Andrea Califano, “Elucidating master integrators of tumor-related phenotypes”

Event Details
  • Date/Time:
    • Tuesday September 21, 2010
      11:00 am - 12:00 pm
  • Location: Klaus Advanced Computing Building (Klaus), Room 1116E
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Contact

Jessica Gilmore Forness
Center Manager
Center for the Study of Systems Biology
Phone: (404) 407-8976
E-mail: jessica.gilmore@biology.gatech.edu
http://cssb.biology.gatech.edu/

Summaries

Summary Sentence: 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.

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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 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  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 “Elucidating master integrators of tumor-related phenotypes".

Abstract: The identification of genes acting synergistically as master regulators of physiologic and pathologic cellular phenotypes is a key open problem in systems biology, Here we use a molecular interaction based approach to identify the repertoire of transcription factors (TFs) of a master regulatory module responsible for synergistic activation of a tumor-specific signature. Specifically, we used the ARACNe algorithm and other computational tools to infer regulatory interactions responsible for initiating and maintaining the mesenchymal phenotype of Glioblastoma Multiforme (GBM), previously associated with the poorest disease prognosis. Expression of mesenchymal genes is a hallmark of aggressiveness but the upstream regulators of the signature are unknown. Starting from the unbiased analysis of all TFs, we identify a highly interconnected module of six TFs jointly regulating >75% of the genes in the signature. Two TFs (Stat3 and C/EBPb), in particular, display features of initiators and master regulators of module activity. Biochemical validation confirms that the TFs in the module bind to the inferred promoters in vivo and ectopic expression of the master TFs activates expression of the mesenchymal signature. These effects are sufficient to trigger mesenchymal transformation of neural stem cells, which become highly tumorigenic in vivo, and promote migration and invasion. Conversely, silencing of Stat3 and C/EBPb in human glioma cells leads to collapse of the mesenchymal signature and reduction of tumor aggressiveness. Our results reveal that activation of a small transcriptional module is necessary and sufficient to induce a mesenchymal phenotype in malignant brain tumors.

Dr. Califano's interests are broadly defined within the field of Systems Biology, with specific application to human malignancies. In particular his lab has spearheaded early efforts to assemble genome-wide, context-specific maps of molecular interactions in human cells, by integrating several reverse engineering approaches. These maps have shown significant promise in the rational elucidation of both physiological and pathological phenotypes. Over the last few years, his lab has assembled biochemically validated, genome-wide map of transcriptional and post-transcriptional interaction in several human cell contexts, including B cell, Breast Carcinoma, Glioma, and normal and tumor-related Stem Cells. These maps are being extensively used for the unbiased dissection of dysregulated pathways in related human malignancies. The Califano lab integrates the development of analytical methodologies with high-throughput experimental assays necessary for data generation and biochemical/biological validation.

CSSB Distinguished Lecture Series: Fall 2010
09/21/2010 - Andrea Califano, Columbia University
10/12/2010 - Bruce Berne, Columbia University
10/26/2010 - Gary Siuzdak, The Scripps Research Institute
11/09/2010 - Charles Cantor, Boston University
11/11/2010 - Kristin Brown, GlaxoSmithKline
11/30/2010 - JoAnne Stubbe, MIT

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Status
  • Created By: Jessica Forness
  • Workflow Status: Published
  • Created On: Aug 30, 2010 - 12:44pm
  • Last Updated: Oct 7, 2016 - 9:52pm