PhD-Investigating the Role of Polarity Regulators in Pancreatic Ductal Adenocarcinoma (PDAC) Pathogenesis and Therapy
PhD @University of Liverpool posted 4 days agoJob Description
Overview
This interdisciplinary project integrates genetic, pharmacological and clinical approaches to investigate the biological and therapeutic relevance of polarity regulators in PDAC.
About this opportunity
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, with a five-year survival rate of ~10%. The lack of effective therapeutic options and the high incidence of chemoresistance underscore the urgent need to elucidate the molecular mechanisms driving PDAC development and progression.
Loss of cell polarity, a hallmark of epithelial neoplasia development, is critical during the progression from pancreatic preinvasive lesions to invasive PDAC. Altered expression of cell polarity regulators leads to dysregulation of oncogenic and tumour suppressive pathways, thereby promoting tumour progression. Further evidence indicates that inactivation of polarity genes drives resistance to chemotherapy and correlates with poor outcomes.
Emerging evidence, including work from our group and others, has demonstrated that mutations in polarity regulators are relevant genetic events in PDAC development. These findings highlight the need to investigate the tumour suppressive functions of polarity genes in PDAC and their clinical potential to identify novel strategies for patient stratification and therapeutic intervention.
Hypothesis
A better understanding of polarity signalling during PDAC development will reveal predictive biomarkers of drug response and molecular targets for therapeutic intervention in PDAC.
Aim and experimental strategy
This interdisciplinary project integrates genetic, pharmacological and clinical approaches to investigate the biological and therapeutic relevance of polarity regulators in PDAC.
1.- Molecular (viral-mediated shRNA/CRISPR) and cellular biology (2D/3D cell cultures) approaches will be employed to assess the tumour suppressive activities of polarity regulators in PDAC cells.
2.- Pharmacological and transcriptomic approaches will be used to identify molecular pathways associated with drug response.
3.- Clinical relevance of the findings will be evaluated in a collection of human PDAC samples.
Impact
This project introduces an innovative and comprehensive strategy designed to address critical unmet needs in PDAC research, with a strong focus on achieving meaningful translational impact. By targeting polarity regulators, we aim to uncover novel therapeutic targets and predictive biomarkers, ultimately striving to significantly improve clinical outcomes for PDAC patients.
Training
This PhD project will provide training in cancer biology and will offer a framework to develop their skills in molecular and cellular biology. Work will be undertaken in collaboration with members of the Pancreatic Group in Liverpool, including basic and clinical researchers. The student’s project will synergise with other research aiming at addressing critical gaps in PDAC pathogenesis and therapy.
Further reading
- Bermejo-Rodriguez C et al., Scribble Deficiency Promotes Pancreatic Ductal Adenocarcinoma Development and Metastasis. Cancer Res. 2024 Sep 16;84(18):2968-2984. doi: 10.1158/0008-5472.CAN-23-3419.
- Greenhalf W et al., Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial. J Natl Cancer Inst. 2014 Jan;106(1):djt347. doi: 10.1093/jnci/djt347.
- Pérez-Mancera PA et al., The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature. 2012 Apr 29;486(7402):266-70. doi: 10.1038/nature11114.
Who is this for?
This project is open to UK and international applicants. The project is suited to a student with at least a good BSc 2:1 in Cancer Biology, Biological Sciences, or related subjects, and evidence of lab experience.
Applications will be reviewed until a suitable candidate is appointed.
How to apply
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1. Contact supervisors
If you’re interested in this opportunity, in the first instance please email your CV and cover letter to project supervisor, Dr Perez-Mancera: pedro.perez-mancera@liverpool.ac.uk.
Project supervisors
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2. Prepare your application documents
You may need the following documents to complete your online application:
- A research proposal (this should cover the research you’d like to undertake)
- University transcripts and degree certificates to date
- Passport details (international applicants only)
- English language certificates (international applicants only)
- A personal statement
- A curriculum vitae (CV)
- Contact details for two proposed supervisors
- Names and contact details of two referees.
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3. Apply
Finally, register and apply online. You’ll receive an email acknowledgment once you’ve submitted your application. We’ll be in touch with further details about what happens next.
Fees and funding
Your tuition fees, funding your studies, and other costs to consider.
Tuition fees
UK fees (applies to Channel Islands, Isle of Man and Republic of Ireland)
Full-time place, per year – £5,006
International fees
Full-time place, per year – £31,250
fees stated are for 2025/26 academic year
Additional costs
We understand that budgeting for your time at university is important, and we want to make sure you understand any costs that are not covered by your tuition fee. This could include buying a laptop, books, or stationery.
Find out more about the additional study costs that may apply to this project, as well as general student living costs.
Funding your PhD
The project is open to both UK and international students. It is unfunded, and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project.
Assistance will be given to those who are applying to international funding schemes. The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £12,000 per annum. New self-funded applicants may be eligible for a tuition fees bursary.
If you’re a UK national, or have settled status in the UK, you may be eligible to apply for a Postgraduate Doctoral Loan worth up to £30,301 to help with course fees and living costs.
There’s also a variety of alternative sources of funding. These include funded research opportunities and financial support from UK research councils, charities and trusts. Your supervisor may be able to help you secure funding.
Scholarships and bursaries
We offer a range of scholarships and bursaries that could help pay your tuition fees and living expenses.
Duncan Norman Research Scholarship
If you’re awarded this prestigious scholarship, you’ll receive significant funding to support your postgraduate research. This includes full payment of your PhD fees and a cash bursary of £17,000 per year while you study. One award is available in each academic year.
Sport Liverpool Performance Programme
Apply to receive tailored training support to enhance your sporting performance. Our athlete support package includes a range of benefits, from bespoke strength and conditioning training to physiotherapy sessions and one-to-one nutritional advice.
