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Lung adenocarcinoma (LUAD) is treated with chemotherapy and immunotherapy which is largely ineffective. The team show LUAD patients may benefit from epigenetic differentiation therapy. This project utilises human and mouse models of LUAD to define the mechanisms of epigenetic differentiation therapy in order identify biomarkers predictive of response, and synergistic therapies. These studies will demonstrate the utility of epigenetic differentiation therapy in LUAD, leading to successful translation.

Bacterial cell walls are decorated by ‘blebs’, or vesicles, which are released to the surrounding medium during growth. These vesicles play important roles in communication between bacteria and host cells. Vesicles from the stomach bacterium, H. pylori, carry a protein with cancer-causing properties. The proposed research project will demonstrate how these vesicles alter host cell functions, leading to cancer. This research will describe a new mechanism by which bacteria can cause cancer.

Pelvic organ Prolapse (POP) is a hidden, debilitating disorder affecting 25 per cent of women causing sexual, bladder and bowel dysfunction. POP is the herniation of the uterus, bladder, or bowel into the vagina due to childbirth injury. Surgical treatment often fails and the use of vaginal mesh has been banned due to unacceptable side effects. There is no cure and no means to identify early damage. The team is developing novel 3D printed therapies using stem cells and nanotechnology to prevent POP.

This program of work will uncover the role of the endometrial environment in stillbirth, elucidating the foundation of placental issues and ultimately lead to new strategies and interventions for stillbirth prevention.

Disorders of sexual development (DSDs) are surprisingly common, with an estimated frequency of one per cent. However, half of DSD cases remain genetically undiagnosed. The team will identify new causes of DSD. The DNA from patients will be sequenced and patient-specific cell culture systems developed to understand alterations in sex development. The team expect to identify novel DSD genes which will be incorporated into DSD panels globally to raise diagnostic yield, which is currently at 40 per cent.

The steroid hormone aldosterone controls salt balance and hence, blood pressure. It also has been shown to have a significant role in cardiac failure. Although drugs that block the aldosterone receptor are beneficial in the treatment of heart failure, they are limited by potassium retention in the kidney. In order to develop tissue-specific blockers of the aldosterone receptor, it is necessary to identify mechanisms by which the receptor can be activated and/or blocked in these tissues.