{"id":4844,"date":"2014-06-03T10:24:45","date_gmt":"2014-06-03T14:24:45","guid":{"rendered":"https:\/\/web.uri.edu\/inbre\/?page_id=4844"},"modified":"2014-06-03T10:24:45","modified_gmt":"2014-06-03T14:24:45","slug":"tipping","status":"publish","type":"page","link":"https:\/\/web.uri.edu\/riinbre\/research\/ecd\/tipping\/","title":{"rendered":"Proteomic and metabolic analysis of IDH mutant gliomas in Drosophila melanogaster"},"content":{"rendered":"<p><strong>Investigator:<\/strong> Marla Tipping, Providence College<\/p>\n<p><strong>Mentor:<\/strong> Kristi Wharton, Brown University<\/p>\n<p><strong>Scientific Theme:<\/strong> Cancer<\/p>\n<p style=\"text-align: justify\"><strong>Abstract:\u00a0<\/strong>Gliomas are the most common and fatal form of brain cancer. In an effort to better understand the biology\u00a0of these rapidly proliferating, and aggressively invasive tumors, Drosophila researchers have attempted\u00a0to reproduce the human glioma phenotype in the fruit fly. One group was able to successfully generate\u00a0gliomas by enhancing the activity of a known oncogene, Epidermal Growth Factor Receptor (EGFR),\u00a0implicated in glioblastoma formation. This result suggests that the process of glial cell tumorigenesis is\u00a0likely conserved in the fly, and presents the fly as a promising model for the study of these tumors.\u00a0Recently genes encoding the metabolic enzymes Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) were\u00a0found to be mutated in up to 70% of low-grade and medium grade gliomas, and in 15-20% of adult acute\u00a0leukemia samples. These findings were the first to link the IDH gene to tumorigenesis. IDH1 and IDH2\u00a0function to irreversibly catalyze the oxidative decarboxylation of isocitrate to \u03b1-ketoglutarate (\u03b1-KG).\u00a0Although these are important metabolic enzymes, little is known about the metabolic impact on cells\u00a0harboring mutant IDH proteins. This proposal aims to model the IDH mutant phenotype in Drosophila glial\u00a0cells with the goal to characterize their metabolic status, and elucidate changes in IDH enzymatic activity\u00a0and protein interaction network. These aims will be achieved by 1) careful analysis of altered proliferation\u00a0and cellular metabolism in Drosophila Idh1 mutant glia, and 2) investigation of Idh1 protein function via\u00a0identifying proteins interacting with Idh1 mutants, as well as analysis of Idh1 mutant enzymatic activity.\u00a0Results of this study will reveal novel targets for treatment and enhance our ability to treat these\u00a0aggressive tumors at the level of cellular metabolism.<\/p>\n<p style=\"text-align: justify\"><strong>Human Health Relevance:\u00a0<\/strong>Modeling the Isocitrate dehydrogenase (IDH) mutant phenotype in Drosophila will allow for more\u00a0extensive genetic and molecular study of IDH derived gliomas. The investigation of both IDH mutant\u00a0enzyme activity, interactions, and metabolic status will identify potential new targets for the treatment of\u00a0these aggressive tumors.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigator: Marla Tipping, Providence College Mentor: Kristi Wharton, Brown University Scientific Theme: Cancer Abstract:\u00a0Gliomas are the most common and fatal form of brain cancer. In an effort to better understand the biology\u00a0of these rapidly proliferating, and aggressively invasive tumors, Drosophila researchers have attempted\u00a0to reproduce the human glioma phenotype in the fruit fly. One group was [&hellip;]<\/p>\n","protected":false},"author":1036,"featured_media":0,"parent":10203,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-twocol.php","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-4844","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4844","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/users\/1036"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/comments?post=4844"}],"version-history":[{"count":0,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4844\/revisions"}],"up":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/10203"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/media?parent=4844"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}