionIntestinal epithelial barrier functionHuman intestineBlastocystis subtype 7Epithelial cell line Caco-2Caspase-3ST-7Epithelial barrier functionZO-1 organizationStrain-dependent inductionCell line Caco-2Caco-2 monolayersAbdominal painIntestinal symptomsPan-caspase inhibitor Z-VAD-FMKEpithelial permeabilitySubtype 7Subtype 4Epithelial barrierEpithelial resistanceBarrier function
2012
Statin pleiotropy prevents rho kinase‐mediated intestinal epithelial barrier compromise induced by Blastocystis cysteine proteases
Mirza H, Wu Z, Teo JD, Tan KS. Statin pleiotropy prevents rho kinase‐mediated intestinal epithelial barrier compromise induced by Blastocystis cysteine proteases. Cellular Microbiology 2012, 14: 1474-1484. PMID: 22587300, DOI: 10.1111/j.1462-5822.2012.01814.x.Peer-Reviewed Original ResearchConceptsZonula occludens-1Intestinal epithelial barrier functionEpithelial barrier functionEpithelial permeabilityIntestinal infectionsFluorescein isothiocyanate-dextran fluxHuman colonic epithelial monolayersTherapeutic potentialHMG-CoA reductaseHMG-CoA reductase inhibitor simvastatinBarrier functionChronic intestinal infectionCytoskeletal F-actinIntestinal epithelial permeabilityReductase inhibitor simvastatinColonic epithelial monolayersIntestinal epithelial barrierTransepithelial resistanceTight junctional ZO-1Myosin light chain phosphorylationParasite cysteine proteasesSymptomatic patientsIntestinal pathologyCysteine proteasesBlastocystis infection
2011
A Metronidazole-Resistant Isolate of Blastocystis spp. Is Susceptible to Nitric Oxide and Downregulates Intestinal Epithelial Inducible Nitric Oxide Synthase by a Novel Parasite Survival Mechanism
Mirza H, Wu Z, Kidwai F, Tan KS. A Metronidazole-Resistant Isolate of Blastocystis spp. Is Susceptible to Nitric Oxide and Downregulates Intestinal Epithelial Inducible Nitric Oxide Synthase by a Novel Parasite Survival Mechanism. Infection And Immunity 2011, 79: 5019-5026. PMID: 21930763, PMCID: PMC3232666, DOI: 10.1128/iai.05632-11.Peer-Reviewed Original ResearchConceptsInducible nitric oxide synthaseMetronidazole-resistant isolatesNitric oxide synthaseNitric oxideOxide synthaseBlastocystis infectionEpithelial inducible nitric oxide synthaseST-7Dose-dependent inhibitionHost innate responseHuman intestinal epitheliumHost defense mechanismsIntestinal epithelial cellsLuminal pathogensAbdominal painIntestinal symptomsImmunocompetent patientsST-4Caco-2 modelChronic infectionControversial pathogenesisInnate responseNO productionBlastocystis sppIntestinal epitheliumEpidemiology of rheumatoid arthritis in a tertiary care unit, Karachi, Pakistan.
Alam SM, Kidwai AA, Jafri SR, Qureshi BM, Sami A, Qureshi HH, Mirza H. Epidemiology of rheumatoid arthritis in a tertiary care unit, Karachi, Pakistan. Journal Of The Pakistan Medical Association 2011, 61: 123-6. PMID: 21375157.Peer-Reviewed Original ResearchConceptsExtra-articular manifestationsTertiary care hospitalIschemic heart diseaseRheumatoid arthritisRheumatology clinicCare hospitalHeart diseaseCardiovascular diseaseCommon extra-articular manifestationRetrospective medical chart reviewLiaquat National HospitalMedical chart reviewInterstitial lung diseaseDemographic characteristicsTertiary care unitAge 16 yearsAge group 16Years of agePre-defined criteriaExtraarticular manifestationsRA patientsChart reviewACR criteriaFemale predominanceCare unit
2010
A Rapid, High-Throughput Viability Assay for Blastocystis spp. Reveals Metronidazole Resistance and Extensive Subtype-Dependent Variations in Drug Susceptibilities
Mirza H, Teo JD, Upcroft J, Tan KS. A Rapid, High-Throughput Viability Assay for Blastocystis spp. Reveals Metronidazole Resistance and Extensive Subtype-Dependent Variations in Drug Susceptibilities. Antimicrobial Agents And Chemotherapy 2010, 55: 637-648. PMID: 21098237, PMCID: PMC3028762, DOI: 10.1128/aac.00900-10.Peer-Reviewed Original ResearchConceptsTreatment failureBlastocystis infectionBlastocystis sppNew treatment optionsDrug-resistant isolatesStandard therapyTreatment regimensTreatment optionsMetronidazole resistanceControversial pathogenesisSubtype 4Drug susceptibilityImportant subtypeDrug sensitivitySubtypesStandard antimicrobialsInfectionZoonotic subtypesViability assaysPresent studyParasitesFirst studyCotrimoxazoleRegimensFailure