Developing RAC1B-targeting therapies to improve the treatment outcomes for breast cancer

In this project, transgenic reporter cell lines, which will be generated using CRISPR-mediated gene editing, will be used to screen large drug libraries along with functional assays to analyse breast cancer stem cells and to determine RAC1B activities, cytotoxicity and therapy response when combined with distinct sets of chemotherapeutical agents or targeted treatment modalities.

Those drugs that will be determined to improve the therapy response in vitro by altering RAC1B function will then be tested using transgenic animal models of breast cancer that are available in our research group. These will provide us with the preclinical data demonstrating which RAC1B-interrupting drugs can be safely used in combination with currently available standard-of-care treatments for patients with breast cancer.

• Chen F. et al. RAC1B function is essential for breast cancer stem cell maintenance and chemoresistance of breast tumor cells. Oncogene 42, 679–692 (2023).

Supervisor profile

The overall research direction of our group is to elucidate the mechanisms of breast tumorigenesis during its earliest pre-malignant stages, its progression to metastatic disease, and therapy response of breast tumours, with a particular focus on breast cancer stem cells. With a translational approach we then aim to develop novel preventive and curative treatments that can be used in clinics to improve the treatment outcomes for patients with breast cancer.

In relation to this PhD project, which is a continuation of our recent work (Chen F.et. al), we aim to develop novel therapeutic approaches targeting RAC1B, an alternatively spliced variant of the small GTPase RAC1, to improve the outcome of the chemotherapy and targeted therapy treatments currently used as standard-of care for patients with breast cancer and to provide pre-clinical data for those developed novel therapeutical approaches.

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)

Ahmet Ucar - I am a senior lecturer in toxicology at the Brunel University London and an honorary research fellow at the University of Manchester and Manchester Breast Centre. My research vision is to provide a better understanding of the biology of breast cancer stem cells (BCSCs) with the aim of translating this knowledge into novel BCSC-targeting preventive and curative treatments. To this end, we use animal and cell models to study mammary gland development as well as initiation and progression of breast tumorigenesis. Qualifications: - PhD in Developmental biology (Dr. rer. nat, 2007), University of Goettingen, Germany MSc in Molecular Biology and Genetics (MSc., 2001), Bilkent University, Turkey BSc in Molecular Biology and Genetics (BSc., 1999), Bilkent University, Turkey Professional History: - Senior Lecturer at Brunel University, London, UK (2024- current) Intermediate Research Fellow, University of Manchester, UK (2017-2024) Postdoctoral Research Associate, Wellcome Trust Centre for Cell-Matrix Research, Manchester, UK (2014-2017) Senior Postdoctoral Fellow, German Cancer Research Centre (DKFZ), Heidelberg, Germany (2012-2013) Postdoctoral Fellow, German Cancer Research Centre (DKFZ), Heidelberg, Germany (2010-2012) Postdoctoral Fellow, Max Planck Institute for Biophysical Chemistry, Goettingen Germany (2010-2012)