Handbrake on hysterectomy: Developing a personalised and fertility sparing pharmacological therapy for uterine fibroid-induced symptoms

Fibroids are common non-cancerous tumours of the uterine wall affecting millions of women of childbearing age around the world. They cause heavy menstrual bleeding (HMB), subfertility and exert pressure on the adjacent organs, making women feel pain and discomfort. The prevalence increases with age and 1 in 2 women have fibroids by 50-years.

One in four women experience HMB, which reduces quality of life; women may not be able to manage the activities in their day-to-day lives, perform well in their education or job, and have difficulties in their personal and family life due to symptoms caused by fibroids. Although common, there are no curative treatments for fibroids that preserve the uterus and thus, fertility, and many women undergo hysterectomy for this indication.

In fact, fibroids are the main reason for hysterectomy in the world. Many women delay their childbearing until later in life, thus, fibroids being more prevalent with age cause severe symptoms and hysterectomy will prevent them conceiving. Finding fertility-sparing medical treatments that stops the growth of fibroids until menopause will improve the quality of life of millions of women, and reduce the morbidity and mortality associated with risky major surgery.

Angiogenesis is essential for fibroid growth and uterine cellular ageing and age-associated hormonal imbalance are proposed yet understudied mechanisms that initiate fibroid growth.

Aim: This PhD studentship seeks to improve our understanding of how different each fibroid is, both in the same woman and between women, to understand why they do not all respond to available treatments in the same way. It also aims to identify druggable targets to develop future novel treatments.

Environment and learning experience: The successful student will be taught latest state-of-the-art techniques at a multi-omics level. Combining transcriptomics, quantitative proteomics and advance data integration and data science techniques and will provide insights on the pathophysiology of the disease. All omics techniques will be undertaken in partnership with specialised research facilities at the University of Liverpool.

The student will also learn, Sequential Window Acquisition of All Theoretical (SWATH) mass spectrometry proteomics analysis and development of physio-mimetic multicellular 3D complex in vitro models from patient derived tissue and general lab and drug testing skills.

Modern science is multidisciplinary and as such, the supervisory team will provide expertise exemplifying the diverse range of skills offered through this exciting and clinically relevant project that includes clinical/translational research. Expected outcome:

This research will benefit women with fibroids who want either to preserve their fertility or avoid risky surgery. It will directly test the clinical application of the data generated in the laboratory. Using the models generated, the candidate can identify and choose effective treatments from a large number of available drugs that have already proven to be safe to use in humans to test in future clinical trials.

This will significantly shorten the time taken to develop new treatments for fibroids and will also provide a platform to tailor personalised treatment regimens for the millions of women impacted by fibroids.