Sravan Perla, PhD, MSc
Associate Research Scientist in PharmacologyCards
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Research
Publications
2025
SHP2 genetic variants in NSML-associated RASopathies disrupt the PZR–IRX transcription factor signaling axis
Perla S, Stiegler A, Yi J, Enyenihi L, Zhang L, Riaz M, An E, Qyang Y, Boggon T, Bennett A. SHP2 genetic variants in NSML-associated RASopathies disrupt the PZR–IRX transcription factor signaling axis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2503631122. PMID: 40854126, PMCID: PMC12415285, DOI: 10.1073/pnas.2503631122.Peer-Reviewed Original ResearchConceptsKnock-in mutationSH2 domainGenetic variantsSH2 domains of SHP2Iroquois homeoboxBinding to SHP2NSML miceProtein tyrosine phosphataseHypertrophic cardiomyopathyExpression levelsPhosphorylation-deficientProtein expressionCellular SrcTranscription factor 3Tyrosine phosphataseSHP2Protein zeroRare autosomal dominant disorderLow-dose dasatinibAutosomal dominant disorderPostnatal cardiac growthExpression of Irx3Signaling AxisIRX3Factor 3Effect of Dietary Salt Excess on DNA Methylation and Transcriptional Regulation of Human Angiotensinogen Gene Expression
Perla S, Garcia-Milan R, Mopidevi B, Jain S, Kumar A. Effect of Dietary Salt Excess on DNA Methylation and Transcriptional Regulation of Human Angiotensinogen Gene Expression. American Journal Of Hypertension 2025, hpaf150. PMID: 40808626, DOI: 10.1093/ajh/hpaf150.Peer-Reviewed Original ResearchGenome-wide association studiesDNA methylation patternsHap-IITranscriptional regulationHap-IHuman AGTMethylation patternsBinding of transcription factorsGene expressionHuman AGT genePotential gene targetsHigh-salt dietRNA-seqAssociation studiesIntron IDNA demethylationDNA methylationCpG sitesTranscriptional analysisExpressed genesTranscription factorsRisk haplotypeRNA sequencingCanonical pathwaysGene targetingAntiseizure Medications in Poststroke Seizures
Misra S, Wang S, Quinn T, Dawson J, Zelano J, Tanaka T, Grotta J, Khan E, Beriwal N, Funaro M, Perla S, Dev P, Larsson D, Hussain T, Liebeskind D, Yasuda C, Altalib H, Zaveri H, Elshahat A, Hitawala G, Wang E, Kitagawa R, Pathak A, Scalzo F, Ihara M, Sunnerhagen K, Walters M, Zhao Y, Jette N, Kasner S, Kwan P, Mishra N. Antiseizure Medications in Poststroke Seizures. Neurology 2025, 104: e210231. PMID: 39808752, DOI: 10.1212/wnl.0000000000210231.Peer-Reviewed Original ResearchConceptsRisk of biasLow-certainty evidenceModerate to high certainty evidenceNon-randomized Studies of Interventions toolDrug discontinuation ratesCochrane risk of bias toolRisk of bias toolAntiseizure medicationsSeizure recurrenceHigh risk of biasAdverse eventsCertainty of evidenceHigh-certainty evidencePoststroke seizuresModerate-certainty evidenceMortality rateRandomized Controlled TrialsDiscontinuation ratesAntiseizure medication useRecommendations AssessmentCochrane riskBias toolElectronic databasesNon-randomized studiesAssociated with high mortality rates
2024
Mitogen-Activated Protein Kinase Phosphatase-5 is Required for TGF-β Signaling Through a JNK-Dependent Pathway
Dorry S, Perla S, Bennett A. Mitogen-Activated Protein Kinase Phosphatase-5 is Required for TGF-β Signaling Through a JNK-Dependent Pathway. Molecular And Cellular Biology 2024, 45: 17-31. PMID: 39607740, PMCID: PMC11693473, DOI: 10.1080/10985549.2024.2426665.Peer-Reviewed Original ResearchMitogen-activated protein kinaseTGF-b signalingMKP-5JNK-dependent pathwayFamily of protein phosphatasesNon-canonical sitesJNK-dependent mannerP38 mitogen-activated protein kinaseMitogen-activated protein kinase phosphatase-5JNK-dependentTranscriptional activityProtein phosphatasesTranscriptome analysisRNA sequencingProtein kinaseJNK inactivationNuclear translocationSignaling activityTGF-bSmad2 phosphorylationPharmacological inhibitionDrivers of fibrosisTissue fibrosisFactor BPathwayMAPK Phosphatase-5 is required for TGF-β signaling through a JNK-dependent pathway
Samuel J Dorry, Sravan Perla, Anton M Bennett bioRxiv 2024.06.27.600976; doi: https://doi.org/10.1101/2024.06.27.600976Peer-Reviewed Original ResearchAntiseizure Medications in Post-stroke Seizures: A Systematic Review and Network Meta-analysis (P8-1.012)
Misra S, Dawson J, Kwan P, Kasner S, Grotta J, Larsson D, Tanaka T, Zaveri H, Wang S, Khan E, Funaro M, Perla S, Dev P, Hussain T, Liebeskind D, Yasuda C, Elshahat A, Hitawala G, Wang E, Kitagawa R, Pathak A, Zhao Y, Scalzo F, Ihara M, Zelano J, Sunnerhagen K, Walters M, Jette N, Quinn T, Mishra N. Antiseizure Medications in Post-stroke Seizures: A Systematic Review and Network Meta-analysis (P8-1.012). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205632.Peer-Reviewed Original Research
2023
Identification of Protein Tyrosine Phosphatase (PTP) Substrates
Perla S, Qiu B, Dorry S, Yi J, Bennett A. Identification of Protein Tyrosine Phosphatase (PTP) Substrates. Methods In Molecular Biology 2023, 2743: 123-133. PMID: 38147212, PMCID: PMC11610242, DOI: 10.1007/978-1-0716-3569-8_8.Peer-Reviewed Original ResearchEpigenetic and transcriptional regulation of the human angiotensinogen gene by high salt
Perla S, Kumar A. Epigenetic and transcriptional regulation of the human angiotensinogen gene by high salt. BioRxiv 2023 PMID: 38045346, DOI: 10.1101/2023.11.22.568343.Peer-Reviewed Original Research
2022
An Assessment of the Therapeutic Landscape for the Treatment of Heart Disease in the RASopathies
Yi JS, Perla S, Bennett AM. An Assessment of the Therapeutic Landscape for the Treatment of Heart Disease in the RASopathies. Cardiovascular Drugs And Therapy 2022, 37: 1193-1204. PMID: 35156148, PMCID: PMC11726350, DOI: 10.1007/s10557-022-07324-0.Peer-Reviewed Original ResearchConceptsRas-MAPK pathwayRAS/mitogen-activated protein kinase (MAPK) pathwayMitogen-activated protein kinase pathwayPost-developmental processesProtein kinase pathwayHypertrophic cardiomyopathyKinase pathwayRASopathy patientsDevelopmental diseasesNoonan syndromeTreatment of HCMRASopathiesCardiofaciocutaneous syndromePathwayNeurofibromatosis type 1Cardiovascular defectsValvular abnormalitiesCardiovascular manifestationsHeart diseaseClinical informationCostello syndromeCongenital heartMultiple lentiginesTherapeutic landscapeAntineoplastic drugs
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
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