Medicine: Fully Funded Swansea & HMRI PhD Scholarship: Ovarian Cancer Chemoresistance

  • Phd
  • Full cost of tuition fees and an annual stipend
  • 6 May 2022

Medicine, Health and Life Science: Fully Funded Swansea University and HMRI PhD Scholarship: Therapeutic opportunities to tackle Ovarian Cancer Chemoresistance: addressing the Crosstalk between Adipocytes and tumours

Funding provider: Swansea University and Houston Methodist Research Institute (HMRI)

Subject areas: Medicine, Health & Life Science

Project start date:

  • 1 October 2022 (Enrolment open from mid-September)

Project supervisors:

  • Professor Deya Gonzalez (Swansea)
  • Dr Francesca Taraballi (HMRI)

Aligned programme of study: Medical and Healthcare Studies, Swansea University & Houston Methodist Research Institute, Texas, Collaborative PhD

Mode of study: Full-time

Project description:

Ovarian cancer (OC) is the fifth most common cause of cancer death in women and accounts for more UK deaths than all of the other gynaecological cancers put together. Over 7,000 women are diagnosed with OC every year in the UK and 4,200 will die. OC symptoms are often vague early on and many women are not diagnosed until after the cancer has grown and spread to other parts of the body. Less than half of women with OC survive five years from diagnosis with many not responding to current treatments. Platinum-based drugs (such as cisplatin and carboplatin) are the most widely used chemotherapy drugs in ovarian carcinoma (85% patients will receive this treatment), but their efficacy is not satisfactory. Targeted therapeutic approaches including bevacizumab and Olaparib, recently added to standard clinical practice and provide a modest improve on survival rates. However, OC remains a complex disease to treat, owing to the high chemotherapy‐resistance emergence rate.

Tumour progression and response to therapy depend on the molecular features of the cancer cells and on their interaction with the surrounding environment, either at the primary or at the metastatic site. Recently, we identified the presence of immune‐active components within the tumour nodules and the ascites raising the question of why the therapeutic potential of immunotherapies is still limited in OC settings (Pisano et al., 2021; Clin Transl Med.). A primary target of OC local metastasis is the adipocyte-rich omentum, which regulates inflammation, angiogenesis, immune response and metabolism. The transformed omentum and tumour-associated adipocytes play an important role in generating a pro-metastatic tumour microenvironment (TME) within the peritoneal cavity including the promotion of a chemoresistance phenotype in OC tumours.

In this project, we will use exosomes secreted from omental adipocytes, isolated from cancer patients, to explore the signalling mechanism mediated by these vesicles within the cells of the tumour microenvironment. In parallel we will evaluate the effect of exosomes loaded with chemotherapeutic drugs to improve efficacy of drugs with poor solubility. This will allow us to identify key signalling exosomal components and determinants of cell fate and chemoresistance properties of the TME with the ultimate aim of developing better treatments.

The project will use an optimised exosome isolation and characterisation platform as well as 3D cancer models developed by Gonzalez. These models will allow us to elucidate the uptake pathways used by exosomes derived from adipocytes within the tumour microenvironment. At HRMI the student will then develop biomimetic nanoparticles that resemble exosome vesicles to investigate their potential as carriers for targeted drug delivery systems. At HMRI they are pioneers of biomimetic nanoparticles as summarized in their very recent work. Zinger et al. (Nanomaterials 2020, ACS Nano 2021, Advanced Science 2021, Advanced Functional Materials 2021). This project could lead to the identification and development of novel anticancer drugs. The student will be supervised by Prof Gonzalez (SU, OC and drug development expertise) and Houston Methodist academic, Dr Taraballi (drug loading, Synthesis and functionalization of nanoparticles for targeted cancer drug delivery) joining vibrant, multidisciplinary research environments composed of academics, clinicians, PhD students, post-docs and technicians.

The PhD is funded by Swansea University and Houston Methodist, and as such the student will spend the first year at Swansea University, the following 2 years at the Houston Methodist Research Institute and the fourth year at Swansea University.

Eligibility

Candidates must normally hold an undergraduate degree at 1st class level and/or a master’s degree with a minimum overall grade at ‘Distinction’ (or Non-UK equivalent as defined by Swansea University). Subject backgrounds in molecular biology, medical genetics, genetics, biochemistry, medical biochemistry or a related discipline are considered.

Applications are sought from individuals with experience in:

  • Gene/Protein expression analysis (Quantitative Real Time PCR, Western blot, ELISA)
  • Tissue culture techniques
  • Previous experience working with patient samples

English Language requirements: If applicable – IELTS 6.5 overall (with at least 6.5 in each individual component) or Swansea recognised equivalent.

This scholarship is open to candidates of any nationality.

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Benefits

This scholarship covers the full cost of tuition fees and an annual stipend of £16,062 for four years.

Additional research expenses will also be available.

Application

Please visit our website for more information.

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