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Redefining the use of steroids in endometriosis: key mechanisms and new solutions


   Faculty of Biology, Medicine and Health

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  Prof K Marshall, Dr D Fischer  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Endometriosis is a debilitating condition that affects an estimated 190 million women of reproductive-age worldwide [1]. In endometriosis, cells similar to the lining of the uterus typically form lesions around the bowel, ovaries and bladder, causing chronic inflammation and scarring. Major symptoms of pelvic pain and infertility are eased by their removal during laparoscopy (keyhole surgery). However, management is a challenge due to high rates of disease recurrence (>60%) [2] and adverse side effects from hormonal treatments that prevent users from becoming pregnant.

One way to mitigate these issues is to use a targeted approach to suppress oestrogen synthesis, which has a major role in the invasion, angiogenesis, proliferation and survival of endometriotic cells. Two emerging candidates include the aldo-keto reductase 1C3 (AKR1C3) enzyme and peroxisome proliferator-activated receptor (PPAR)γ pathway. However, further research is warranted to improve insights into their contributions to disease severity and recurrence.

The aim of this project is two-fold: 1) to distinguish molecular differences according to endometriosis subtype and 2) to test the effect of new pharmaceutical agents and/ or delivery systems to prevent risk of recurrent lesion growth.

Endometriosis tissues will be collected from consenting women of known provenance undergoing routine laparoscopic surgery at the Pennine Acute Hospitals NHS Trust in line with Local Ethics regulations. Histology, immunocytochemistry and molecular techniques will be performed to assess receptor and protein expression according to clinical history and patient-reported symptoms. A cell-based modelling approach will also be used to identify the pharmacological effect of promising AKR1C3, PPARƳ and progestin analogues alone or encapsulated in our hydrogel scaffold to evaluate their potential therapeutic value. This translational research would help us explore preventive interventions or new therapies, enabling clinicians to develop a tailored patient care plan.

The supervisory team has diverse but complementary expertise in reproductive endocrinology and biochemistry, offering the student a multidisciplinary skill-set. Training will be provided in primary cell culture, histology, functional pharmacology, biochemical and molecular techniques as well as experimental design and data analysis.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Genetics

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk


Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/

References

1] Zondervan, Becker, Missmer (2020) Endometriosis. N Engl J Med. 382: 1244-56.
[2] Saraswat, Ayansina, Cooper, Bhattacharya, Horne, Bhattacharya (2018) Impact of endometriosis on risk of further gynaecological surgery and cancer: a national cohort study. BJOG. 125:64-72
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