Lipid-determined differences in response to chemotherapy between Black and White breast cancer patients

Targeted treatments for triple negative breast cancer (TNBC) are still not available despite this subtype disproportionately contributing to breast cancer (BCa) mortality and disproportionately affecting ethnic minority groups. Racial differences in lipid processing are unexplored in the context of explaining why Black women are significantly more likely to develop TNBC and why treatment is less efficacious than in White women. The objectives of this project are to understand lipidome differences in TNBC cells between chemotherapy responders and non-responders, and between Black and White patients. We hope this project will lead to a better understanding of why Black women are more likely to get TNBC than White women and why treatment is less efficacious.

<p style="text-align:justify; margin-top:8px; margin-bottom:8px"><span style="font-size:11pt"><span style="line-height:150%"><span style="font-family:&quot;Calibri Light&quot;,sans-serif"><span style="color:black">Targeted treatments for triple negative breast cancer (TNBC) are still not available despite this subtype disproportionately contributing to breast cancer (BCa) mortality and disproportionately affecting ethnic minority groups. The role of lipids in severity TNBC and chemoresistance is emerging and beginning to inform understanding that may lead to therapeutic targeting of this pathway to help improve outcomes. Racial differences in lipid processing are unexplored in the context of explaining why Black women are significantly more likely to develop TNBC and why treatment is less efficacious than in White women. Chemotherapy efficacy in TNBC has emerged as particularly reliant on, and sensitive to, changes in lipid profile (e.g. omega-3s improve response to BCa therapy; oxysterols confer chemoresistance; obesity linked dyslipidaemia is prognostic for poor TNBC outcomes). Many lipid targeting therapies in clinical use for other diseases may therefore be appropriate in the TNBC setting. The mechanisms of how lipids alter TNBC chemoresponse to treatment are largely unknown and have not been systematically evaluated, thus limiting the potential application of lipid targeting nutritional and pharmacological interventions. The objectives of this project are to: characterise the lipid profile of tumours derived from Black and White TNBC patients; establish the balance and ratios of lipid content and proteome between tumours of TNBC patients who respond to chemotherapy compared to those who don&rsquo;t; determine associations between nutritional status, lipid balance, and chemoresponse in breast cancer patients; compare proteomic changes in TNBC induced by lipids associated with chemoresponse or with lack of chemoresponse.</span></span></span></span></p>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is <em>Lipid-determined differences in response to chemotherapy between Black and White breast cancer patients</em> as well as&nbsp;<a href="https://environment.leeds.ac.uk/food-nutrition/staff/7156/dr-james-l-thorne">Dr James Thorne</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.5 overall with at least 6.0 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<p>This project is currently not funded so if you are interested you will also need to apply for a Scholarship to fund your studies (to include your living costs, University fees, and experimental costs). If you think you may be eligible for one of the following funding routes, please speak to the project lead, Dr James Thorne, for further information.</p> <ol type="1"> <li>You intend to apply for a PhD Sholarship for UK under-represented groups (https://www.leeds.ac.uk/research-funding/doc/scholarships-under-represented-groups) (UK applicants only).</li> <li>You are eligable and intend to apply for a Leeds Sanctuary Scholarship (https://www.leeds.ac.uk/international-students/doc/sanctuary-scholarship)&nbsp;(overseas student now resident in the UK).</li> <li>You will apply to the Leeds Doctoral Scholarship scheme (https://phd.leeds.ac.uk/search?clive=leeds-pgr-web-funding&amp;query=Leeds+doctoral+scholarship) deadline 1^st&nbsp;March 2024&nbsp;(UK applicants).</li> <li>You have secured a Scholarship to study for a PhD from your home country and are seeking a host laboratory in the UK (overseas&nbsp;applicants).</li> <li>You are eligable and intend to apply for a Chinese Scholarship Council award and are seeking a host laboratory (overseas applicants). Deadline to approach supervision team is 4^th&nbsp;December 2023. Alternatively, consider applying for a 2025 start.</li> <li>You are eligable and intend to apply for a Commonwealth Scholarship Council award and are seeking a host laboratory (overseas applicants). Deadline is region specific. Please check local guideance.</li> <li>You are a self-funding student (UK or overseas).</li> </ol> <p>Please note &ndash; different schemes have different application&nbsp;deadlines.</p>

<p>For further information please contact the Graduate School Office or email the lead supervisor:&nbsp;<a href="mailto:EMAIL@leeds.ac.uk">j.l.thorne@leeds.ac.uk</a>.</p>