2023
Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases
Tian X, Pedigo C, Li K, Ma X, Bunda P, Pell J, Lek A, Gu J, Zhang Y, Rangel P, Li W, Schwartze E, Nagata S, Lerner G, Perincheri S, Priyadarshini A, Zhao H, Lek M, Menon M, Fu R, Ishibe S. Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases. Journal Of Clinical Investigation 2023, 133: e171237. PMID: 37847555, PMCID: PMC10721156, DOI: 10.1172/jci171237.Peer-Reviewed Original ResearchConceptsProteinuric kidney diseaseKidney diseasePodocyte lossHuman glomerular diseasesMitotic catastrophePodocyte cell cycleSevere proteinuriaCell cycle reentryKidney failureGlomerular diseaseCell cycleKidney tissueG1/S checkpointUnsuccessful repairCyclin D1Glomerular integrityIrregular nucleiTissue-specific lossMouse podocytesPodocytesAltered expressionDiseaseCyclin B1Ribosome affinity purificationMultinucleated cellsUncovering the Role of Cyclin G-Associated Kinase (GAK) in Regulating the Podocyte Cytoskeleton
Bunda P, Tian X, Inoue K, Ishibe S. Uncovering the Role of Cyclin G-Associated Kinase (GAK) in Regulating the Podocyte Cytoskeleton. Journal Of The American Society Of Nephrology 2023, 34: 302-303. DOI: 10.1681/asn.20233411s1302d.Peer-Reviewed Original Research
2022
Cell Cycle and Senescence Regulation by Podocyte Histone Deacetylase 1 and 2
Rangel P, Cross E, Liu C, Pedigo C, Tian X, Gutiérrez-Calabrés E, Nagata S, Priyadarshini A, Lerner G, Bunda P, Perincheri S, Gu J, Zhao H, Wang Y, Inoue K, Ishibe S. Cell Cycle and Senescence Regulation by Podocyte Histone Deacetylase 1 and 2. Journal Of The American Society Of Nephrology 2022, 34: 433-450. PMID: 36414418, PMCID: PMC10103311, DOI: 10.1681/asn.2022050598.Peer-Reviewed Original ResearchConceptsCell cycle entryDNA damageSenescence-associated β-galactosidase activityDouble knockout miceRole of HDACsNormal glomerular filtration barrierAssociated phenotypesP21-mediated cell cycle arrestOpen chromatin conformationGlomerular filtration barrierSevere proteinuriaKidney failureProinflammatory cytokinesCell cycle regulationHistone deacetylase 1Cell cycle arrestKi67 expressionSustained DNA damagePodocyte lossIntact expressionMice leadsPodocyte-specific lossMatrix metalloproteinasesPodocyte detachmentProteinuriaPodocyte Endocytosis in Regulating the Glomerular Filtration Barrier
Tian X, Bunda P, Ishibe S. Podocyte Endocytosis in Regulating the Glomerular Filtration Barrier. Frontiers In Medicine 2022, 9: 801837. PMID: 35223901, PMCID: PMC8866310, DOI: 10.3389/fmed.2022.801837.Peer-Reviewed Original ResearchPlasma membrane componentsHuman genetic mutationsGlomerular filtration barrierEndocytosis genesEndocytic machineryFiltration barrierTransmembrane receptorsBiological functionsVesicle formationSignaling pathwaysEndocytosisMembrane componentsPodocyte functionCellular endocytosisNovel insightsProteinuric glomerular diseasesAdjacent basement membraneGenetic mutationsFunction studiesEpithelial cellsPathwayEndothelial cell layerBasement membraneImportant roleCell layer
2021
A UVB-responsive common variant at chromosome band 7p21.1 confers tanning response and melanoma risk via regulation of the aryl hydrocarbon receptor, AHR
Xu M, Mehl L, Zhang T, Thakur R, Sowards H, Myers T, Jessop L, Chesi A, Johnson M, Wells A, Michael H, Bunda P, Jones K, Higson H, Hennessey R, Jermusyk A, Kovacs M, Landi M, Iles M, Goldstein A, Consortium M, Choi J, Chanock S, Grant S, Chari R, Merlino G, Law M, Brown K. A UVB-responsive common variant at chromosome band 7p21.1 confers tanning response and melanoma risk via regulation of the aryl hydrocarbon receptor, AHR. American Journal Of Human Genetics 2021, 108: 1611-1630. PMID: 34343493, PMCID: PMC8456165, DOI: 10.1016/j.ajhg.2021.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBasic Helix-Loop-Helix Transcription FactorsCarcinogenesisCarcinoma, Squamous CellChromatinChromosomes, Human, Pair 7Gene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHumansMelanocytesMelanomaPolychlorinated DibenzodioxinsPolymorphism, Single NucleotidePrimary Cell CulturePromoter Regions, GeneticReceptors, Aryl HydrocarbonSkin NeoplasmsSunbathingUltraviolet RaysConceptsGenome-wide association studiesAryl hydrocarbon receptorMelanoma genome‐wide association studiesCellular responsesFunctional variantsLikely causal genesChromatin state annotationCandidate causal variantsHydrocarbon receptorMelanoma susceptibility genesGrowth phenotypeAhR expressionCausal genesPrimary melanocytesCausal variantsLead SNPRisk lociAhR bindingAssociation studiesGrowth arrestLuciferase assaySusceptibility genesCell growthKey environmental exposuresLoci
2020
Hypothalamic oestrogen receptor alpha establishes a sexually dimorphic regulatory node of energy expenditure
van Veen JE, Kammel LG, Bunda PC, Shum M, Reid MS, Massa MG, Arneson D, Park JW, Zhang Z, Joseph AM, Hrncir H, Liesa M, Arnold AP, Yang X, Correa SM. Hypothalamic oestrogen receptor alpha establishes a sexually dimorphic regulatory node of energy expenditure. Nature Metabolism 2020, 2: 351-363. PMID: 32377634, PMCID: PMC7202561, DOI: 10.1038/s42255-020-0189-6.Peer-Reviewed Original ResearchConceptsFemale-biased expressionMale-biased expressionSex-biased expressionSingle-cell RNA transcriptomicsPrecise neuronal populationsEstrogen receptor alphaReceptor alphaGene functionVentromedial hypothalamusRegulatory nodesRNA transcriptomicsMale developmentNeuronal populationsMouse ventromedial hypothalamusSitu hybridizationEnergy homeostasisEnergy expenditureCore temperatureExpressionTachykinin-1RPRMReduced core temperatureVMH neuronsChemogenetic activationPhysical activity
2018
Partial Rescue of Ocular Pigment Cells and Structure by Inducible Ectopic Expression of Mitf-M in MITF-Deficient Mice
Michael HT, Graff-Cherry C, Chin S, Rauck C, Habtemichael AD, Bunda P, Smith T, Campos MM, Bharti K, Arnheiter H, Merlino G, Day CP. Partial Rescue of Ocular Pigment Cells and Structure by Inducible Ectopic Expression of Mitf-M in MITF-Deficient Mice. Investigative Ophthalmology & Visual Science 2018, 59: 6067-6073. PMID: 30590377, PMCID: PMC6314104, DOI: 10.1167/iovs.18-25186.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternChoroidEctopic Gene ExpressionEmbryonic DevelopmentFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGenotyping TechniquesImmunohistochemistryIntramolecular OxidoreductasesIrisMaleMelanocytesMiceMice, Inbred C57BLMice, TransgenicMicrophthalmia-Associated Transcription FactorMicrophthalmosRetinal Pigment EpitheliumReverse Transcriptase Polymerase Chain ReactionSkinConceptsMicrophthalmia transcription factorMITF-M expressionEctopic expressionEpithelium gene expressionRetinal dysplasiaNew mouse lineMouse eyeRetinal structureCutaneous melanocytesRPE structureUveal melanocytesRPE functionMiceMouse linesComplete deficiencyPigmentary genesInducible ectopic expressionMelanocytesMITF isoformsIris melanocytesMicrophthalmiaPhenotypic abnormalitiesEyesMITFPartial rescue