2021
Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines
Yi JS, Perla S, Huang Y, Mizuno K, Giordano FJ, Vinks AA, Bennett AM. Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines. Cardiovascular Drugs And Therapy 2021, 36: 589-604. PMID: 33689087, PMCID: PMC9270274, DOI: 10.1007/s10557-021-07169-z.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyNSML miceDasatinib treatmentLow-dose dasatinib treatmentPK propertiesMultiple lentiginesHeart tissueDasatinib-treated miceExposure-dependent inhibitionSrc homology 2 domain-containing protein tyrosine phosphatase 2Development of HCMAssessment of markersAutosomal dominant disorderNSML patientsDasatinib administrationCardiac fibrosisEffective target engagementEffective therapyConclusionThese dataMouse modelPharmacodynamic propertiesPK parametersHCM progressionDasatinibNoonan syndrome
2020
Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines
Yi JS, Perla S, Enyenihi L, Bennett AM. Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines. JCI Insight 2020, 5 PMID: 32584792, PMCID: PMC7455087, DOI: 10.1172/jci.insight.137753.Peer-Reviewed Original ResearchConceptsProtein tyrosine phosphataseTyrosyl phosphorylationNSML micePhosphorylation-defective mutantPTPN11 mutationsS6 kinase activityPZR tyrosyl phosphorylationTyrosine phosphataseS6 kinasePathophysiological signalingKinase activityShp2 interactionMutant fibroblastsSHP2Transmembrane glycoproteinMultiple lentiginesNoonan syndromeCraniofacial defectsPTPN11 geneHeart lysatesPhosphorylationSHP2 bindingMutationsNF-κB pathwayProtein zero
2019
A polymorphism in intron I of the human angiotensinogen gene (hAGT) affects binding by HNF3 and hAGT expression and increases blood pressure in mice
Mopidevi B, Kaw MK, Sivankutty I, Jain S, Perla SK, Kumar A. A polymorphism in intron I of the human angiotensinogen gene (hAGT) affects binding by HNF3 and hAGT expression and increases blood pressure in mice. Journal Of Biological Chemistry 2019, 294: 11829-11839. PMID: 31201268, PMCID: PMC6682742, DOI: 10.1074/jbc.ra119.007715.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensinogenAnimalsBinding SitesBlood PressureCCAAT-Enhancer-Binding Protein-betaChromatinHep G2 CellsHepatocyte Nuclear Factor 3-betaHumansIntronsLinkage DisequilibriumLiverMiceMice, Inbred C57BLMice, TransgenicPolymorphism, Single NucleotideProtein BindingReceptors, GlucocorticoidReninRNA, MessengerConceptsIntron IHap-IITransgenic animalsGenome-wide association studiesHepatocyte nuclear factor 3Reporter gene constructsBlood pressureCCAAT enhancer-binding protein βEnhancer-binding protein βHuman angiotensinogen geneStrong homologyHypoxanthine-guanine phosphoribosyltransferase locusNucleotide sequenceGene constructsTranscription rateHuman renin genePromoter activityAssociation studiesHAGT expressionMain haplotypesGenesProtein βElevated blood pressureTransgenic mouse modelFactor 3
2018
Age-Related Expression of Human AT1R Variants and Associated Renal Dysfunction in Transgenic Mice
Jain S, Rana A, Jain K, Perla SK, Puri N, Kumar A. Age-Related Expression of Human AT1R Variants and Associated Renal Dysfunction in Transgenic Mice. American Journal Of Hypertension 2018, 31: 1234-1242. PMID: 30084918, PMCID: PMC6454504, DOI: 10.1093/ajh/hpy121.Peer-Reviewed Original ResearchConceptsTranscriptional regulationHap-IISingle nucleotide polymorphismsBlood pressureVivo ChIP assaysNucleotide polymorphismsTranscription factor USF2Strong transcriptional activityTg miceRenal disordersType I geneAged animalsHaplotype-dependent mannerTransgenic miceTranscriptional environmentI geneChIP assaysTranscriptional activityAssociated renal dysfunctionHigh blood pressurePro-inflammatory markersGenesPhysiological relevanceAge-related expressionAntioxidant defense