Seminars – Large audience – From Genomics to Medicine: Uncovering and targeting the genetic circuits underlying GWAS and cancer

@manoliskellis will talk @institut_curie, 08-31-2015 at 11AM, about Uncovering and targeting the genetic circuits underlying GWAS and cancer

Upcoming Events : C3BI Seminars – Large audience – 08/31/2015 at 11:00 am in

Date : 08/31/2015 at 11:00 am Location : Institut Curie, Centre de Recherche – Paris – Amphithéâtre Biologie du développement et cancer Speakers/Trainers : Manolis Kellis, Professor , MIT Computer Science and Artificial Intelligence Lab from Broad Institute of MIT and Harvard For any questions, suggestions (or to volunteer) for future talks/trainings or general feedback please contact us at  c3bi-ask@pasteur.fr

From Genomics to Medicine: Uncovering and targeting the genetic circuits underlying GWAS and cancer

Perhaps the greatest surprise of genome-wide association studies (GWAS) of human disease is that 90% of top-scoring disease-associated loci lie outside protein-coding regions. This has increased the urgency of mapping non-coding DNA elements and regulatory circuits, in order to understand the molecular basis of human disease. To address this challenge, we have developed and applying new methods to systematically characterize the epigenomic landscape of diverse primary human cells and tissues, resulting in the annotation of 2.3M enhancer elements across 127 primary human tissues and cell types. We also predicted tissue-specific regulatory networks linking these enhancers to their upstream regulators and target genes, and enable us to weave genetic information from GWAS through these networks to recognize preferentially-disrupted genes, regulators, and biological processes. In this talk, I will describe the use of non-coding annotations and circuits for understanding the molecular basis of genetic differences underlying common disease and cancer: (1) We uncover the mechanistic basis of GWAS hits, predicting and experimentally validating the causal variants, cell types of action, upstream regulators, downstream genes, and their molecular, cellular and organismal phenotypes in the context of obesity. (2) We combine genetic and epigenomic evidence to prioritize and experimentally validate weakly-associated variants in the context of cardiac repolarization phenotypes, showing that epigenomic data enables robust discovery with much smaller cohorts. (3) We use our regulatory predictions to identify new cancer genes based on recurrent somatic mutations in their linked upstream regulatory elements, revealing out-of-context de-repression as a common cancer strategy in the context of prostate cancer. These three applications, spanning the spectrum of common, rare, and somatic variants, illustrate the power and broad applicability of epigenomic annotations and regulatory networks for understanding human disease and cancer. More Manolis Kellis is a Professor of Computer Science at MIT, where he directs the MIT Computational Biology Group (compbio.mit.edu). He has helped direct several large-scale genomics projects, including the NIH Roadmap Epigenomics project, the comparative analysis of 29 mammals, the Encyclopedia of DNA Elements (ENCODE) project, and the Genotype Tissue-Expression (GTEx) project. He received the US Presidential Early Career Award in Science and Engineering (PECASE), the NSF CAREER award, the Alfred P. Sloan Fellowship. He obtained his Ph.D. from MIT, where he received the Sprowls award for the best doctorate thesis in computer science. He lived in Greece and France before moving to the US.

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C3BI Meeting – Seminar – Large audience – Combating cancer: from magic bullets to synthetic interactions and signaling network modeling

From magic bullets to synthetic interactions & signaling network modeling talk by Emmanuel Barillot @institut_curie #cancer #C3BIPasteur

Upcoming Events : Seminar – Large audience 06/04/2015 at 02:00 pm at François Jacob Amphitheatre in the François Jacob building (BIME – 26)

Date : 06/04/2015 at 02:00 pm Location : François Jacob Amphitheatre in the François Jacob building (BIME – 26) Speakers : Emmanuel Barillot, Head of Department of Computational Systems Biology of Cancer at Institut Curie, U900 INSERM, Mines ParisTech. For any questions, suggestions (or to volunteer) for future talks or general feedback please contact us at bioinfo-hub@pasteur.fr

Combating cancer: from magic bullets to synthetic interactions and signaling network modeling

Four decades of cancer molecular biology research have led to the identification of many molecular determinants of this pathology, and resulted in significant progress in medical treatment. First concepts like magic bullets and oncogene addictions were introduced with the idea that one single gene might have causal role in cancer, or that a strategy of treatment could be focused on one supposedly single gene fragility point. Though it bore fruits in biology and in clinics, this reasoning has shown its limitations when it appeared that the molecular pathways governing tumorigenesis and tumor progression are tightly interconnected in a complex network of interactions which covers essential cell processes named hallmarks of cancer (DNA repair, proliferation, death, differentiation, immune response…), and whose crosstalks, feedbacks and compensatory mechanisms invalidated the former simplistic reasoning and on the clinical side provided a profusion of tumor escape paths to existing treatments. The concept of synthetic pairwise interactions between genes that jointly control phenotypes was then introduced, and shed light on cancer biology as well as it opened perspectives of new therapeutic strategies, that exploits the availability of a growing list of targeted inhibitors which are able to inactivate specifically one given protein. The principle of synthetic pairwise interaction is very fruitful, but also shows limits, and it appears today that the modeling of tumor signaling network is required to explore these interactions, explain the biology of cancer, and design innovative treatment strategies. The talk will present several steps in this direction. Please join us and share your experience, views and thoughts on the talk. We want this meeting to have an interactive and lively atmosphere with many debates.

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