{"id":"https://openalex.org/W2468428619","doi":"https://doi.org/10.1161/res.117.suppl_1.397","title":"Abstract 397: Generation of Raf1 Mutant and Crispr-cas9 Corrected Isogenic iPSC-derived Cardiomyocytes to Model Hypertrophic Cardiomyopathy in Noonan Syndrome","display_name":"Abstract 397: Generation of Raf1 Mutant and Crispr-cas9 Corrected Isogenic iPSC-derived Cardiomyocytes to Model Hypertrophic Cardiomyopathy in Noonan Syndrome","publication_year":2015,"publication_date":"2015-07-17","ids":{"openalex":"https://openalex.org/W2468428619","doi":"https://doi.org/10.1161/res.117.suppl_1.397","mag":"2468428619"},"language":"en","primary_location":{"id":"doi:10.1161/res.117.suppl_1.397","doi":"https://doi.org/10.1161/res.117.suppl_1.397","is_oa":false,"landing_page_url":"https://doi.org/10.1161/res.117.suppl_1.397","pdf_url":null,"source":{"id":"https://openalex.org/S10652568","display_name":"Circulation Research","issn_l":"0009-7330","issn":["0009-7330","1524-4571"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","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 Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"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"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Fabrice Jaffr\u00e9","raw_affiliation_strings":["Beth Israel Deaconess Med Cntr, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Beth Israel Deaconess Med Cntr, Boston, MA","institution_ids":["https://openalex.org/I1316535847"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100367482","display_name":"Gang Wang","orcid":"https://orcid.org/0009-0002-4385-4658","observed_orcids":["https://orcid.org/0009-0002-4385-4658"]},"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":"Gang Wang","raw_affiliation_strings":["Boston Children\u2019s Hosp, Boston, MA","Gang Wang"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Boston Children\u2019s Hosp, Boston, MA","institution_ids":["https://openalex.org/I1288882113"]},{"raw_affiliation_string":"Gang Wang","institution_ids":[]}]},{"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 Roberts","raw_affiliation_strings":["Boston Children\u2019s Hosp, Boston, MA","Amy Roberts"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Boston Children\u2019s Hosp, Boston, MA","institution_ids":["https://openalex.org/I1288882113"]},{"raw_affiliation_string":"Amy Roberts","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076662333","display_name":"William T. Pu","orcid":"https://orcid.org/0000-0002-4551-8079","observed_orcids":["https://orcid.org/0000-0002-4551-8079"]},"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":"William Pu","raw_affiliation_strings":["Boston Children\u2019s Hosp, Boston, MA","William Pu"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Boston Children\u2019s Hosp, Boston, MA","institution_ids":["https://openalex.org/I1288882113"]},{"raw_affiliation_string":"William Pu","institution_ids":[]}]},{"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"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Andreas Hahn","raw_affiliation_strings":["Univ Hosp Giessen, Giessen, Germany","Andreas Hahn"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Univ Hosp Giessen, Giessen, Germany","institution_ids":["https://openalex.org/I200763008"]},{"raw_affiliation_string":"Andreas Hahn","institution_ids":[]}]},{"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"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Maria Kontaridis","raw_affiliation_strings":["Beth Israel Deaconess Med Cntr, Boston, MA","Maria Kontaridis"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Beth Israel Deaconess Med Cntr, Boston, MA","institution_ids":["https://openalex.org/I1316535847"]},{"raw_affiliation_string":"Maria Kontaridis","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"117","issue":"suppl_1","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10505","display_name":"Pluripotent Stem Cells Research","score":0.7476000189781189,"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/T10505","display_name":"Pluripotent Stem Cells Research","score":0.7476000189781189,"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/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.05429999902844429,"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/T10878","display_name":"CRISPR and Genetic Engineering","score":0.0494999997317791,"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":0.9210000038146973},{"id":"https://openalex.org/keywords/hypertrophic-cardiomyopathy","display_name":"hypertrophic cardiomyopathy","score":0.9900000095367432},{"id":"https://openalex.org/keywords/raf-1","display_name":"Raf-1","score":0.9020000100135803},{"id":"https://openalex.org/keywords/rasopathies","display_name":"RASopathies","score":0.8840000033378601},{"id":"https://openalex.org/keywords/induced-pluripotent-stem-cells","display_name":"induced pluripotent stem cells","score":0.8769999742507935},{"id":"https://openalex.org/keywords/crispr-cas9-genome-editing","display_name":"CRISPR/Cas9 genome editing","score":0.8679999709129333},{"id":"https://openalex.org/keywords/isogenic-ipsc-lines","display_name":"isogenic iPSC lines","score":0.7630000114440918},{"id":"https://openalex.org/keywords/cardiomyocyte-differentiation","display_name":"cardiomyocyte differentiation","score":0.8130000233650208},{"id":"https://openalex.org/keywords/ras-mapk-pathway","display_name":"RAS/MAPK pathway","score":0.8840000033378601},{"id":"https://openalex.org/keywords/disease-modeling","display_name":"disease modeling","score":0.5519999861717224}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.794089674949646},{"id":"https://openalex.org/C107459253","wikidata":"https://www.wikidata.org/wiki/Q674925","display_name":"Induced pluripotent stem cell","level":4,"score":0.7592801451683044},{"id":"https://openalex.org/C98108389","wikidata":"https://www.wikidata.org/wiki/Q412563","display_name":"CRISPR","level":3,"score":0.5580454468727112},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.48555514216423035},{"id":"https://openalex.org/C144501496","wikidata":"https://www.wikidata.org/wiki/Q5533489","display_name":"Genome editing","level":4,"score":0.47899124026298523},{"id":"https://openalex.org/C76818968","wikidata":"https://www.wikidata.org/wiki/Q181940","display_name":"Sanger sequencing","level":4,"score":0.4608018696308136},{"id":"https://openalex.org/C2780185194","wikidata":"https://www.wikidata.org/wiki/Q1364270","display_name":"Hypertrophic cardiomyopathy","level":2,"score":0.4530269503593445},{"id":"https://openalex.org/C2776149932","wikidata":"https://www.wikidata.org/wiki/Q1543446","display_name":"Noonan syndrome","level":2,"score":0.45251041650772095},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4304138720035553},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.3212081491947174},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.24829238653182983},{"id":"https://openalex.org/C145103041","wikidata":"https://www.wikidata.org/wiki/Q1151519","display_name":"Embryonic stem cell","level":3,"score":0.14769968390464783},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1161/res.117.suppl_1.397","doi":"https://doi.org/10.1161/res.117.suppl_1.397","is_oa":false,"landing_page_url":"https://doi.org/10.1161/res.117.suppl_1.397","pdf_url":null,"source":{"id":"https://openalex.org/S10652568","display_name":"Circulation Research","issn_l":"0009-7330","issn":["0009-7330","1524-4571"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","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 Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9763000011444092,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W6945235502","https://openalex.org/W2756766634","https://openalex.org/W2955764872","https://openalex.org/W2906028680","https://openalex.org/W4206975308","https://openalex.org/W4397002365","https://openalex.org/W3161616563","https://openalex.org/W3215325664","https://openalex.org/W4403674373","https://openalex.org/W2889185961"],"abstract_inverted_index":{"Background:":[0],"Hypertrophic":[1],"cardiomyopathy":[2],"(HCM)":[3],"is":[4,22],"a":[5,57,62,133,138,224],"major":[6],"cause":[7],"of":[8,53,119,148,167,197,277,308,318],"death":[9],"in":[10,59,69,82,121,142,185,306,331],"infants":[11],"and":[12,32,104,116,164,178,215,251,268,286,300],"children.":[13],"Noonan":[14],"Syndrome":[15],"(NS),":[16],"an":[17,66,233],"autosomal":[18],"dominant":[19],"RASopathy":[20],"disorder,":[21],"characterized":[23],"by":[24,42,101,176,207,210,217,222,249,256],"multiple":[25,263],"defects,":[26],"including":[27],"short":[28],"stature,":[29],"facial":[30],"dysmorphia,":[31],"congenital":[33],"heart":[34],"defects":[35],"that":[36,45,64,79],"include":[37],"HCM.":[38,74,320],"RASopathies":[39],"are":[40,305],"caused":[41],"germ-line":[43],"mutations":[44],"affect":[46],"the":[47,76,99,114,143,153,183,186,198,204,246,253,278,315],"canonical":[48],"RAS-MAPK":[49],"pathway.":[50],"Indeed,":[51],"95%":[52],"NS":[54,92,122,134,187,295,332],"patients":[55,84],"with":[56,137,161,274],"mutation":[58,100,141,184,200,229],"Raf1":[60,93,144,188,199,238,296],",":[61],"gene":[63,239],"plays":[65],"integral":[67],"role":[68],"this":[70],"signaling":[71],"cascade,":[72],"exhibit":[73],"However,":[75],"molecular":[77,115,316],"mechanisms":[78],"elicit":[80],"HCM":[81,120,330],"these":[83,262,310],"remain":[85],"poorly":[86],"understood.":[87],"Objective:":[88],"To":[89],"generate":[90],"human":[91,294],"induced-pluripotent":[94],"stem":[95],"cells":[96,279,312],"(iPSCs),":[97],"correct":[98],"genome":[102,191],"editing":[103,192],"subsequently":[105],"differentiate":[106],"isogenic":[107,234,271,297],"iPSC":[108,159,235,264,298],"lines":[109,265,299],"into":[110,270],"cardiomyocytes":[111],"to":[112,313,328],"characterize":[113],"genetic":[117],"basis":[118,317],"patients.":[123,333],"Results:":[124],"We":[125,180,259,290],"generated":[126,232,293],"iPSCs":[127,189],"from":[128,132],"skin":[129],"fibroblasts":[130],"obtained":[131,157],"pediatric":[135],"patient":[136],"single":[139],"point":[140],"gene.":[145],"Using":[146],"electroporation":[147],"four":[149],"episomal":[150],"vectors":[151],"containing":[152],"Yamanaka":[154],"factors,":[155],"we":[156,230,304],"several":[158],"clones":[160],"normal":[162],"karyotypes":[163],"strong":[165],"expression":[166],"pluripotent":[168],"markers":[169,284],"(Nanog,":[170],"Oct4,":[171],"Lin28,":[172],"Sox2)":[173],"as":[174,243],"detected":[175],"RT-qPCR":[177,250],"immunofluorescence.":[179],"next":[181,260],"corrected":[182,267],"using":[190],"CRISPR-Cas9":[193],"nickase":[194],"technology.":[195],"Correction":[196],"was":[201,240],"determined":[202],"at":[203,245,252],"clonal":[205],"level":[206,248,255],"PCR":[208],"followed":[209],"Restriction":[211],"Fragment":[212],"Length":[213],"Polymorphism":[214],"confirmed":[216],"Sanger":[218],"sequencing.":[219],"In":[220],"addition,":[221],"inducing":[223],"Cas9":[225],"nickase-dependent":[226],"frame":[227],"shift":[228],"also":[231],"line":[236],"where":[237],"knockout":[241],"(KO),":[242],"demonstrated":[244],"RNA":[247],"protein":[254],"Western":[257],"Blot.":[258],"differentiated":[261],"(mutant,":[266],"KO)":[269],"beating":[272],"cardiomyocytes,":[273],"more":[275],">98%":[276],"positive":[280],"for":[281],"specific":[282],"cardiomyocyte":[283],"(\u03b1-actinin":[285],"cardiac":[287,311],"TroponinT).":[288],"Conclusion:":[289],"have":[291],"successfully":[292],"corresponding":[301],"cardiomyocytes.":[302],"Currently,":[303],"progress":[307],"characterizing":[309],"determine":[314],"NS-dependent":[319],"Ultimately,":[321],"our":[322],"work":[323],"should":[324],"reveal":[325],"new":[326],"targets":[327],"treat":[329]},"counts_by_year":[{"year":2018,"cited_by_count":1}],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2016-07-22T00:00:00"}