{"id":31,"date":"2020-12-09T19:03:56","date_gmt":"2020-12-09T19:03:56","guid":{"rendered":"https:\/\/lab.research.sickkids.ca\/goldenberg\/?page_id=31"},"modified":"2021-02-26T15:45:44","modified_gmt":"2021-02-26T15:45:44","slug":"projects","status":"publish","type":"page","link":"https:\/\/lab.research.sickkids.ca\/goldenberg\/projects\/","title":{"rendered":"Projects"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"31\" class=\"elementor elementor-31\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-1540ebc6 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"1540ebc6\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-790ea8d6\" data-id=\"790ea8d6\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-a93e48a elementor-widget elementor-widget-spacer\" data-id=\"a93e48a\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-18516a9 elementor-hidden-phone elementor-widget elementor-widget-heading\" data-id=\"18516a9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h1 class=\"elementor-heading-title elementor-size-default\">Projects<\/h1>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-cd603be elementor-hidden-phone elementor-widget elementor-widget-spacer\" data-id=\"cd603be\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-bdea06f elementor-widget elementor-widget-heading\" data-id=\"bdea06f\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Inflammasome Activation in Pulmonary Arterial Hypertension<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-f23b704 elementor-widget elementor-widget-text-editor\" data-id=\"f23b704\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">Pulmonary arterial hypertension (PAH) is characterized by immune infiltration of the peri-vascular space, elevated levels of circulating cytokines, and autoimmunity. Specifically, circulating levels of IL-1\u03b2 and IL-6 are elevated in most patients and animal models of PAH. Secretion of IL-1\u03b2 largely occurs downstream of a multi-protein complex termed the inflammasome. Activated by a variety of intra- and extra-cellular stresses or pathogens, inflammasomes aggregate and recruit caspases, which are serine proteases. These caspases then cleave pro-IL-1\u03b2 into its mature form. They also cleave a protein called gasdermin D (GSDMD), which then oligomerizes and forms a large pore in the plasma membrane. IL-1\u03b2 leaves the cell through this pore, and sometimes, this pore results in the death of the host cell, termed pyroptosis.<\/span><\/p><p><span style=\"font-weight: 400\">Our lab and others have shown that inflammasomes are activated in PAH. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32917873\/\"><span style=\"text-decoration: underline\">We are actively studying the mechanism of this activation,<\/span><\/a> the cells in which it occurs, and when it arises in the context of disease. This work is providing critical information for further study and, importantly, inflammasome pathways are novel druggable targets in PAH.<\/span><\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-f31ab54 elementor-widget elementor-widget-image\" data-id=\"f31ab54\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"768\" height=\"593\" src=\"https:\/\/lab.research.sickkids.ca\/goldenberg\/wp-content\/uploads\/sites\/100\/2021\/01\/AJP-Figure-1-FINAL_image-768x593.png\" class=\"attachment-medium_large size-medium_large wp-image-86\" alt=\"Inflammasome complexes are activated by a wide range of inflammatory or infectious triggers. These triggers activate the inflammasome \u201cmediators\u201d, including Asc and caspase-1. The end \u201ceffectors\u201d of this process include the cleavage and release of IL-1, IL-18, and the pore-forming protein gasdermin D. In some conditions, this process results in cell rupture and death.\" srcset=\"https:\/\/lab.research.sickkids.ca\/goldenberg\/wp-content\/uploads\/sites\/100\/2021\/01\/AJP-Figure-1-FINAL_image-768x593.png 768w, https:\/\/lab.research.sickkids.ca\/goldenberg\/wp-content\/uploads\/sites\/100\/2021\/01\/AJP-Figure-1-FINAL_image-300x232.png 300w, https:\/\/lab.research.sickkids.ca\/goldenberg\/wp-content\/uploads\/sites\/100\/2021\/01\/AJP-Figure-1-FINAL_image-1024x791.png 1024w, https:\/\/lab.research.sickkids.ca\/goldenberg\/wp-content\/uploads\/sites\/100\/2021\/01\/AJP-Figure-1-FINAL_image-1536x1187.png 1536w, https:\/\/lab.research.sickkids.ca\/goldenberg\/wp-content\/uploads\/sites\/100\/2021\/01\/AJP-Figure-1-FINAL_image-2048x1583.png 2048w\" sizes=\"(max-width: 768px) 100vw, 768px\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Inflammasome complexes are activated by a wide range of inflammatory or infectious triggers. These triggers activate the inflammasome \u201cmediators\u201d, including Asc and caspase-1. The end \u201ceffectors\u201d of this process include the cleavage and release of IL-1, IL-18, and the pore-forming protein gasdermin D. In some conditions, this process results in cell rupture and death.<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-636ca78 elementor-widget elementor-widget-spacer\" data-id=\"636ca78\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-ec55ea4 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"ec55ea4\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-b3837fb\" data-id=\"b3837fb\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-e5ab304 elementor-widget elementor-widget-heading\" data-id=\"e5ab304\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Modeling Connective Tissue Disease Associated PAH<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-449acbd elementor-widget elementor-widget-text-editor\" data-id=\"449acbd\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">Patients with connective tissue diseases (Scleroderma, Lupus, and others) are at a very high risk of developing PAH. Additionally, their prognosis and response to treatment is much poorer than those with idiopathic disease. This area is an intensive focus of research in order to improve outcomes for this high risk cohort. Robust animal models are lacking for the study of PAH in CTD patients. We have recently described a mouse model of CTD-PAH, and are currently using it to understand the interface between the extracellular matrix, the immune system, and the lung vasculature, to better understand this important disease.<\/span><\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Projects Inflammasome Activation in Pulmonary Arterial Hypertension Pulmonary arterial hypertension (PAH) is characterized by immune infiltration of the peri-vascular space, elevated levels of circulating cytokines, and autoimmunity. Specifically, circulating levels of IL-1\u03b2 and IL-6 are elevated in most patients and animal models of PAH. Secretion of IL-1\u03b2 largely occurs downstream of a multi-protein complex termed&hellip;<\/p>\n","protected":false},"author":293,"featured_media":0,"parent":0,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-31","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.0 (Yoast SEO v27.0) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Projects - Goldenberg Lab<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/lab.research.sickkids.ca\/goldenberg\/projects\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Projects\" \/>\n<meta property=\"og:description\" content=\"Projects Inflammasome Activation in Pulmonary Arterial Hypertension Pulmonary arterial hypertension (PAH) is characterized by immune infiltration of the peri-vascular space, elevated levels of circulating cytokines, and autoimmunity. Specifically, circulating levels of IL-1\u03b2 and IL-6 are elevated in most patients and animal models of PAH. 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These triggers activate the inflammasome \u201cmediators\u201d, including Asc and caspase-1. The end \u201ceffectors\u201d of this process include the cleavage and release of IL-1, IL-18, and the pore-forming protein gasdermin D. 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