{"id":256,"date":"2020-12-22T20:12:31","date_gmt":"2020-12-22T20:12:31","guid":{"rendered":"https:\/\/lab.research.sickkids.ca\/tabori\/?page_id=256"},"modified":"2022-02-18T19:03:31","modified_gmt":"2022-02-18T19:03:31","slug":"telomeres-maintenance","status":"publish","type":"page","link":"https:\/\/lab.research.sickkids.ca\/tabori\/research\/telomeres-maintenance\/","title":{"rendered":"Telomere Maintenance"},"content":{"rendered":"<h1>Telomere Maintenance<\/h1>\n<p>Telomere maintenance is a hallmark of human cancer. In the majority of human cancer, telomere maintenance is achieved by reactivation of telomerase. <em>TERT <\/em>\u2013 a reverse transcriptase component of telomerase \u2013 is a proto-oncogene that governs the telomerase activity and is transcriptionally dysregulated in cancer. While genetic alterations including mutations affecting the <em>TERT <\/em>promoter has been described, the exact mechanism of <em>TERT <\/em>reactivation in human cancer cells remains poorly understood.<\/p>\n<p>We aim to investigate an aberrant DNA hypermethylation signature within the <em>TERT<\/em> promoter observed uniquely in human cancer. Our lab had uncovered a cancer-specific DNA hypermethylated region within the <em>TERT <\/em>promoter \u2013 defined as the <em>TERT <\/em>Hypermethylated Oncological Region (THOR) \u2013 and showed high prevalence of this epigenetic alteration in the context of human cancer.<\/p>\n<p>Currently, we are working to understand biological and clinical implications of THOR hypermethylation, leading to its potency as a therapeutic target and a diagnostic biomarker. We are also in the process of establishing a new model of differential allelic THOR hypermethylation in human cancer and how it can explain differential allelic expression of <em>TERT<\/em>.<\/p>\n<p>Together, our work provide an insight into the DNA methylation landscape of the <em>TERT <\/em>promoter, introduce a THOR-dependent <em>TERT <\/em>upregulatory mechanism, and propose therapeutic and diagnostic potential of THOR hypermethylation signature.<\/p>\n<p>&nbsp;<\/p>\n<h2 style=\"text-align: center\">Telomere Maintenance Team<\/h2>\n\n\t\t\t<style type='text\/css'>\n\t\t\t\t#gallery-1 {\n\t\t\t\t\tmargin: auto;\n\t\t\t\t}\n\t\t\t\t#gallery-1 .gallery-item {\n\t\t\t\t\tfloat: left;\n\t\t\t\t\tmargin-top: 10px;\n\t\t\t\t\ttext-align: center;\n\t\t\t\t\twidth: 33%;\n\t\t\t\t}\n\t\t\t\t#gallery-1 img {\n\t\t\t\t\tborder: 2px solid #cfcfcf;\n\t\t\t\t}\n\t\t\t\t#gallery-1 .gallery-caption {\n\t\t\t\t\tmargin-left: 0;\n\t\t\t\t}\n\t\t\t\t\/* see gallery_shortcode() in wp-includes\/media.php *\/\n\t\t\t<\/style>\n\t\t<div id='gallery-1' class='dt-gallery-container gallery galleryid-256 gallery-columns-3 gallery-size-thumbnail'><dl class='gallery-item'>\n\t\t\t\t<dt class='gallery-icon landscape'>\n\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"150\" height=\"150\" src=\"https:\/\/lab.research.sickkids.ca\/tabori\/wp-content\/uploads\/sites\/118\/2022\/01\/PCB_2017-150x150.jpg\" class=\"attachment-thumbnail size-thumbnail\" alt=\"Pedro Castelo-Branco\" aria-describedby=\"gallery-1-3174\" \/>\n\t\t\t\t<\/dt>\n\t\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-3174'>\n\t\t\t\t\t<a href=\"https:\/\/www.ualg.pt\/investigadores-da-ualg-2\">Pedro Castelo-Branco, PhD <\/a><br \/>Research Fellow\n\t\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"150\" height=\"150\" src=\"https:\/\/lab.research.sickkids.ca\/tabori\/wp-content\/uploads\/sites\/118\/2021\/01\/Nuno-150x150.jpg\" class=\"attachment-thumbnail size-thumbnail\" alt=\"Nuno Miguel Nunes\" aria-describedby=\"gallery-1-486\" \/>\n\t\t\t\t<\/dt>\n\t\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-486'>\n\t\t\t\t\t<a href=\"https:\/\/lab.research.sickkids.ca\/tabori\/team\/nuno-nunes\/\">Nuno Miguel Nunes, PhD<\/a> <br \/>\r\nResearch Fellow\n\t\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"150\" height=\"150\" src=\"https:\/\/lab.research.sickkids.ca\/tabori\/wp-content\/uploads\/sites\/118\/2021\/02\/Cindy-Resized-150x150.jpg\" class=\"attachment-thumbnail size-thumbnail\" alt=\"Cindy Zhang\" aria-describedby=\"gallery-1-2810\" \/>\n\t\t\t\t<\/dt>\n\t\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2810'>\n\t\t\t\t\t<a href=\"https:\/\/lab.research.sickkids.ca\/tabori\/team\/cindy-zhang\/\">Cindy Zhang <\/a><br \/>\r\nLab Manager\r\n\n\t\t\t\t\t<\/dd><\/dl><br style=\"clear: both\" \/>\n\t\t\t<\/div>\n\n<p>&nbsp;<\/p>\n<h3 style=\"text-align: center\">Alumni<\/h3>\n\n\t\t\t<style type='text\/css'>\n\t\t\t\t#gallery-2 {\n\t\t\t\t\tmargin: auto;\n\t\t\t\t}\n\t\t\t\t#gallery-2 .gallery-item {\n\t\t\t\t\tfloat: left;\n\t\t\t\t\tmargin-top: 10px;\n\t\t\t\t\ttext-align: center;\n\t\t\t\t\twidth: 33%;\n\t\t\t\t}\n\t\t\t\t#gallery-2 img {\n\t\t\t\t\tborder: 2px solid #cfcfcf;\n\t\t\t\t}\n\t\t\t\t#gallery-2 .gallery-caption {\n\t\t\t\t\tmargin-left: 0;\n\t\t\t\t}\n\t\t\t\t\/* see gallery_shortcode() in wp-includes\/media.php *\/\n\t\t\t<\/style>\n\t\t<div id='gallery-2' class='dt-gallery-container gallery galleryid-256 gallery-columns-3 gallery-size-thumbnail'><dl class='gallery-item'>\n\t\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t\t<a class=\"rollover\" href='https:\/\/lab.research.sickkids.ca\/tabori\/team\/dave-lee\/'><img loading=\"lazy\" decoding=\"async\" width=\"150\" height=\"150\" src=\"https:\/\/lab.research.sickkids.ca\/tabori\/wp-content\/uploads\/sites\/118\/2021\/01\/Dave-150x150.jpg\" class=\"attachment-thumbnail size-thumbnail\" alt=\"Donghyun (Dave) Lee\" aria-describedby=\"gallery-2-491\" \/><\/a>\n\t\t\t\t<\/dt>\n\t\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-2-491'>\n\t\t\t\t\t<a href=\"https:\/\/lab.research.sickkids.ca\/tabori\/team\/dave-lee\/\">Donghyun (Dave) Lee, PhD<\/a><br \/>\nPhD Candidate\n\t\t\t\t\t<\/dd><\/dl>\n\t\t\t\t<br style='clear: both' \/>\n\t\t\t<\/div>\n\n","protected":false},"excerpt":{"rendered":"<p>Telomere Maintenance Telomere maintenance is a hallmark of human cancer. In the majority of human cancer, telomere maintenance is achieved by reactivation of telomerase. TERT \u2013 a reverse transcriptase component of telomerase \u2013 is a proto-oncogene that governs the telomerase activity and is transcriptionally dysregulated in cancer. While genetic alterations including mutations affecting the TERT&hellip;<\/p>\n","protected":false},"author":356,"featured_media":0,"parent":95,"menu_order":3,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-256","page","type-page","status-publish","hentry","description-off"],"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>Telomere Maintenance - Tabori 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\/tabori\/research\/telomeres-maintenance\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Telomere Maintenance\" \/>\n<meta property=\"og:description\" content=\"Telomere Maintenance Telomere maintenance is a hallmark of human cancer. In the majority of human cancer, telomere maintenance is achieved by reactivation of telomerase. TERT \u2013 a reverse transcriptase component of telomerase \u2013 is a proto-oncogene that governs the telomerase activity and is transcriptionally dysregulated in cancer. While genetic alterations including mutations affecting the TERT&hellip;\" \/>\n<meta property=\"og:url\" content=\"https:\/\/lab.research.sickkids.ca\/tabori\/research\/telomeres-maintenance\/\" \/>\n<meta property=\"og:site_name\" content=\"Tabori Lab\" \/>\n<meta property=\"article:modified_time\" content=\"2022-02-18T19:03:31+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/lab.research.sickkids.ca\/tabori\/wp-content\/uploads\/sites\/118\/2021\/02\/Cindy-Resized-150x150.jpg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/lab.research.sickkids.ca\/tabori\/research\/telomeres-maintenance\/\",\"url\":\"https:\/\/lab.research.sickkids.ca\/tabori\/research\/telomeres-maintenance\/\",\"name\":\"Telomere Maintenance - Tabori Lab\",\"isPartOf\":{\"@id\":\"https:\/\/lab.research.sickkids.ca\/tabori\/#website\"},\"datePublished\":\"2020-12-22T20:12:31+00:00\",\"dateModified\":\"2022-02-18T19:03:31+00:00\",\"breadcrumb\":{\"@id\":\"https:\/\/lab.research.sickkids.ca\/tabori\/research\/telomeres-maintenance\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/lab.research.sickkids.ca\/tabori\/research\/telomeres-maintenance\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/lab.research.sickkids.ca\/tabori\/research\/telomeres-maintenance\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\/\/lab.research.sickkids.ca\/tabori\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research\",\"item\":\"https:\/\/lab.research.sickkids.ca\/tabori\/research\/\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Telomere Maintenance\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/lab.research.sickkids.ca\/tabori\/#website\",\"url\":\"https:\/\/lab.research.sickkids.ca\/tabori\/\",\"name\":\"Tabori Lab\",\"description\":\"Uri Tabori&#039;s lab at SickKids Research Institute\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/lab.research.sickkids.ca\/tabori\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"Telomere Maintenance - Tabori Lab","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/lab.research.sickkids.ca\/tabori\/research\/telomeres-maintenance\/","og_locale":"en_US","og_type":"article","og_title":"Telomere Maintenance","og_description":"Telomere Maintenance Telomere maintenance is a hallmark of human cancer. In the majority of human cancer, telomere maintenance is achieved by reactivation of telomerase. TERT \u2013 a reverse transcriptase component of telomerase \u2013 is a proto-oncogene that governs the telomerase activity and is transcriptionally dysregulated in cancer. 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