Wellcome Trust PhD Programme for Clinicians at the University of Cambridge. (360G-Wellcome-103395_Z_13_Z)

£229,922

Two thirds of breast cancer is luminal, driven by oestrogen signalling via overexpressed oestrogen receptor. The pioneer transcription factor FoxA1 is required for transcription of ER target genes driving cell growth in both drug-sensitive and resistant contexts. The aim of the proposed research is to characteriseFoxA1 regulatory factors to provide mechanistic insight into how FoxA1 function could be manipulated for therapeutic advantage in hormone resistant ER+ breastcancer. Specifically, I will develop a high-throughput siRNA screen and test growth of multiple breast cancer cell lines, including paired wild-type and tamoxifen-resistant MCF7 cells, using siRNAs to the human kinome. Chromatin fractionation will be used to determine whether growth modifiers prevent FoxA1and ER from binding to DNA. Any effect on FoxA1 and ER function will be determined using ChIP-seq, RNA-seq and proteomic analysis to explore change in binding profiles, gene expression and protein interactions, respectively.Candidate kinase inhibitors that modify cell growth via regulation of FoxA1 function will then be tested on a validated tumour explant model.

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Grant Details

Amount Awarded 229922
Applicant Surname Johnston
Approval Committee PhD Studentships
Award Date 2013-09-16T00:00:00+00:00
Financial Year 2012/13
Grant Programme: Title PhD Training Fellowship for Clinicians
Internal ID 103395/Z/13/Z
Lead Applicant Dr Simon Johnston
Partnership Value 229922
Planned Dates: End Date 2016-09-30T00:00:00+00:00
Planned Dates: Start Date 2013-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Krishna Chatterjee