[et_pb_section fb_built=”1″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ _module_preset=”default” min_height=”53px” custom_margin=”|auto|-77px|auto||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_post_title meta=”off” featured_image=”off” _builder_version=”4.16″ _module_preset=”default” custom_margin=”||9px|||” global_colors_info=”{}”][\/et_pb_post_title][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_2,1_2″ _builder_version=”4.16″ _module_preset=”default” min_height=”740.8px” custom_margin=”|auto|-3px|auto||” custom_padding=”0px||0px|||” global_colors_info=”{}”][et_pb_column type=”1_2″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” min_height=”688px” custom_padding=”||0px|||” global_colors_info=”{}”]<\/p>\n
Myocarditis is an inflammatory disease of the myocardium responsible for ~12% of dilated cardiomyopathy. Our work, supported by grants from the NIH\/NHLBI and NIAID, utilizes an induced pluripotent stem cell platform and genomic sequencing in humans to change the paradigm of this elusive disorder from one that was previously deemed an arbitrary infectious disease to instead a human genetic condition. The research is clarifying genetic susceptibility to viral myocarditis, including \u201ctraditional\u201d viruses such as coxsackievirus B3 and the novel SARS-CoV-2 virus, and may soon allow physicians to identify who is most at risk to impact prophylaxis and management.<\/span><\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-content\/uploads\/sites\/395\/2021\/08\/New-screenshot.png” title_text=”New screenshot” _builder_version=”4.16″ _module_preset=”default” custom_padding=”||0px|||” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” min_height=”7px” custom_padding=”0px||11px|||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” custom_margin=”||10px||false|false” global_colors_info=”{}”]<\/p>\n In a specific application of this work, we are investigating the role of background human genetics in cardiac susceptibility to myocarditis following exposure to the COVID-19 virus, SARS-CoV-2<\/span><\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” min_height=”446.8px” custom_padding=”||0px|||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_blurb image=”https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-content\/uploads\/sites\/395\/2021\/09\/Figure-all-panels.jpg” content_max_width=”1100px” _builder_version=”4.16″ _module_preset=”default” header_level=”h6″ header_font_size=”1px” body_font_size=”13px” custom_margin=”-61px||-1px||false|false” custom_padding=”0px||0px||false|false” custom_css_blurb_image=”margin-bottom: 0px!important;” global_colors_info=”{}”]<\/p>\n Legend:<\/strong>\u00a0<\/span>A) SARS-CoV-2 is cardiotropic, as evidenced by viral uptake (green, Nucleocapsid protein) in representative wild-type (WT) hiPSC-CM (red, troponin T) cells (blue, nuclei) at 48 hours post infection (h.p.i); scale bar = 25\u00a0<\/span>\u03bcm. B) SARS-CoV-2 replication (measured as infectious units per mL, infU\/mL) within hiPSC-CM is blunted in the context of loss-of-function mutations in key structural cardiomyocyte genes. *\u00a0<\/span>DMD<\/em>\u00a0<\/span>vs.\u00a0<\/span>DSC2<\/em>\u00a0<\/span>p=0.01; \u2020 WT vs.\u00a0<\/span>DSC2<\/em>\u00a0<\/span>p<0.01,\u00a0<\/span>DMD<\/em>\u00a0<\/span>vs.\u00a0<\/span>DSC2<\/em>\u00a0<\/span>p=0.02; \u2021 WT vs.\u00a0<\/span>DSC2<\/em>\u00a0<\/span>p=0.02,\u00a0<\/span>DMD<\/em>\u00a0<\/span>vs.\u00a0<\/span>DSC2<\/em>\u00a0<\/span>p=0.03; # WT vs.\u00a0<\/span>DSC2<\/em>\u00a0<\/span>p<0.01,\u00a0<\/span>DMD<\/em>\u00a0<\/span>vs.\u00a0<\/span>DSC2<\/em>\u00a0<\/span>p=0.02.<\/p>\n [\/et_pb_blurb][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” min_height=”81px” custom_margin=”|auto|-30px|auto||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_divider divider_weight=”1px” _builder_version=”4.16″ _module_preset=”default” custom_margin=”-45px||-45px||false|false” custom_padding=”0px||0px||false|false” custom_padding_tablet=”” custom_padding_phone=”” custom_padding_last_edited=”on|desktop” global_colors_info=”{}”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_2,1_2″ _builder_version=”4.16″ _module_preset=”default” min_height=”330px” custom_margin=”-45px||-45px||false|false” custom_padding=”0px|||||” global_colors_info=”{}”][et_pb_column type=”1_2″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” custom_margin=”-20px||||false|false” global_colors_info=”{}”]<\/p>\n We use a genotype-first approach to investigate the penetrance, temporality and range of expression in hereditary transthyretin amyloidosis (hATTR) using Mount Sinai\u2019s BioMe<\/i>\u00a0biobank in a first-of-its-kind<\/span>\u00a0study analyzing the full spectrum of health traits linked to hATTR in a large ethnically-diverse population. This work, funded by an NIH\/NHLBI R01 grant, and additional support from industry, includes natural history studies, investigating\u00a0<\/span>predictive plasma and cardiac imaging biomarkers, and determining optimal modes of surveillance for early disease detection.<\/span><\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-content\/uploads\/sites\/395\/2021\/09\/TTR-resized.png” title_text=”TTR resized” force_fullwidth=”on” _builder_version=”4.16″ _module_preset=”default” custom_margin=”-20px||||false|false” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” custom_margin=”-92px|auto||auto||” custom_padding=”||0px|||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” custom_margin=”-28px|||||” global_colors_info=”{}”][\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” locked=”off” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_divider divider_weight=”1px” _builder_version=”4.16″ _module_preset=”default” custom_margin=”-45px||-45px||false|false” custom_padding=”0px||0px||false|false” custom_padding_tablet=”” custom_padding_phone=”” custom_padding_last_edited=”on|desktop” global_colors_info=”{}”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”2_3,1_3″ _builder_version=”4.16″ _module_preset=”default” custom_margin=”-124px|auto||auto||” global_colors_info=”{}”][et_pb_column type=”2_3″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” custom_margin=”-13px|||||” global_colors_info=”{}”]<\/p>\n Other diseases currently under investigation through the genotype-first approach include aortopathies (i.e.<\/em>\u00a0<\/span>Marfan syndrome), Long QT syndrome, heritable hemorrhagic telangiectasia and cardiomyopathies.<\/p>\n <\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-content\/uploads\/sites\/395\/2021\/09\/crop-genetics-image.png” title_text=”crop genetics image” _builder_version=”4.16″ _module_preset=”default” width=”90%” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” custom_padding=”13px|||||” locked=”off” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_divider divider_weight=”1px” _builder_version=”4.16″ _module_preset=”default” custom_margin=”-45px||-45px||false|false” custom_padding=”0px||0px||false|false” custom_padding_tablet=”” custom_padding_phone=”” custom_padding_last_edited=”on|desktop” global_colors_info=”{}”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” min_height=”376px” custom_margin=”-108px|auto||auto||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n This work includes investigations in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders, and on associated comorbidities including dysautonomia.\u00a0<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_blurb title=”Mechanisms and biomarkers of thoracic aortic aneurysm” image=”data:image\/svg+xml;base64,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” _builder_version=”4.27.4″ _module_preset=”default” hover_enabled=”0″ sticky_enabled=”0″]<\/p>\n Thoracic aortic aneurysm (TAA) is a progressive dilation of the thoracic aorta that can lead to life-threatening aortic dissection or rupture. Although inherited connective tissue disorders account for a subset of cases, the molecular mechanisms underlying the more common, apparently sporadic forms of TAA remain incompletely understood. Our work integrates single-cell RNA sequencing, spatial transcriptomics, and plasma proteomics from patients with idiopathic TAA to define the cell populations, signaling pathways, and circulating factors associated with aneurysm development and progression. By linking molecular changes within the aortic wall to biomarkers detectable in the circulation, we aim to identify mechanisms that contribute to disease and improve the ability to detect individuals at risk before catastrophic complications occur.<\/p>\n [\/et_pb_blurb][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":" Genetics of myocarditis Myocarditis is an inflammatory disease of the myocardium responsible for ~12% of dilated cardiomyopathy. Our work, supported by grants from the NIH\/NHLBI and NIAID, utilizes an induced pluripotent stem cell platform and genomic sequencing in humans to change the paradigm of this elusive disorder from one that was previously deemed an arbitrary […]<\/p>\n","protected":false},"author":475,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"class_list":["post-44","page","type-page","status-publish","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-json\/wp\/v2\/pages\/44","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-json\/wp\/v2\/users\/475"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-json\/wp\/v2\/comments?post=44"}],"version-history":[{"count":33,"href":"https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-json\/wp\/v2\/pages\/44\/revisions"}],"predecessor-version":[{"id":443,"href":"https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-json\/wp\/v2\/pages\/44\/revisions\/443"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/kontorovichlab\/wp-json\/wp\/v2\/media?parent=44"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}<\/ul>\n
Natural history\u00a0and penetrance of disease among carriers of pathogenic TTR gene variants<\/strong><\/h4>\n
Genotype-first investigation of cardiac phenotypes in Mendelian diseases:<\/strong><\/h4>\n
<\/ul>\n
Epidemiology of genetic connective tissue disorders and comorbidities<\/h4>\n