Role of CDCA/PP1 in Triple Negative Breast Cancer (TNBC)

Estrogen, progesterone, and HER2 receptor-negative (triple-negative breast cancers TNBC) encompass the most clinically challenging subtype for which targeted therapeutics are lacking.  To identify critical therapeutic targets, a better understanding of the biology of triple-negative breast cancer is therefore needed.
We have identified a phosphatase complex CDCA2/PP1 that acts as an epigenetic modifier and it is overexpressed in breast cancer cells, more specifically in TNBC, and its overexpression correlates with bad prognosis. Interestingly, depletion of CDCA2 in the TNBC cell lines blocks the ability of these cells to proliferate in wound healing assays suggesting that decreasing CDCA2 level could be an avenue for therapy. However the detailed molecular mechanisms for this are not known.

The project aims to identify the molecular pathways that are controlled by CDCA2 in TNBC and to develop small molecules or cyclic peptides that interfere with the formation or activity of this complex. For this, the student will use biochemical and molecular biology tools to identify the key molecules that are subjected to differential regulation in TNBC cells (Mass spectrometry and Reverse Phase Protein Array) before and after depletion of CDCA2.
In collaboration with Prof Manfred Auer at Edinburgh University, the student will use a phage display library to isolate cyclic peptides that bind specifically to the complex and then will test their efficacy on arresting proliferation of TNBC cells.

How to apply

If you are interested in applying for the above PhD topic please follow the steps below:

1. Contact the supervisor by email or phone to discuss your interest and find out if you would be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
2. Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
3. Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.

Good luck!

This is a self funded topic

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.

Meet the Supervisor(s)

Paola Vagnarelli - Qualifications: - PhD in Genetics and Molecular Biology, University of Pavia, Italy  Degree in Biological Sciences, University of Pavia, Italy Professional experience - 1993-1996  Postdoctoral Research Fellow, Dipartimento di Genetica e Microbiologia Universita’ di Pavia 1997    Visiting Scientist MRC Human Genetics Unit, Edinburgh 1998- 2012 Postdoctoral Research Fellow Wellcome Trust Centre for Cell Biology Edinburgh (Prof WC Earnshaw) 2102    Lecturer School of Health Sciences and Social Care, Department of Biosciences, Brunel University London