Opendata, web and dolomites

METCLL SIGNED

Discovery and validation of ‘epidrivers’ of cancer evolution and resistance to therapy

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

 METCLL project word cloud

Explore the words cloud of the METCLL project. It provides you a very rough idea of what is the project "METCLL" about.

genetic    investigation    cohort    leukemia    form    complementary    al    amenable    fueled    tumoral    cll    robustly    shown    exploring    pathogenesis    complexity    tumour    aberrant    therapy    selective    sequencing    pursue    building    epigenome    epigenetic    modify    creates    pressures    epidrivers    acquisition    screen    encoded    somatic    escape    search    natural    genetically    trajectories    sub    candidate    bulk    source    cell    chronic    et    relapse    disease    tumor    period    editing    dysregulates    cancers    modifications    population    curie    variation    uncovered    fuelling    first    amount    solid    heterogeneity    superior    aggressive    cancer    extend    investigations    methylation    alterations    intra    validated    subject    shapes    ngs    technological    reconstruction    capacity    lymphocytic    enhances    linked    data    evolutionary    cells    paradigm    dna    single    understand    heritable    genes    returning    positively    undergo    generation    integrative    outgoing    evolution    breast    plasticity    independent    epigenetics    landau    stochastic   

Project "METCLL" data sheet

The following table provides information about the project.

Coordinator
INSTITUT CURIE 

Organization address
address: rue d'Ulm 26
city: PARIS
postcode: 75231
website: www.curie.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 264˙668 €
 EC max contribution 264˙668 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-GF
 Starting year 2018
 Duration (year-month-day) from 2018-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT CURIE FR (PARIS) coordinator 264˙668.00
2    CORNELL UNIVERSITY US (ITHACA NY) partner 0.00

Map

 Project objective

Intra-tumoral heterogeneity allows all form of cancers to undergo an evolutionary process in response to selective pressures, such as therapy, which results in a more aggressive disease. As chronic lymphocytic leukemia (CLL) are particularly amenable to evolutionary investigations, it has been shown that CLL’s capacity to escape therapy is linked in to genetic evolution, which is fueled by intra-tumoral heterogeneity. Aberrant DNA methylation can also dysregulates genes involved in CLL pathogenesis. Like genetic alterations, DNA methylation modifications are heritable and subject to natural selection. Landau et al have studied sub-population DNA methylation heterogeneity in CLL and uncovered a large amount of stochastic variation. The acquisition of stochastic DNA methylation alterations enhances epigenetic plasticity and creates a non–genetically encoded source of heterogeneity, fuelling tumour cells in their search for superior evolutionary trajectories. These new data modify the way we understand cancer epigenetics, and offer a new field of investigation: identify “epidrivers”, i.e. somatic epigenetic alterations leading to cancer-heterogeneity and which are positively selected through cancer evolution. Thus, I will pursue in this project four independent yet complementary aims. During my outgoing period I will robustly identify epidrivers from bulk next-generation sequencing (NGS) (Aim 1) and from single-cell NGS (Aim 2) of a large CLL cohort. Candidate epidrivers uncovered from the first two aims, will be further validated in a large-scale epigenome editing screen (Aim 3). Then building upon technological development from Aim 2 and 3, during my returning period at Curie Institute, I will extend this important paradigm to solid tumor by exploring breast cancer evolution (Aim 4). This integrative analysis of epigenetic heterogeneity will enable the reconstruction of tumor epigenetic population complexity and how it shapes disease relapse and evolution.

 Publications

year authors and title journal last update
List of publications.
2019 Anna S. Nam, Kyu-Tae Kim, Ronan Chaligne, Franco Izzo, Chelston Ang, Justin Taylor, Robert M. Myers, Ghaith Abu-Zeinah, Ryan Brand, Nathaniel D. Omans, Alicia Alonso, Caroline Sheridan, Marisa Mariani, Xiaoguang Dai, Eoghan Harrington, Alessandro Pastore, Juan R. Cubillos-Ruiz, Wayne Tam, Ronald Hoffman, Raul Rabadan, Joseph M. Scandura, Omar Abdel-Wahab, Peter Smibert, Dan A. Landau
Somatic mutations and cell identity linked by Genotyping of Transcriptomes
published pages: 355-360, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1367-0
Nature 571/7765 2020-01-21
2019 Federico Gaiti, Ronan Chaligne, Hongcang Gu, Ryan M. Brand, Steven Kothen-Hill, Rafael C. Schulman, Kirill Grigorev, Davide Risso, Kyu-Tae Kim, Alessandro Pastore, Kevin Y. Huang, Alicia Alonso, Caroline Sheridan, Nathaniel D. Omans, Evan Biederstedt, Kendell Clement, Lili Wang, Joshua A. Felsenfeld, Erica B. Bhavsar, Martin J. Aryee, John N. Allan, Richard Furman, Andreas Gnirke, Catherine J. Wu, Alexander Meissner, Dan A. Landau
Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia
published pages: , ISSN: 0028-0836, DOI: 10.1038/s41586-019-1198-z
Nature 2020-01-21
2019 Alessandro Pastore, Federico Gaiti, Sydney X. Lu, Ryan M. Brand, Scott Kulm, Ronan Chaligne, Hongcang Gu, Kevin Y. Huang, Elena K. Stamenova, Wendy Béguelin, Yanwen Jiang, Rafael C. Schulman, Kyu-Tae Kim, Alicia Alonso, John N. Allan, Richard R. Furman, Andreas Gnirke, Catherine J. Wu, Ari M. Melnick, Alexander Meissner, Bradley E. Bernstein, Omar Abdel-Wahab, Dan A. Landau
Corrupted coordination of epigenetic modifications leads to diverging chromatin states and transcriptional heterogeneity in CLL
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-09645-5
Nature Communications 10/1 2020-01-21
2019 Ronan Chaligne, Anna S. Nam, Dan A. Landau
TARGET-seq Takes Aim at Cancer Evolution through Multi-omics Single-Cell Genotyping and Transcriptomics
published pages: 1092-1094, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.03.009
Molecular Cell 73/6 2020-01-21

Are you the coordinator (or a participant) of this project? Plaese send me more information about the "METCLL" project.

For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.

Send me an  email (fabio@fabiodisconzi.com) and I put them in your project's page as son as possible.

Thanks. And then put a link of this page into your project's website.

The information about "METCLL" are provided by the European Opendata Portal: CORDIS opendata.

More projects from the same programme (H2020-EU.1.3.2.)

TheaTheor (2018)

Theorizing the Production of 'Comedia Nueva': The Process of Play Configuration in Spanish Golden Age Theater

Read More  

IRF4 Degradation (2019)

Using a novel protein degradation approach to uncover IRF4-regulated genes in plasma cells

Read More  

KiT-FIG (2019)

Kidney Transplantation - Functional ImmunoGenomics

Read More