Understanding and exploiting sterol metabolism in chronic kidney disease and cancer
Code: BC-DTP_2026_10
Title: Understanding and exploiting sterol metabolism in chronic kidney disease and cancer
Primary Supervisor: Barrie Peck
Email: b.peck@qmul.ac.uk
Institute: Barts Cancer Institute
Secondary Supervisor: Andy Fintch
Email: a.finch@qmul.ac.uk
Institute: Barts Cancer Institute
Lay Summary:
Chronic Kidney disease (CDK) and Clear cell Renal Cell Carcinoma (ccRCC) are very interesting diseases because they have very distinct ways of eating and processing energy (metabolism), meaning they store large amounts of fats within the cells. This is such a strong part of their biology, for example, it is how doctors identify and diagnose that the kidney has cancer cells in it. We have turned off hundreds of proteins involved in metabolism in these cells and shown that they are very dependent on the protein DHCR24, but the reason why is completely unknown. In this project we will discover why cells that exhibit CKD and cancer cells are dependent on DHCR24. Importantly, we have designed and synthesized new selective drugs that target DHCR24 (better than any known drug) and believe these could be future treatments for CKD and cancer. This project will show that we can target DHCR24 in these cells and provide the rationale and know-how for testing this in a clinical trial.
Aims:
Our overarching objective for this PhD studenship is to further understand how DHCR24 influences sterol metabolism in CKD-induced cells and ccRCC cells. Together we will:
- Investigate the regulation of DHCR24 and how its inhibition selectively impacts metabolism, particularly the sterolome.
- Further determine how DHCR24 inhibition induces ferroptosis that arises from the Endoplasmic Reticulum.
- Validate the targeting of ER-initiated ferroptosis in 3D models of CKD and cancer.