Molecular and Cell Biology of Lipid Sensing Nuclear Receptors in Cancer at University of Leeds on FindAPhD.com

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Dr J L Thorne Applications accepted all year round Self-Funded PhD Students Only

Leeds United Kingdom Nutrition Food Sciences

About the Project

The nuclear receptor (NR) superfamily are ligand activated transcription factors. This means NRs can integrate signals from xenobiotics (drugs, nutrients), metabolites, and hormones to regulate gene expression and cell fate decisions. NR function is often disrupted in cancer cells. Many lipids species are NR ligands, and are abundantly found in cells as a broad group of loosely related biomolecules. Lipids are essential to cellular structure, membrane function, and are also precursors to an array of hormones, vitamins, bile acids and steroids - many of which function as NR ligands. Lipid levels are constantly monitored and regulated by the NR superfamily, but as with NRs, many lipids are become deregulated in cancer.

During this PhD you will explore the molecular pathways that allow NRs to link nutrition, metabolism, and cell fate decisions, in the cancer setting. Using modulation of NR signalling with ligands that represent diverse nutrient and metabolic classes of compounds, and a range of epigenetic and cell biology laboratory methods (ChIP, NGS, immuno-based technologies), you will investigate the molecular mechanisms that underpin the dietary and lifestyle patterns that cause cancer and prevent successful cancer therapies.

Funding Notes

This project is currently not funded so if you are interested you will also need to apply for a Scholarship to fund your studies (to include your living costs, University fees, and experimental costs. If you think you may be eligible for one of the following Scholarships, please speak to the project lead, Dr James Thorne, for further information.

References

Recent publications from our research group are listed here:
Hutchinson SA€, Websdale A€, Cioccoloni G, Røberg-Larsen H, Lianto P, Kim B, Rose A, Soteriou C, Wastall LM, Williams BJ, Henn MA, Chen JJ, Ma L, Moore JB, Nelson E, Hughes TA* and Thorne JL* (2021). Liver x receptor alpha drives chemoresistance in response to side-chain hydroxycholesterols in triple negative breast cancer. Oncogene doi.org/10.1038/s41388-021-01720-w
Soteriou C, Connell S, Kalli A, Tyler AII, Thorne JL* (2021). Advances in understanding of how lipids in the plasma membrane initiate and alter cancer cell signalling pathways using multidisciplinary methodology. Prog in Lipid Research. doi:10.1016/j.plipres.2020.101080
Want MY, Takemasa T, Singh P, Thorne JL, Matsuzaki J, Karasik E, Gillard B, Koya R, Lugade A, Odunsi K, Battaglia S* (2020). WHSC1/NSD2 regulates immune infiltration in prostate cancer. Journal for ImmunoTherapy of Cancer.
Cioccoloni G, Soteriou C, Websdale A, Wallis L, Zulyniak MA, and Thorne JL* (2020). Phytosterols and phytostanols and the hallmarks of cancer: a systematic review and meta-analysis of whole organism models. Critical Reviews in Food Science and Nutrition. doi: 10.1080/10408398.2020.1835820
Thorne JL*, Moore JB, Corfe BM (2020). Nutrition and cancer: evidence gaps and opportunities for improving knowledge. Proceedings of the Nutrition Society. DOI: doi.org/10.1017/S0029665120000099.