Elucidating the mechanisms of early-stage breast cancer initiation

Using both transgenic cell lines and transgenic mouse models available in our research group, this project will determine the causal effects of increased accumulation of Reactive Oxygen Species (ROS) caused by HER2 overexpression on distinct stromal cell populations of mammary glands. These will be analysed using various state-of-the art omics methods, flow cytometry and various histological staining methods.

To determine the biological effects of the known epidemiological breast cancer risk factors (e.g. tissue stiffness, early menarche, late menopause, obesity, parity), this project will utilise both the transgenic animal models as well as 3D primary culture methods to elucidate their potential influence on alterations of tissue architecture, ROS or mutation rates during the earliest stages of HER2-driven breast tumourigenesis. These will be analysed using live-imaging methods, histology and whole-genome sequencing.

Gurler S. et. al. HER2 overexpression initiates breast tumorigenesis non-cell-autonomously by inducing oxidative stress in the tissue microenvironment. BioRXiv, 2024

Supervisor's interests
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 (Gurler S. et.al., 2024), we aim to better understand the role of the HER2 oncogene in the initiation of breast cancer through a non-cell autonomous mechanism, and to identify the molecular and cellular mechanisms underlying the effects of known epidemiological breast cancer risk factors on HER2-driven breast tumourigenesis.

How to apply

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

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.
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.
Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.

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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)