Opendata, web and dolomites

ER_disease SIGNED

Defining hormonal cross-talk and the role of mutations in estrogen receptor positive breast cancer

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

Project "ER_disease" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

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 United Kingdom [UK]
 Total cost 1˙987˙273 €
 EC max contribution 1˙987˙273 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 1˙987˙273.00

Map

 Project objective

Estrogen Receptor (ER) is the driving transcription factor in ~75% of all breast cancers. ER antagonists are routinely used for treatment, but significant variability exists in clinical response. We are interested in explaining this heterogeneity and exploiting the mechanistic insight. We have recently identified important, but previously uncharacterised cross-talk between ER and the progesterone receptor (PR) and androgen receptor (AR) pathways, both of which are commonly expressed in ER tumours. Recently, ER has been shown to be mutated in ~18-55% of metastatic breast cancers. In addition, two key ER-chromatin regulatory proteins, FoxA1 and GATA3, are mutated in primary ER disease. Finally we have discovered three previously unknown phosphorylation events on FoxA1.

Aim 1: We will comprehensively explore the cross-talk that exists between ER and PR and AR pathways to determine the physiological effects on ER function. Aim 2: We will recapitulate the key mutations observed in ER, FoxA1 and GATA3, to assess the impact on ER-DNA interactions, ER transcriptional activity and cell growth and drug response. This will be explored under different hormonal contexts to identify how the mutational spectrum influences the cross-talk between ER and the parallel PR and AR pathways. Aim 3: We will identify upstream kinase pathways that influence FoxA1 and GATA3 function. Aim 4: We will establish a novel single locus chromatin purification method for isolation of specific chromatin loci, followed by Mass Spectrometry to characterise the potential role of PR and AR variants and to identify unknown regulatory factors.

Given recent biological discoveries and technological advances, we are perfectly positioned to apply cutting-edge tools to glean mechanistic insight into the factors that determine variability within ER disease. This proposal aims to advance our understanding of ER tumour heterogeneity, revealing ways of exploiting this in a clinically meaningful manner.

 Publications

year authors and title journal last update
List of publications.
2020 Sankari Nagarajan, Shalini V. Rao, Joseph Sutton, Danya Cheeseman, Shanade Dunn, Evangelia K. Papachristou, Jose-Enrique Gonzalez Prada, Dominique-Laurent Couturier, Sanjeev Kumar, Kamal Kishore, Chandra Sekhar Reddy Chilamakuri, Silvia-Elena Glont, Emily Archer Goode, Cara Brodie, Naomi Guppy, Rachael Natrajan, Alejandra Bruna, Carlos Caldas, Alasdair Russell, Rasmus Siersbæk, Kosuke Yusa, Igor
ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response
published pages: , ISSN: 1061-4036, DOI: 10.1038/s41588-019-0541-5
Nature Genetics 2020-02-04
2019 Silvia-E. Glont, Igor Chernukhin, Jason S. Carroll
Comprehensive Genomic Analysis Reveals that the Pioneering Function of FOXA1 Is Independent of Hormonal Signaling
published pages: 2558-2565.e3, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.02.036
Cell Reports 26/10 2020-02-04
2018 A. A. Serandour, H. Mohammed, A. Miremadi, K. W. Mulder, J. S. Carroll
TRPS1 regulates oestrogen receptor binding and histone acetylation at enhancers
published pages: , ISSN: 0950-9232, DOI: 10.1038/s41388-018-0312-2
Oncogene 2020-01-21
2016 Jason S. Carroll, Theresa E. Hickey, Gerard A. Tarulli, Michael Williams, Wayne D. Tilley
Deciphering the divergent roles of progestogens in breast cancer
published pages: 54-64, ISSN: 1474-175X, DOI: 10.1038/nrc.2016.116
Nature Reviews Cancer 17/1 2020-01-21
2018 Evangelia K. Papachristou, Kamal Kishore, Andrew N. Holding, Kate Harvey, Theodoros I. Roumeliotis, Chandra Sekhar Reddy Chilamakuri, Soleilmane Omarjee, Kee Ming Chia, Alex Swarbrick, Elgene Lim, Florian Markowetz, Matthew Eldridge, Rasmus Siersbaek, Clive S. D’Santos, Jason S. Carroll
A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-04619-5
Nature Communications 9/1 2020-01-21
2016 Kamila M. Jozwik, Igor Chernukhin, Aurelien A. Serandour, Sankari Nagarajan, Jason S. Carroll
FOXA1 Directs H3K4 Monomethylation at Enhancers via Recruitment of the Methyltransferase MLL3
published pages: 2715-2723, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.11.028
Cell Reports 17/10 2020-01-21
2017 Adam W. Nelson, Arnoud J. Groen, Jodi L. Miller, Anne Y. Warren, Kelly A. Holmes, Gerard A. Tarulli, Wayne D. Tilley, Benita S. Katzenellenbogen, John R. Hawse, Vincent J. Gnanapragasam, Jason S. Carroll
Comprehensive assessment of estrogen receptor beta antibodies in cancer cell line models and tissue reveals critical limitations in reagent specificity
published pages: 138-150, ISSN: 0303-7207, DOI: 10.1016/j.mce.2016.11.016
Molecular and Cellular Endocrinology 440 2020-01-21

Are you the coordinator (or a participant) of this project? Plaese send me more information about the "ER_DISEASE" 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 "ER_DISEASE" are provided by the European Opendata Portal: CORDIS opendata.

More projects from the same programme (H2020-EU.1.1.)

ZARAH (2020)

Women’s labour activism in Eastern Europe and transnationally, from the age of empires to the late 20th century

Read More  

SWIP (2019)

Extended short-wave infrared pulsed fibre laser

Read More  

ChaperoneRegulome (2020)

ChaperoneRegulome: Understanding cell-type-specificity of chaperone regulation

Read More