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Chromatin Mediators of Estrogen Receptor Biology

Objective

Estrogen Receptor (ER) drives proliferation in breast cancers and drugs such as tamoxifen and Aromatase Inhibitors, that target ER activity, are first line treatments in clinical practice. However drug resistance is a significant clinical problem. My laboratory has reported that chromatin-modifying pioneer factors are required for ER to bind the genome, and may constitute a unique opportunity for treating drug resistant cancer. My proposal consists of two complementary approaches to comprehensively explore how Estrogen Receptor interacts with these factors to direct transcription. (1) We will demonstrate that FoxA1 and the Groucho protein TLE1 are critical mediators of ER-chromatin interactions by mapping TLE1 binding sites on a genome-wide basis, and functionally testing the roles these factors play with ER in genomic remodeling, gene transcription, cell proliferation, and endocrine resistance. (2) More globally, to characterise ER transcriptional partners on a molecular basis, we will identify the complete complement of ER-associated proteins using novel proteomic approaches. Taken together, these approaches will explore how ER employs pioneer factors mechanistically, and will identify other potential players.

Field of science

  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /natural sciences/biological sciences/genetics and heredity/genome
  • /medical and health sciences/clinical medicine/oncology/cancer/breast cancer

Call for proposal

ERC-2009-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 731 548,47
Principal investigator
Jason Scott Carroll (Dr.)
Administrative Contact
Renata Schaeffer (Ms.)

Beneficiaries (2)

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 731 548,47
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
Principal investigator
Jason Scott Carroll (Dr.)
Administrative Contact
Renata Schaeffer (Ms.)
CANCER RESEARCH UK LBG
United Kingdom
EU contribution
€ 768 796,53
Address
St John Street 407 Angel Building
EC1V 4AD London
Activity type
Research Organisations
Administrative Contact
Emma Ryley (Dr.)