Systems Biology<\/li>\n<\/ul>\nResearch description<\/h2>\n
The Harrington laboratory has employed several model organisms to dissect the dosage-sensitive regulation of telomere homeostasis and its consequences in aging, cancer, and disease. In the single-celled genetic model S. cerevisiae<\/em> (baker\u2019s yeast), her group conducted genome-wide genetic screens to identify genes whose absence affects survival when telomerase expression is reduced or abrogated. These screens identified a pathway for cell survival that acts independently of telomerase and homologous recombination (LeBel et al., Genetics 2009).<\/p>\nUsing mammalian genetic models, Dr. Harrington and her group carried out a long-term analysis of telomere dynamics and stem cell function in cells that possess only half the normal dosage of the telomerase reverse transcriptase, TERT. In this setting, telomeres erode gradually with time but do not become critically short and stem cell function is preserved (Meznikova et al., Dis Models Mech 2009). The outcome of telomere erosion, however, is context-dependent and dosage-dependent. A partial reduction in TERT dosage leads to a dramatic loss in stem cell function in when telomeres begin at a shorter length (Strong et al., Mol Cell Biol 2010), or when telomerase is absent altogether (Meznikova et al., Dis Models Mech 2009; Erdmann et al., Proc Natl Acad Sci USA 2004).<\/p>\n
In human cell models, the Harrington laboratory identified regions of TERT necessary to avoid or escape cellular senescence and to interact with other telomerase accessory factors (Sealey et al., Nucl Acids Res 2010; Ibid, BMC Mol Biol 2011). A novel human tumor model was also developed in which TERT expression is genetically controlled. This new model establishes that human tumor formation does not depend on telomerase or other means of telomere maintenance while telomeres remain at a functional length (Taboski et al., Cell Reports, 2012). However, once telomeres erode to a critical length, the tumor cells lose viability and cannot escape via activation of telomerase or other mechanisms of telomere maintenance. This discovery suggests that telomerase inhibition in tumors with longer telomeres would induce a delayed but potentially effective tumor regression.<\/p>\n
The future direction of Dr. Harrington\u2019s research at IRIC is to use these human tumor models to identify pathways whose inhibition increases the susceptibility of cancer cells to telomere damage and cell death, or whose enhancement might improve cell viability in contexts where telomerase function is limiting as in aging or in certain degenerative diseases.<\/p>\n<\/div>\n\n
Publications<\/h3>\n\n- Taboski MAS, Sealey DCF, Dorrens J, Tayade C, Betts DH, Harrington L<\/strong> (2012) Long telomeres bypass the requirement for telomere length maintenance in human tumorigenesis. Cell Reports, online release February 2nd<\/sup>.<\/li>\n
- \u00a0Gardano L, Holland L, Oulton R, Le Bihan T, Harrington<\/strong> L<\/strong> (2011) Native gel electrophoresis of human telomerase<\/strong> distinguishes active complexes with or without dyskerin. Nucleic Acids Res. 2011 e-pub ahead of print, Dec 19.<\/li>\n
- \u00a0Sealey DC, Kostic AD, Lebel C, Pryde F, Harrington L<\/strong> (2011) The TPR-containing domain within Est1 homologs exhibits species-specific roles in telomerase<\/strong> interaction and telomere<\/strong> length homeostasis. BMC Mol Biol. 12:45.<\/li>\n
- \u00a0Reynolds GE, Gao Q, Miller D, Snow BE, Harrington LA, Murnane JP. (2011) PIF1 disruption or NBS1 hypomorphism does not affect chromosome healing or fusion resulting from double-strand breaks near telomeres<\/strong> in murine embryonic stem cells. DNA Repair 10:1164.<\/li>\n
- \u00a0Rashid-Kolvear F, Taboski MA, Nguyen J, Wang DY, Harrington LA, Done SJ. (2010) Troglitazone suppresses telomerase<\/strong> activity independently of PPARgamma in estrogen-receptor negative breast cancer cells. BMC Cancer 10:390.<\/li>\n<\/ul>\n
<\/p>\n
<\/p>\n","protected":false},"excerpt":{"rendered":"
Coordonn\u00e9es IRIC – Universit\u00e9 de Montr\u00e9al T 514 343-6729 lea.harrington@umontreal.ca Publications Taboski MAS, Sealey DCF, Dorrens J, Tayade C, Betts DH, Harrington L (2012) Long telomeres bypass the requirement for […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":3557,"menu_order":0,"comment_status":"closed","ping_status":"open","template":"","meta":{"footnotes":""},"class_list":["post-3621","page","type-page","status-publish","hentry"],"yoast_head":"\n
Harrington, Lea, Ph.D. - Programmes de biologie mol\u00e9culaire<\/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:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Harrington, Lea, Ph.D. - Programmes de biologie mol\u00e9culaire\" \/>\n<meta property=\"og:description\" content=\"Coordonn\u00e9es IRIC – Universit\u00e9 de Montr\u00e9al T 514 343-6729 lea.harrington@umontreal.ca Publications Taboski MAS, Sealey DCF, Dorrens J, Tayade C, Betts DH, Harrington L (2012) Long telomeres bypass the requirement for […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/\" \/>\n<meta property=\"og:site_name\" content=\"Programmes de biologie mol\u00e9culaire\" \/>\n<meta property=\"article:modified_time\" content=\"2013-08-16T19:55:08+00:00\" \/>\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=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/\",\"url\":\"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/\",\"name\":\"Harrington, Lea, Ph.D. - Programmes de biologie mol\u00e9culaire\",\"isPartOf\":{\"@id\":\"https:\/\/biomol.umontreal.ca\/#website\"},\"datePublished\":\"2012-03-13T13:23:14+00:00\",\"dateModified\":\"2013-08-16T19:55:08+00:00\",\"breadcrumb\":{\"@id\":\"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Accueil\",\"item\":\"https:\/\/biomol.umontreal.ca\/en\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research\",\"item\":\"https:\/\/biomol.umontreal.ca\/en\/research\/\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Our professors\",\"item\":\"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Harrington, Lea, Ph.D.\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/biomol.umontreal.ca\/#website\",\"url\":\"https:\/\/biomol.umontreal.ca\/\",\"name\":\"Programmes de biologie mol\u00e9culaire\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/biomol.umontreal.ca\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Harrington, Lea, Ph.D. - Programmes de biologie mol\u00e9culaire","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:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/","og_locale":"en_US","og_type":"article","og_title":"Harrington, Lea, Ph.D. - Programmes de biologie mol\u00e9culaire","og_description":"Coordonn\u00e9es IRIC – Universit\u00e9 de Montr\u00e9al T 514 343-6729 lea.harrington@umontreal.ca Publications Taboski MAS, Sealey DCF, Dorrens J, Tayade C, Betts DH, Harrington L (2012) Long telomeres bypass the requirement for […]","og_url":"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/","og_site_name":"Programmes de biologie mol\u00e9culaire","article_modified_time":"2013-08-16T19:55:08+00:00","twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/","url":"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/","name":"Harrington, Lea, Ph.D. - Programmes de biologie mol\u00e9culaire","isPartOf":{"@id":"https:\/\/biomol.umontreal.ca\/#website"},"datePublished":"2012-03-13T13:23:14+00:00","dateModified":"2013-08-16T19:55:08+00:00","breadcrumb":{"@id":"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/harrington-lea-ph-d\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Accueil","item":"https:\/\/biomol.umontreal.ca\/en\/"},{"@type":"ListItem","position":2,"name":"Research","item":"https:\/\/biomol.umontreal.ca\/en\/research\/"},{"@type":"ListItem","position":3,"name":"Our professors","item":"https:\/\/biomol.umontreal.ca\/en\/research\/les-professeurs\/"},{"@type":"ListItem","position":4,"name":"Harrington, Lea, Ph.D."}]},{"@type":"WebSite","@id":"https:\/\/biomol.umontreal.ca\/#website","url":"https:\/\/biomol.umontreal.ca\/","name":"Programmes de biologie mol\u00e9culaire","description":"","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/biomol.umontreal.ca\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"}]}},"_links":{"self":[{"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/pages\/3621","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/comments?post=3621"}],"version-history":[{"count":1,"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/pages\/3621\/revisions"}],"predecessor-version":[{"id":3624,"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/pages\/3621\/revisions\/3624"}],"up":[{"embeddable":true,"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/pages\/3557"}],"wp:attachment":[{"href":"https:\/\/biomol.umontreal.ca\/en\/wp-json\/wp\/v2\/media?parent=3621"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}