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, 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
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
2018
Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function
Levy AD, Xiao X, Shaw JE, Devi S, Katrancha SM, Bennett AM, Greer CA, Howe JR, Machida K, Koleske AJ. Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function. Cell Reports 2018, 24: 1523-1535. PMID: 30089263, PMCID: PMC6234505, DOI: 10.1016/j.celrep.2018.07.006.Peer-Reviewed Original ResearchConceptsTyrosine phosphatase SHP2Noonan syndromePhosphatase SHP2Regulatory proteinsSHP2Recombinant GluN1Nck2Receptor functionNMDA receptor functionNMDAR functionGluN2B functionMutationsNMDAR dysfunctionNeuron functionNS miceGluN1ProteinAllelesNMDA receptorsDiheteromersReceptor kineticsReduced contributionsFunctionHyperactivationMice
2016
Low-dose dasatinib rescues cardiac function in Noonan syndrome
Yi JS, Huang Y, Kwaczala AT, Kuo IY, Ehrlich BE, Campbell SG, Giordano FJ, Bennett AM. Low-dose dasatinib rescues cardiac function in Noonan syndrome. JCI Insight 2016, 1: e90220. PMID: 27942593, PMCID: PMC5135272, DOI: 10.1172/jci.insight.90220.Peer-Reviewed Original ResearchConceptsNoonan syndromeSrc homology 2 domain-containing protein tyrosine phosphatase 2NS miceLow-dose dasatinib treatmentLow-dose dasatinibTyrosine kinase inhibitorsHearts of miceAutosomal dominant disorderCommon targetCardiac fibrosisDasatinib treatmentCardiac functionCardiomyocyte contractilityLow doseCardiac abnormalitiesShort statureNS casesNSML miceCommon autosomal dominant disorderMultiple lentiginesCraniofacial dysmorphismKinase inhibitorsMiceDasatinibProtein zero