Dr James L Thorne
- Position: Associate Professor of Cancer, Nutrition, and Epigenetics
- Areas of expertise: epigenetics; cancer; nutrition; cholesterol metabolism; oxysterols; phytosterols; chemoresistance; metastasis; diet; nutraceuticals; gene expression; molecular biology; miRNA; histone code.
- Email: J.L.Thorne@leeds.ac.uk
- Phone: +44(0)113 343 0684
- Location: p2.35 SFS&N@Parkinson
- Website: The Leeds Breast Cancer Research Group | Twitter | LinkedIn | Googlescholar | Researchgate | ORCID
I am an Associate Professor of Cancer, Epigenetics, and Nutrition in the School of Food Science and Nutrition. My Research Group’s aims are to uncover how, at the molecular level, nutrition and diet can alter the risk of developing cancer, how nutrition can influence the efficacy of cancer treatments, and whether diet and lifestyle interventions can be adopted by patients to produce tangible improvements in their prognosis. I obtained my undergraduate BSc (2:1) in Genetics from Queen Mary University of London, before going on to complete an MRes at University College London, and a PhD from Imperial College. I have undertaken post-doctoral research positions at the Universities of Birmingham and Leeds. In Birmingham I researched the role of Nuclear Receptor biology in the development and progression of prostate cancer under the tutelage of Moray Campbell (now at Ohio State). I specialised in defining the epigenetic changes that occurred in the prostate in response to the Vitamin D and cross talk between members of the Nuclear Receptor superfamily. I then moved to the Faculty of Medicine at the University of Leeds where I extended my laboratory skills by studying how components of the NFkB pathway combined with the histone code to influence elongating RNA polymerase activity. At this time I developed an interest in how cancer specific transcription and epigenetic mechanisms could lead to chemotherapy resistance in cancer patients, in the laboratory of Thomas Hughes. I continue to collaborate with Dr Hughes and other members of the Faculty of Medicine by co-supervision of post-graduate research students, and regular breast cancer focused meetings supported through membership of the Leeds Breast Cancer Research Group.
My group collaborates with researchers from the NIHR Nutrition and Cancer Collaboration, in the “Molecular Mechanisms: Experimental to First-in-Human” workstream and the European Network for Oxysterol Research (ENOR). If you are interested to join either organisation, please get in touch. I have particularly close ties with the Analytical Chemistry group at the University of Oslo where PhD students are co-supervised with Dr Hanne Røberg-Larsen, and with Bioinformatic scientist Dr Seba Battaglia at Roswell Park Memorial Institute. I also work closely with clinical academics at the Leeds Teaching Hospitals Trust where consultant surgeon (Dr Baek Kim), radiologist (Dr Nisha Sharma) and pathologist (Dr Eldo Verghese) are involved in multiple aspects of my research for experimental medicine and nutritional intervention trials.
Diet, Epigenetics and Cancer Group Members
- Dr Giorgia Cioccolini (Breast Cancer Action; Post-doctoral Research Associate) "Diet, tumour micro-environment and breast cancer progression" 2018 - present.
- Mr Alex Websdale (Breast Cancer UK Scholarship; Post-Graduate Researcher), "Metabolite signalling in the breast tumour microenvironment" 2018 - present.
- Ms Chrysa Soteriou (Leeds Interdisciplinary Scholarship; Post-Graduate Researcher), "Dietary manipulation of the cancer cell plasma membrane" 2018 - present.
- Ms Priscilia (Lia) Liantro (Leeds International Doctoral Scholarship; Post-Graduate Researcher) "LXR, metastasis and Triple Negative Breast Cancer" 2018 - present.
- Mr Zhi (Rex) Chong (International Post-Graduate Researcher) “Genetic, epigenetic and metabolic regulation of LXR activity” 2019 - present.
- Ms Emtenan Jefrei (Saudi Scholarship; Post-Graduate Researcher) “Epigenetic regulation by phytosterols”
Co-supervised PhD Students
- Ms Xiaoying Tian 2020 – present (with Dr J.B Moore)
- Mr Cancan Huang 2018 – present (with Prof A. Mackie)
- Ms Kartika Nugraheni 2018 – present (with Dr C. Boesch)
- Ms Zixuan Zhang 2018 – present (with Dr J.B Moore)
- Dr Sam Hutchinson – PhD 2016 - 2019. Now PDRA at the Institute of Cancer Research.
- Dr Baek Kim – Medical Doctorate 2011 - 2014 (with Dr Thomas Hughes). Now consultant Breast Surgeon at Leeds Teaching Hospitals Trust.
- Dr Robyn Broad – PhD 2015 - 2019 (with Dr Thomas Hughes).
- Ms Anna Nicholls – MRes 2019 – 2020 (with Dr L. Matthews). Now completing medical degree.
- Ms Nerea Pajares – Erasmus+ 2017.
- Mr David Kane – Research Assistant - BCRAG 2016-2017. Nutritional regulation of tumour cell energy balance.
- Mr Fraser Chardwick – Research Technician Breast Cancer UK 2016-2017. Technician, oxysterol measurements in human tumour tissue.
- Mr Hugues Patout – Erasmus+ 2016
- Student Equality and Inclusivity Officer
- Widening Participation Officer
- School Disability Lead
The Role of Nuclear Receptor Superfamily in Cancer
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 choices, and NRs regulate an array of cellular choices including apoptosis, proliferation and cellular energy metabolism (The Warburg Effect). NRs also regulate multiple miRNAs that repress transcriptional targets thus establishing coherent and incoherent feed-forward transcription loops. My group and our collaborators are developing new tools for studying how NRs interact, and are attempting to define how NR can cross-talk in the cancer setting. Owing to the ligand-dependant nature of many NRs, they are exceptional targets of pharmacological agents, metabolites, and perhaps most importantly, dietary factors and nutrients. Using dietary modulation of NR signalling, we hope to provide a robust evidence base for dietary and lifestyle interventions that can empower patients to make changes to the diet and lifestyle and identify novel therapeutic regimens, that result in tangible improvements to a cancer prognosis.
Cholesterol, oxysterols and breast cancer
My research group’s core interests are focussed heavily on how cholesterol metabolism in the breast tumour microenvironment influences patient outcomes. The tumour microenvironment not only consists of cancer cells, but an array of ‘normal’ cells including those heavily laden with fat (adipocytes), immune cells (e.g. macrophages, lymphocytes), and structural support cells (fibroblasts). These non-tumour cells are metabolically and epigenetically reprgrammed by the growing tumour, to support the survival, growth and spread of the cancer cells. We study how the very earliest metabolic changes to cholesterol (synthesis of oxysterols) is distorted in these non-cancer cells of the tumour, along cholesterol’s journey to become anything from bile acids to steroid hormones and an array of other endocrine and paracrine signalling molecules. Oxysterols are emerging as key regulators of cancer cell biology and they regulate gene expression in normal and malignant tissue through the Liver X Receptor (LXR). 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.
These ‘intermediate’ oxysterol metabolites are potent signalling molecules in their own right, and our recent observations (supported by grants from Breast Cancer Action and Breast Cancer UK) show that although the oxysterol profiles are similar between breast cancer subtypes (Soleheim et. al., 2019), there are differences between breast tumour subtypes in how they respond to cholesterol (Hutchinson et. al., 2019a). We have also found that plant derived cholesterol mimics (phytosterols and phytostanols) can supress transcriptional activation of key cancer promoting pathways following activation by cholesterol metabolites (Hutchinson et. al., 2019b). These plant cholesterol mimics are already available to consumers and are clinically indicated for benign prostate hyperplasia and hypercholesterolaemia. With the support of Breast Cancer Action we are now running a pilot clinical trial (clinicaltrials.gov NCT04147767) to establish how non-tumour cells found in the tumour microenvironment may be responsible for promoting chemotherapy resistance, and if these pathways can be supressed by nutrients that compete with cholesterol for access to the transcriptional regulators.
Our funding partners
Looking for a PhD position?
We periodically have funded PhD positions available and are always looking for bright and motivated candidates for PhD research. If you have a project idea, or would like to study for a PhD in my laboratory, then we welcome you to get in touch. We are supporting UK/EU applicants to apply for scholarships such as the Leeds Doctoral Program, for Chinese nationals through the Chinese Scholarship Council (deadline 6th January), and for Commonwealth citizens thought the Commonwealth Fund, and I am proud to say, if you have experienced a forced migration you can apply to the Leeds University Sanctuary Scheme. Self-funding PhD applicants, or those with scholarships from their home institutes and governments are also welcome to apply. Prospective PhD students are encouraged to contact me, with a CV and a cover letter explaining their motivtions for applying, for information about potential projects. An interest in epigenetics, cancer and dietary and/or clinical intervention is beneficial. In the future we will be exploring the potential for therapeutic dietary (phytosterols/stanols) or pharmacological (statins) intervention in oxysterol-NR activity in cancer patients, to build on our recent observations and hypotheses. In my laboratory you will learn a range of epigenetic, cell and molecular biology tools to investigate these cancer pathways, and how cancer cell biology can be manipulated by components derived from, or modulated by the diet.
- NIHR Nutrition And Cancer Collaboration
- ECMC UK Therapeutic Cancer Prevention Network
- European Network for Oxysterol Research
- The British Endocrine Society
- The Nutrition Society
- European and British Associations for Cancer Research
I am module manager for Undergraduate and Postgraduate courses at the School of Food Science and Nutrition, teach on a variety of other modules in my School and the School of Medicine and act as personal tutor. If you are currently in the School of Food Science and Nutrition either at UG or PG level and think you would like to do you research project in my group then please get in touch to discuss project options. Typically I offer student projects on ‘Diet-tumour molecular interactions.’ The projects that I can offer include molecular and cell biology laboratory work (siRNA transfection, qPCR, cell survival analysis, chemotherapy efflux assays), computer based analysis of Next Generation Sequencing datasets (Chromatin IP and RNA-Seq), systematic literature review, or a combination of the above. Previous undergraduate and postgraduate students in my lab have gone on to publish with me as co-authors. I especially welcome any students who have this goal.
Research groups and institutes
- Food Chemistry and Biochemistry
- Nutritional Epidemiology
- Obesity, Cancer and Metabolic Disease
- Human Nutrition and Lifestyle Intervention
Current postgraduate researchers
<li><a href="//phd.leeds.ac.uk/project/1011-cancer:-mechanisms-of-nutrient-metabolic-regulation-of-cancer-chemotherapy-resistance">Cancer: Mechanisms of nutrient-metabolic regulation of cancer chemotherapy resistance</a></li>
<li><a href="//phd.leeds.ac.uk/project/264-diagnosing-breast-cancer-with-dna-entrapment-and-nanopore-detection">Diagnosing breast cancer with DNA entrapment and nanopore detection</a></li>
<li><a href="//phd.leeds.ac.uk/project/263-how-do-dietary-sterols-alter-cancer-cell-signalling-originating-from-the-plasma-membrane?">How do dietary sterols alter cancer cell signalling originating from the plasma membrane?</a></li>