{"id":"https://openalex.org/W2955764872","doi":"https://doi.org/10.1161/circulationaha.118.037227","title":"Inducible Pluripotent Stem Cell\u2013Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1 -Associated Noonan Syndrome","display_name":"Inducible Pluripotent Stem Cell\u2013Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1 -Associated Noonan Syndrome","publication_year":2019,"publication_date":"2019-06-05","ids":{"openalex":"https://openalex.org/W2955764872","doi":"https://doi.org/10.1161/circulationaha.118.037227","mag":"2955764872","pmid":"https://pubmed.ncbi.nlm.nih.gov/31163979","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/6709678"},"language":"en","primary_location":{"id":"doi:10.1161/circulationaha.118.037227","doi":"https://doi.org/10.1161/circulationaha.118.037227","is_oa":false,"landing_page_url":"https://doi.org/10.1161/circulationaha.118.037227","pdf_url":null,"source":{"id":"https://openalex.org/S116251202","display_name":"Circulation","issn_l":"0009-7322","issn":["0009-7322","1524-4539"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Circulation","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","datacite","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6709678","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5045221968","display_name":"Fabrice Jaffr\u00e9","orcid":"https://orcid.org/0000-0002-4858-1954","observed_orcids":["https://orcid.org/0000-0002-4858-1954"]},"institutions":[{"id":"https://openalex.org/I1316535847","display_name":"Beth Israel Deaconess Medical Center","ror":"https://ror.org/04drvxt59","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316535847"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4387153466","display_name":"Weill Cornell Medicine","ror":"https://ror.org/02r109517","country_code":"US","type":"education","lineage":["https://openalex.org/I205783295","https://openalex.org/I4387153466"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Fabrice Jaffr\u00e9","raw_affiliation_strings":["Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center (F.J., M.I.K.)","Department of Surgery, Weill Cornell Medical College, New York, NY (F.J., T.E.)","Harvard Medical School, Boston, MA (F.J., M.I.K.)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center (F.J., M.I.K.)","institution_ids":["https://openalex.org/I1316535847"]},{"raw_affiliation_string":"Department of Surgery, Weill Cornell Medical College, New York, NY (F.J., T.E.)","institution_ids":["https://openalex.org/I4387153466"]},{"raw_affiliation_string":"Harvard Medical School, Boston, MA (F.J., M.I.K.)","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003077515","display_name":"Clint L. Miller","orcid":"https://orcid.org/0000-0003-4276-3607","observed_orcids":["https://orcid.org/0000-0003-4276-3607"]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Clint L. Miller","raw_affiliation_strings":["Center for Public Health Genomics, Department of Public Health Sciences, Biochemistry and Molecular Genetics, and Biomedical Engineering, University of Virginia, Charlottesville (C.L.M.)","Clint L. Miller Center for Public Health Genomics, Department of Public Health Sciences, Biochemistry and Molecular Genetics, and Biomedical Engineering, University of Virginia, Charlottesville (C.L.M.)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Public Health Genomics, Department of Public Health Sciences, Biochemistry and Molecular Genetics, and Biomedical Engineering, University of Virginia, Charlottesville (C.L.M.)","institution_ids":["https://openalex.org/I51556381"]},{"raw_affiliation_string":"Clint L. Miller Center for Public Health Genomics, Department of Public Health Sciences, Biochemistry and Molecular Genetics, and Biomedical Engineering, University of Virginia, Charlottesville (C.L.M.)","institution_ids":["https://openalex.org/I51556381"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032999874","display_name":"Anne Sch\u00e4nzer","orcid":"https://orcid.org/0000-0002-2014-2028","observed_orcids":["https://orcid.org/0000-0002-2014-2028"]},"institutions":[{"id":"https://openalex.org/I200763008","display_name":"Justus-Liebig-Universit\u00e4t Gie\u00dfen","ror":"https://ror.org/033eqas34","country_code":"DE","type":"education","lineage":["https://openalex.org/I200763008"]},{"id":"https://openalex.org/I268975460","display_name":"Universit\u00e4tsklinikum Gie\u00dfen und Marburg","ror":"https://ror.org/032nzv584","country_code":"DE","type":"healthcare","lineage":["https://openalex.org/I268975460"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Anne Sch\u00e4nzer","raw_affiliation_strings":["Institute of Neuropathology (A.S.), University Hospital Giessen, Justus Liebig University Giessen, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Neuropathology (A.S.), University Hospital Giessen, Justus Liebig University Giessen, Germany","institution_ids":["https://openalex.org/I200763008","https://openalex.org/I268975460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003411069","display_name":"Todd Evans","orcid":"https://orcid.org/0000-0002-7148-9849","observed_orcids":["https://orcid.org/0000-0002-7148-9849"]},"institutions":[{"id":"https://openalex.org/I4387153466","display_name":"Weill Cornell Medicine","ror":"https://ror.org/02r109517","country_code":"US","type":"education","lineage":["https://openalex.org/I205783295","https://openalex.org/I4387153466"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Todd Evans","raw_affiliation_strings":["Department of Surgery, Weill Cornell Medical College, New York, NY (F.J., T.E.)","Todd Evans Department of Surgery, Weill Cornell Medical College, New York, NY (F.J., T.E.)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Surgery, Weill Cornell Medical College, New York, NY (F.J., T.E.)","institution_ids":["https://openalex.org/I4387153466"]},{"raw_affiliation_string":"Todd Evans Department of Surgery, Weill Cornell Medical College, New York, NY (F.J., T.E.)","institution_ids":["https://openalex.org/I4387153466"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056459227","display_name":"Amy E. Roberts","orcid":"https://orcid.org/0000-0001-5827-8521","observed_orcids":["https://orcid.org/0000-0001-5827-8521"]},"institutions":[{"id":"https://openalex.org/I1288882113","display_name":"Boston Children's Hospital","ror":"https://ror.org/00dvg7y05","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1288882113"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Amy E. Roberts","raw_affiliation_strings":["Department of Cardiology, Division of Genetics, Boston Children\u2019s Hospital, MA (A.E.R.)","Amy E. Roberts Department of Cardiology, Division of Genetics, Boston Children's Hospital, MA (A.E.R.)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Cardiology, Division of Genetics, Boston Children\u2019s Hospital, MA (A.E.R.)","institution_ids":["https://openalex.org/I1288882113"]},{"raw_affiliation_string":"Amy E. Roberts Department of Cardiology, Division of Genetics, Boston Children's Hospital, MA (A.E.R.)","institution_ids":["https://openalex.org/I1288882113"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022227939","display_name":"Andreas Hahn","orcid":"https://orcid.org/0000-0003-0235-5211","observed_orcids":["https://orcid.org/0000-0003-0235-5211"]},"institutions":[{"id":"https://openalex.org/I200763008","display_name":"Justus-Liebig-Universit\u00e4t Gie\u00dfen","ror":"https://ror.org/033eqas34","country_code":"DE","type":"education","lineage":["https://openalex.org/I200763008"]},{"id":"https://openalex.org/I268975460","display_name":"Universit\u00e4tsklinikum Gie\u00dfen und Marburg","ror":"https://ror.org/032nzv584","country_code":"DE","type":"healthcare","lineage":["https://openalex.org/I268975460"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Andreas Hahn","raw_affiliation_strings":["Department of Child Neurology (A.H.), University Hospital Giessen, Justus Liebig University Giessen, Germany","Andreas Hahn Department of Child Neurology (A.H.), University Hospital Giessen, Justus Liebig University Giessen, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Child Neurology (A.H.), University Hospital Giessen, Justus Liebig University Giessen, Germany","institution_ids":["https://openalex.org/I200763008"]},{"raw_affiliation_string":"Andreas Hahn Department of Child Neurology (A.H.), University Hospital Giessen, Justus Liebig University Giessen, Germany","institution_ids":["https://openalex.org/I200763008","https://openalex.org/I268975460"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5065746893","display_name":"Maria Irene Kontaridis","orcid":"https://orcid.org/0000-0002-6121-0533","observed_orcids":["https://orcid.org/0000-0002-6121-0533"]},"institutions":[{"id":"https://openalex.org/I1316535847","display_name":"Beth Israel Deaconess Medical Center","ror":"https://ror.org/04drvxt59","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316535847"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210088652","display_name":"Masonic Medical Research Laboratory","ror":"https://ror.org/004rs4477","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210088652"]},{"id":"https://openalex.org/I4210157861","display_name":"Harvard Stem Cell Institute","ror":"https://ror.org/04kj1hn59","country_code":"US","type":"facility","lineage":["https://openalex.org/I136199984","https://openalex.org/I4210157861"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Maria I. Kontaridis","raw_affiliation_strings":["Department of Biological Chemistry and Molecular Pharmacology (M.I.K.)","Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center (F.J., M.I.K.)","Harvard Medical School, Boston, MA (F.J., M.I.K.)","Harvard Stem Cell Institute, Harvard University, Cambridge, MA (M.I.K.)","Masonic Medical Research Institute, Utica, NY (M.I.K.)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biological Chemistry and Molecular Pharmacology (M.I.K.)","institution_ids":[]},{"raw_affiliation_string":"Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center (F.J., M.I.K.)","institution_ids":["https://openalex.org/I1316535847"]},{"raw_affiliation_string":"Harvard Medical School, Boston, MA (F.J., M.I.K.)","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Harvard Stem Cell Institute, Harvard University, Cambridge, MA (M.I.K.)","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210157861"]},{"raw_affiliation_string":"Masonic Medical Research Institute, Utica, NY (M.I.K.)","institution_ids":["https://openalex.org/I4210088652"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":9,"corresponding_author_ids":["https://openalex.org/A5045221968","https://openalex.org/A5065746893"],"corresponding_institution_ids":["https://openalex.org/I1316535847","https://openalex.org/I136199984","https://openalex.org/I4210088652","https://openalex.org/I4210157861","https://openalex.org/I4387153466"],"apc_list":null,"apc_paid":null,"fwci":2.869,"has_fulltext":true,"cited_by_count":69,"citation_normalized_percentile":{"value":0.92453506,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":96,"max":99},"biblio":{"volume":"140","issue":"3","first_page":"207","last_page":"224"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.4749000072479248,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.4749000072479248,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10882","display_name":"Cardiomyopathy and Myosin Studies","score":0.31150001287460327,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11677","display_name":"Congenital heart defects research","score":0.045499999076128006,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/noonan-syndrome","display_name":"Noonan syndrome","score":0.9909999966621399},{"id":"https://openalex.org/keywords/hypertrophic-cardiomyopathy","display_name":"hypertrophic cardiomyopathy","score":0.8849999904632568},{"id":"https://openalex.org/keywords/raf1-mutation","display_name":"RAF1 mutation","score":0.8790000081062317},{"id":"https://openalex.org/keywords/erk5-signaling","display_name":"ERK5 signaling","score":0.8399999737739563},{"id":"https://openalex.org/keywords/mek1-2-signaling","display_name":"MEK1/2 signaling","score":0.9950000047683716},{"id":"https://openalex.org/keywords/induced-pluripotent-stem-cell-derived-cardiomyocytes","display_name":"iPSC-derived cardiomyocytes","score":0.843999981880188},{"id":"https://openalex.org/keywords/cardiomyocyte-hypertrophy","display_name":"cardiomyocyte hypertrophy","score":0.8579999804496765},{"id":"https://openalex.org/keywords/myofibrillar-disarray","display_name":"myofibrillar disarray","score":0.9850000143051147},{"id":"https://openalex.org/keywords/therapeutic-target","display_name":"therapeutic target","score":0.5379999876022339}],"concepts":[{"id":"https://openalex.org/C107459253","wikidata":"https://www.wikidata.org/wiki/Q674925","display_name":"Induced pluripotent stem cell","level":4,"score":0.6244552135467529},{"id":"https://openalex.org/C2776149932","wikidata":"https://www.wikidata.org/wiki/Q1543446","display_name":"Noonan syndrome","level":2,"score":0.5882782936096191},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5628259181976318},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.5559958219528198},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.47001126408576965},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.44945353269577026},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.408645898103714},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.40462759137153625},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2997053265571594},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.1780512034893036},{"id":"https://openalex.org/C145103041","wikidata":"https://www.wikidata.org/wiki/Q1151519","display_name":"Embryonic stem cell","level":3,"score":0.13940104842185974}],"mesh":[{"descriptor_ui":"D000293","descriptor_name":"Adolescent","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002312","descriptor_name":"Cardiomyopathy, Hypertrophic","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D002312","descriptor_name":"Cardiomyopathy, Hypertrophic","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002478","descriptor_name":"Cells, Cultured","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002648","descriptor_name":"Child","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009634","descriptor_name":"Noonan Syndrome","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D009634","descriptor_name":"Noonan Syndrome","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D019908","descriptor_name":"Proto-Oncogene Proteins c-raf","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D019908","descriptor_name":"Proto-Oncogene Proteins c-raf","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D032383","descriptor_name":"Myocytes, Cardiac","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D048054","descriptor_name":"Mitogen-Activated Protein Kinase 7","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D048054","descriptor_name":"Mitogen-Activated Protein Kinase 7","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048369","descriptor_name":"MAP Kinase Kinase 1","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D048369","descriptor_name":"MAP Kinase Kinase 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048370","descriptor_name":"MAP Kinase Kinase 2","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D048370","descriptor_name":"MAP Kinase Kinase 2","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D057026","descriptor_name":"Induced Pluripotent Stem Cells","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D057809","descriptor_name":"HEK293 Cells","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D064113","descriptor_name":"CRISPR-Cas Systems","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false}],"locations_count":7,"locations":[{"id":"doi:10.1161/circulationaha.118.037227","doi":"https://doi.org/10.1161/circulationaha.118.037227","is_oa":false,"landing_page_url":"https://doi.org/10.1161/circulationaha.118.037227","pdf_url":null,"source":{"id":"https://openalex.org/S116251202","display_name":"Circulation","issn_l":"0009-7322","issn":["0009-7322","1524-4539"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Circulation","raw_type":"journal-article"},{"id":"pmid:31163979","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/31163979","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Circulation","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:6709678","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6709678","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Circulation","raw_type":"Text"},{"id":"pmh:oai:figshare.com:article/9624845","doi":null,"is_oa":true,"landing_page_url":"https://figshare.com/articles/Jaffre_et_al_Circulation-2019_pdf/9624845","pdf_url":"https://figshare.com/articles/Jaffre_et_al_Circulation-2019_pdf/9624845","source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Text"},{"id":"doi:10.25376/hra.9624845","doi":"https://doi.org/10.25376/hra.9624845","is_oa":true,"landing_page_url":"https://doi.org/10.25376/hra.9624845","pdf_url":null,"source":{"id":"https://openalex.org/S7407051367","display_name":"Health Research Alliance","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210157810","host_organization_name":"Health Research Alliance","host_organization_lineage":["https://openalex.org/I4210157810"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},{"id":"doi:10.25376/hra.9624845.v1","doi":"https://doi.org/10.25376/hra.9624845.v1","is_oa":true,"landing_page_url":"https://doi.org/10.25376/hra.9624845.v1","pdf_url":null,"source":{"id":"https://openalex.org/S7407051367","display_name":"Health Research Alliance","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210157810","host_organization_name":"Health Research Alliance","host_organization_lineage":["https://openalex.org/I4210157810"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},{"id":"mag:2984561009","doi":null,"is_oa":false,"landing_page_url":"https://hra.figshare.com/articles/Jaffre_et_al_Circulation-2019_pdf/9624845","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:6709678","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6709678","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Circulation","raw_type":"Text"},"sustainable_development_goals":[{"score":0.98580002784729,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2228387263","display_name":"Role of RhoA in the Molecular Pathogenesis of Heart Disease.","funder_award_id":"R01HL102368","funder_id":"https://openalex.org/F4320337338","funder_display_name":"National Heart, Lung, and Blood Institute"},{"id":"https://openalex.org/G226884144","display_name":"A Gata456 Pipeline of Discovery","funder_award_id":"R35HL135778","funder_id":"https://openalex.org/F4320337338","funder_display_name":"National Heart, Lung, and Blood Institute"},{"id":"https://openalex.org/G4901728188","display_name":"Deciphering novel molecular mechanisms underlying hypertrophic cardiomyopathy in Noonan syndrome using iPS cells","funder_award_id":"16SDG30580000","funder_id":"https://openalex.org/F4320306230","funder_display_name":"American Heart Association"},{"id":"https://openalex.org/G6536999688","display_name":"Targeted inhibition of fibrosis for the prevention of heart failure","funder_award_id":"R01HL122238","funder_id":"https://openalex.org/F4320337338","funder_display_name":"National Heart, Lung, and Blood Institute"},{"id":"https://openalex.org/G6652573395","display_name":"Elucidating the Phosphatase-Independent Roles of PTPN11 in the Heart","funder_award_id":"R01HL114775","funder_id":"https://openalex.org/F4320337338","funder_display_name":"National Heart, Lung, and Blood Institute"},{"id":"https://openalex.org/G8077683777","display_name":"EPISTATIC REGULATORY MECHANISMS OF CORONARY HEART DISEASE RISK","funder_award_id":"R00HL125912","funder_id":"https://openalex.org/F4320337338","funder_display_name":"National Heart, Lung, and Blood Institute"}],"funders":[{"id":"https://openalex.org/F4320306078","display_name":"U.S. Department of Defense","ror":"https://ror.org/0447fe631"},{"id":"https://openalex.org/F4320306230","display_name":"American Heart Association","ror":"https://ror.org/013kjyp64"},{"id":"https://openalex.org/F4320313423","display_name":"Rare Disease Foundation","ror":"https://ror.org/05g16vg65"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320332616","display_name":"Harvard Stem Cell Institute","ror":"https://ror.org/04kj1hn59"},{"id":"https://openalex.org/F4320337338","display_name":"National Heart, Lung, and Blood Institute","ror":"https://ror.org/012pb6c26"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2955764872.pdf","grobid_xml":"https://content.openalex.org/works/W2955764872.grobid-xml"},"referenced_works_count":55,"referenced_works":["https://openalex.org/W1480816628","https://openalex.org/W1964580006","https://openalex.org/W1964829713","https://openalex.org/W1965362233","https://openalex.org/W1966823852","https://openalex.org/W1969759973","https://openalex.org/W1972095462","https://openalex.org/W1977709885","https://openalex.org/W1993477468","https://openalex.org/W2002455222","https://openalex.org/W2006466204","https://openalex.org/W2011838341","https://openalex.org/W2013695106","https://openalex.org/W2016596969","https://openalex.org/W2020286442","https://openalex.org/W2030284600","https://openalex.org/W2034246581","https://openalex.org/W2035111920","https://openalex.org/W2035936653","https://openalex.org/W2040508577","https://openalex.org/W2041687747","https://openalex.org/W2043859776","https://openalex.org/W2046822015","https://openalex.org/W2060666910","https://openalex.org/W2074089133","https://openalex.org/W2077600916","https://openalex.org/W2081612300","https://openalex.org/W2083599207","https://openalex.org/W2085100222","https://openalex.org/W2086262311","https://openalex.org/W2096847688","https://openalex.org/W2097836010","https://openalex.org/W2104640964","https://openalex.org/W2109936556","https://openalex.org/W2116690404","https://openalex.org/W2118719488","https://openalex.org/W2123078446","https://openalex.org/W2123885531","https://openalex.org/W2124301770","https://openalex.org/W2138638319","https://openalex.org/W2139180993","https://openalex.org/W2147455721","https://openalex.org/W2159664830","https://openalex.org/W2165747740","https://openalex.org/W2167380395","https://openalex.org/W2191444573","https://openalex.org/W2464791551","https://openalex.org/W2512618466","https://openalex.org/W2744381632","https://openalex.org/W2971704859","https://openalex.org/W2995901820","https://openalex.org/W2998633251","https://openalex.org/W3002143230","https://openalex.org/W3143653395","https://openalex.org/W4210729786"],"related_works":["https://openalex.org/W7204623297","https://openalex.org/W2756766634","https://openalex.org/W6945235502","https://openalex.org/W4206975308","https://openalex.org/W2906028680","https://openalex.org/W2468428619","https://openalex.org/W2341214674","https://openalex.org/W3147275622","https://openalex.org/W2016596969","https://openalex.org/W4381598825"],"abstract_inverted_index":{"BACKGROUND:":[0],"More":[1],"than":[2],"90%":[3],"of":[4,17,90,121,146,178,199,225],"individuals":[5],"with":[6,10,20,92,167],"Noonan":[7],"syndrome":[8],"(NS)":[9],"mutations":[11,35,210],"clustered":[12],"in":[13,88,115,162,170],"the":[14,71,75,85,138,191,197,203],"CR2":[15],"domain":[16],"RAF1":[18,34,116,171,209],"present":[19],"severe":[21],"and":[22,40,52,67,97,102,175,213,227],"often":[23],"lethal":[24],"hypertrophic":[25],"cardiomyopathy":[26],"(HCM).":[27],"The":[28],"signaling":[29],"pathways":[30,110,186],"by":[31,94,181,206],"which":[32,207],"NS":[33,64,93,208,226],"promote":[36],"HCM":[37,66,114,212,233],"remain":[38],"elusive,":[39],"so":[41],"far,":[42],"there":[43],"is":[44,142],"no":[45],"known":[46,158],"treatment":[47,224],"for":[48,223],"NS-associated":[49,192],"HCM.":[50,193],"METHODS:":[51],"CRISPR-Cas9-generated":[53],"isogenic":[54],"control":[55],"inducible":[56],"pluripotent":[57],"stem":[58],"cell":[59],"(iPSC)-derived":[60],"cardiomyocytes":[61,83,174],"to":[62,68,159,190],"model":[63],"RAF1-associated":[65],"further":[69],"delineate":[70],"molecular":[72,204],"mechanisms":[73,205],"underlying":[74],"disease.":[76],"RESULTS:":[77],"We":[78],"show":[79],"that":[80,187,217],"mutant":[81,117,172],"iPSC-derived":[82,118,173],"phenocopy":[84],"pathology":[86],"seen":[87],"hearts":[89],"patients":[91],"exhibiting":[95],"hypertrophy":[96],"structural":[98],"defects.":[99],"Through":[100],"pharmacological":[101],"genetic":[103],"targeting,":[104],"we":[105],"identify":[106,202],"2":[107],"perturbed":[108],"concomitant":[109],"that,":[111],"together,":[112,196],"mediate":[113],"cardiomyocytes.":[119],"Hyperactivation":[120],"mitogen-activated":[122],"protein":[123],"kinase":[124,125,132,150],"1/2":[126],"(MEK1/2),":[127],"but":[128],"not":[129,156],"extracellular":[130,148],"regulated":[131,149],"1/2,":[133],"causes":[134],"myofibrillar":[135],"disarray,":[136],"whereas":[137],"enlarged":[139],"cardiomyocyte":[140],"phenotype":[141],"a":[143,154],"direct":[144],"consequence":[145],"increased":[147],"5":[151],"(ERK5)":[152],"signaling,":[153],"pathway":[155],"previously":[157],"be":[160],"involved":[161],"NS.":[163],"RNA-sequencing":[164],"reveals":[165],"genes":[166,179],"abnormal":[168],"expression":[169],"identifies":[176],"subsets":[177],"dysregulated":[180],"aberrant":[182],"MEK1/2":[183],"or":[184],"ERK5":[185],"could":[188,218],"contribute":[189],"CONCLUSIONS:":[194],"Taken":[195],"results":[198],"our":[200],"study":[201],"cause":[211],"reveal":[214],"downstream":[215],"effectors":[216],"serve":[219],"as":[220],"therapeutic":[221],"targets":[222],"perhaps":[228],"other,":[229],"more":[230],"common,":[231],"congenital":[232],"disorders.":[234]},"counts_by_year":[{"year":2026,"cited_by_count":7},{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":12},{"year":2023,"cited_by_count":11},{"year":2022,"cited_by_count":13},{"year":2021,"cited_by_count":15},{"year":2020,"cited_by_count":4},{"year":2019,"cited_by_count":3}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2019-07-12T00:00:00"}
