Antisense technologies as potential treatments for Cushing’s disease

Cushing’s disease is a devastating condition caused by a pituitary corticotroph tumour that over-expresses the proopiomelanocortin gene (POMC) and secretes high levels of ACTH. The latter drives the adrenals to produce excess cortisol causing the clinical state that incurs a 5-fold excess mortality. Pituitary surgery is the standard treatment but leaves approximately 40-50% without permanent cure. Current drug-based treatments can have deleterious side-effects. At present, there is an unmet clinical need in terms of medical therapies that will alleviate Cushing’s disease.

Overall, an ideal therapy for Cushing’s disease would be specific and effective by selectively reducing circulating ACTH, acting rapidly, minimising damage to other pituitary functions, and resolving clinical features. Such required effects have led to the investigation of antisense technologies as possible therapeutics for Cushing’s disease, whereby small inhibitor (si)RNA molecules or antisense oligonucleotides (ASO) are designed to silence expression of the POMC gene.

The PhD student will undertake a programme of study to advance the characterisation and testing of antisense molecules against POMC as well as researching and developing delivery modes. They will train in a wide range of methodologies including cell culture, cell transfections, molecular biology techniques, ELISA, and FACS. Gaining a variety of transferrable skills is an expected outcome. Finally, joining a research group of dedicated academics, postdoctoral researchers and PhD students will provide a stimulating learning environment.

Entry requirements: Candidates must have a first class or upper second class honours degree or significant research experience in a relevant discipline.

How to apply: Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying

Please clearly state the prospective main supervisor Dr Helen Kemp in the respective box, and select School of Medicine & Population Health (Oncology & Metabolism) as the department.

Enquiries: Interested candidates should, in the first instance, contact Dr Helen Kemp (e.h.kemp@sheffield.ac.uk)

Proposed start dates: 1st March 2024, 1st October 2024