Group: Nutrition, Epigenetics and Cancer, School of Food Science and Nutrition, Faculty of Mathematical and Biological Sciences, University of Leeds, Leeds, UK
Key members: James L Thorne, Sam A Hutchinson
Contact: James L Thorne
By working alongside other researchers interested in cancer prevention at NIHR and the UK Therapeutic Cancer Prevention Network my group aims to find safe, affordable and effective routes to prevent cancer and improve survivorship. My collaborative links include industrial and academic partners from the USA, EU and UK that include synthetic chemists who are helping design novel LXR ligands, bioinformaticians for interrogation of next-generation sequencing data from cell lines and patient tumour samples, dieticians for food intervention studies and epidemiologists to investigate nutrient-disease interactions. I also have strong ties with the Leeds Teaching Hospitals Trust where consultants, surgeons and pathologists are involved in multiple aspects of patient recruitment for experimental medicine and nutritional intervention trials. Our research is supported by vital funding from breast cancer charities such as the Breast Cancer Research Action Group, and Breast Cancer UK.
Unusually for transcription factors, the nuclear receptor (NR) superfamily are ligand activated which means they are highly targetable by drugs, metabolites and nutrients. Agonist/antagonist abundance, epigenetic architecture and co-factor complexes all converge to regulate NR transcriptional capacity. NRs also regulate multiple miRNAs that repress transcriptional targets thus establishing coherent and incoherent feed-forward transcription loops. Several NRs sense and responds to endogenously produced cholesterol oxidation products, and to structurally related plant sterols. The oxysterol signaling capability of a tumour is a marker of reduced survival following therapy and appears to drive metastasis and chemotherapy resistance. We are therefore characterizing how the array of nutritional and pharmacological NR ligands can result in distinct transcription profiles and lead to different cellular capabilities such as stem cell-like characteristics, cellular migration, quiescence and the epithelial mesenchymal transition. The potential for therapeutic dietary (phytosterols/stanols) or pharmacological (statins) intervention in these oxysterol-NR activities is of significant clinical and public health interest for cancer prevention and therapy.
We currently have two vacancies:
1 - A scholarship for a PhD student (fees at UK/EU rates, bench fees, and stipend) to work on a project examining how phytosterols and oxysterols disturb the cancer cell plasma membrane
2 - A Post-Doctoral Research Associate position (UK Grade 7) examining how cholesterol metabolism in the breast cancer microenvironment may exacerbate chemotherapy resistance.
Key papers for ENOR
Biochimie ENOR Special Issue 2018. Title: Exploring the biophysical properties of phytosterols in the plasma membrane for novel cancer prevention strategies. Omar Fakih; Didem Sanver, PhD; David Kane; James L Thorne.