{"60699":{"#nid":"60699","#data":{"type":"event","title":"Andrea Califano, \u201cElucidating master integrators of tumor-related phenotypes\u201d","body":[{"value":"\u003Cp\u003EDr. Jeffrey Skolnick and the Center for the Study of Systems Biology are pleased to host Distinguished Lecture Series in Systems Biology Speaker Dr. Andrea Califano who is a Professor in Biomedical Informatics at Columbia University, Chief of the Division of Biomedical Informatics, Director of the Columbia Initiative in Systems Biology, Director of Center for the Multiscale Analysis of Genetic Networks and Associate Director for Bioinformatics in the\u0026nbsp; Irving Cancer Research Center. His seminar will be held on Tuesday, September 14, 2010 from 11:00 AM to 12:00 PM in the Klaus Advanced Computing Building (Klaus), Room 1116E. The title of his talk will be \u201c\u003Cstrong\u003EElucidating master\nintegrators of tumor-related phenotypes\u0022.\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EAbstract: \u003C\/strong\u003EThe identification of genes\nacting synergistically as master regulators of physiologic and pathologic\ncellular phenotypes is a key open problem in systems biology, Here we use a\nmolecular interaction based approach to identify the repertoire of transcription\nfactors (TFs) of a master regulatory module responsible for synergistic\nactivation of a tumor-specific signature. Specifically, we used the ARACNe\nalgorithm and other computational tools to infer regulatory interactions\nresponsible for initiating and maintaining the mesenchymal phenotype of\nGlioblastoma Multiforme (GBM), previously associated with the poorest disease\nprognosis. Expression of mesenchymal genes is a hallmark of aggressiveness but\nthe upstream regulators of the signature are unknown. Starting from the\nunbiased analysis of all TFs, we identify a highly interconnected module of six\nTFs jointly regulating \u0026gt;75% of the genes in the signature. Two TFs (Stat3\nand C\/EBPb), in particular, display features of initiators and master regulators\nof module activity. Biochemical validation confirms that the TFs in the module\nbind to the inferred promoters in vivo and ectopic expression of the master TFs\nactivates expression of the mesenchymal signature. These effects are sufficient\nto trigger mesenchymal transformation of neural stem cells, which become highly\ntumorigenic in vivo, and promote migration and invasion. Conversely, silencing\nof Stat3 and C\/EBPb in human glioma cells leads to collapse of the mesenchymal\nsignature and reduction of tumor aggressiveness. Our results reveal that\nactivation of a small transcriptional module is necessary and sufficient to\ninduce a mesenchymal phenotype in malignant brain tumors.\u003C\/p\u003E\u003Cp\u003EDr. Califano\u0027s interests are broadly defined within the field of Systems\n Biology, with specific application to human malignancies. In particular\n his lab has spearheaded early efforts to assemble genome-wide, \ncontext-specific maps of molecular interactions in human cells, by \nintegrating several reverse engineering approaches. These maps have \nshown significant promise in the rational elucidation of both \nphysiological and pathological phenotypes. Over the last few years, his \nlab has assembled biochemically validated, genome-wide map of \ntranscriptional and post-transcriptional interaction in several human \ncell contexts, including B cell, Breast Carcinoma, Glioma, and normal \nand tumor-related Stem Cells. These maps are being extensively used for \nthe unbiased dissection of dysregulated pathways in related human \nmalignancies. The Califano lab integrates the development of analytical \nmethodologies with high-throughput experimental assays necessary for \ndata generation and biochemical\/biological validation.\u003C\/p\u003E\n\n\u003Cp\u003ECSSB Distinguished Lecture Series: Fall 2010\u003Cbr \/\u003E09\/21\/2010\n - Andrea Califano, Columbia University\u003Cbr \/\u003E10\/12\/2010 - Bruce Berne, \nColumbia University\u003Cbr \/\u003E10\/26\/2010 - Gary Siuzdak, The Scripps Research \nInstitute\u003Cbr \/\u003E11\/09\/2010 - Charles Cantor, Boston University\u003Cbr \/\u003E11\/11\/2010\n - Kristin Brown, GlaxoSmithKline\u003Cbr \/\u003E11\/30\/2010 - JoAnne Stubbe, MIT\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Dr. Jeffrey Skolnick and the Center for the Study of Systems Biology are pleased to host Distinguished Lecture Series in Systems Biology speaker Dr. Andrea Califano from Columbia University."}],"uid":"27199","created_gmt":"2010-08-30 16:44:36","changed_gmt":"2016-10-08 01:52:11","author":"Jessica Forness","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2010-09-21T12:00:00-04:00","event_time_end":"2010-09-21T13:00:00-04:00","event_time_end_last":"2010-09-21T13:00:00-04:00","gmt_time_start":"2010-09-21 16:00:00","gmt_time_end":"2010-09-21 17:00:00","gmt_time_end_last":"2010-09-21 17:00:00","rrule":null,"timezone":"America\/New_York"},"extras":["free_food"],"related_links":[{"url":"http:\/\/vesta.cumc.columbia.edu\/dbmi\/facdb\/profile\/profile.php?id=anc9048","title":"Faculty Website"},{"url":"http:\/\/wiki.c2b2.columbia.edu\/califanolab\/index.php\/Main_Page","title":"Lab Wsbsite"},{"url":"http:\/\/www.c2b2.columbia.edu\/page.php?pageid=22","title":"Center for Computational Biology and Bioinformatics (C2B2)"},{"url":"http:\/\/magnet.c2b2.columbia.edu\/","title":"Multiscale Analysis of Genomic and Cellular Networks (MAGNet)"},{"url":"http:\/\/hiccc.columbia.edu\/","title":"Herbert Irving Comprehensive Cancer Center"}],"groups":[{"id":"1182","name":"General"},{"id":"1275","name":"School of Biological Sciences"},{"id":"1278","name":"College of Sciences"}],"categories":[],"keywords":[],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EJessica Gilmore Forness\u003Cbr \/\u003ECenter Manager\u003Cbr \/\u003ECenter for the Study of \nSystems Biology\u003Cbr \/\u003EPhone: (404) 407-8976 \u003Cbr \/\u003EE-mail: \n\u003Ca href=\u0022mailto:jessica.gilmore@biology.gatech.edu\u0022\u003Ejessica.gilmore@biology.gatech.edu\u003C\/a\u003E\u003Cbr \/\u003E\u003Ca href=\u0022http:\/\/cssb.biology.gatech.edu\/\u0022 title=\u0022http:\/\/cssb.biology.gatech.edu\/\u0022\u003Ehttp:\/\/cssb.biology.gatech.edu\/\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}