School of Food Science and Nutrition

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James Thorne

University of Leeds Academic Fellow
Research section: Food Chemistry and Biochemistry

Contact details

Room: P2.21b
Tel: +44 (0)113 3430684
Email: J.L.Thorne@leeds.ac.uk

Keywords

Breast Cancer
Oxysterol
Phytosterols
Epigenetics
miRNA
Stem Cells

Research interests

I am a University Academic Fellow and Junior Group Leader here in the School of Food Science and Nutrition. My laboratory uses a range of epigenetic, cell and molecular biology tools to investigate how cancer cell biology can be manipulated by components derived from and modulated by the diet. Oxidised cholesterol metabolites (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) pathway (Fig-1).

Unusually for a transcription factor, LXR is ligand activated which means it is a highly targetable. Agonist/antagonist abundance, epigenetic architecture and co-factor complexes can all converge to regulate LXR's transcriptional capacity. LXR also represses multiple miRNAs that would otherwise repress its transcriptional targets; LXR is thus implicated in establishing coherent feed-forward transcription loops.

LXR senses and responds to endogenously produced oxysterols and to structurally similar plant phytosterols and selected polyphenols. The oxysterol signaling capability of a tumour is a marker of reduced survival following therapy (Fig-2).

We are therefore characterizing how the array of natural LXR 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-LXR activities is of significant clinical and public health interest for cancer prevention and therapy.

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.

Prospective UK, EU and international PhD students are encouraged to contact me for information about potential projects. An interest in epigenetics, cancer and dietary and/or clinical intervention is beneficial.

Thorne lab group members


  • Ms. Sam Hutchinson - (LARS) PhD Student, Oxysterol regulation of chemotherapy resistance in breast cancer
  • Ms. Nienyun Hsu - PhD Student, Modelling nuclear receptor family activity in breast cancer
  • Mr. David Kane - (BCRAG) Research Assistant, Nutritional regulation of tumour cell energy balance
  • Ms. Sara Viney - (Breast Cancer UK) Technician, oxysterol measurements in human tumour tissue
  • Ms. Nerea Pajares - (Erasmus+) visiting student (2017), LXR-chromatin interaction in breast cancer
  • Mr. Hugues Patout - (Erasmus+) visiting student (2016), solubility of oxysterols

Shared PhD Students


Publications

Thorne JL, Campbell MJ Nuclear receptors and the Warburg effect in cancer International journal of cancer. Journal international du cancer 137 1519-1527, 2015
DOI:10.1002/ijc.29012
View abstract

Kim B, Stephen SL, Hanby AM, Horgan K, Perry SL, Richardson J, Roundhill EA, Valleley EMA, Verghese ET, Williams BJ, Thorne JL, Hughes TA Chemotherapy induces Notch1-dependent MRP1 up-regulation, inhibition of which sensitizes breast cancer cells to chemotherapy BMC Cancer 15 -, 2015
DOI:10.1186/s12885-015-1625-y
View abstract

Thorne JL, Hughes TA, Hanby AM The Molecular Pathology of Chemoresistance During the Therapeutic Response in Breast Cancer In The Molecular Pathology of Breast Cancer , 2015

Long MD, Thorne JL, Russell J, Battaglia S, Singh PK, Sucheston-Campbell LE, Campbell MJ Cooperative behavior of the nuclear receptor superfamily and its deregulation in prostate cancer Carcinogenesis 35 262-271, 2014
DOI:10.1093/carcin/bgt334
View abstract

Kim B, Hanby AM, Horgan K, Perry S, Valleley E, Verghese E, Williams B, Thorne JL, Hughes TA Neoadjuvant endocrine therapy up-regulates expression of breast cancer resistance protein, but only pre-treatment levels predict survival European Journal of Surgical Oncology 39 S78-S79, 2013
DOI:10.1016/j.ejso.2013.07.101
View abstract

Verghese ET, Drury R, Green CA, Holliday DL, Lu X, Nash C, Speirs V, Thorne JL, Thygesen HH, Zougman A, Hull MA, Hanby AM, Hughes TA MiR-26b is down-regulated in carcinoma-associated fibroblasts from ER-positive breast cancers leading to enhanced cell migration and invasion Journal of Pathology 231 388-399, 2013
DOI:10.1002/path.4248
View abstract

Kim B, Fatayer H, Hanby AM, Horgan K, Perry SL, Valleley EMA, Verghese ET, Williams BJ, Thorne JL, Hughes TA Neoadjuvant Chemotherapy Induces Expression Levels of Breast Cancer Resistance Protein That Predict Disease-Free Survival in Breast Cancer PLOS ONE 8 -, 2013
DOI:10.1371/journal.pone.0062766

Thorne JL, Ouboussad L, Lefevre PF Heterochromatin protein 1 gamma and IκB kinase alpha interdependence during tumour necrosis factor gene transcription elongation in activated macrophages. Nucleic Acids Res 40 7676-7689, 2012
DOI:10.1093/nar/gks509
View abstract

Doig CL, Singh P, Dhiman V, Thorne JL, Battablia S, Sobolewski M, Maguire O, O'Neil L, Turner BM, McCabe CJ, Campbell MJ Recruitment of NCOR1 to VDR target genes is enhanced in prostate cancer cells and associates with altered DNA methylation patterns Carcinogenesis -, 2012
DOI:10.1093/carcin/bgs331
View abstract

Thorne JL, Maguire O, Doig CL, Battaglia S, Fehr L, Sucheston LE, Heinaniemi M, O'Neill LP, McCabe CJ, Turner BM, Carlberg C, Campbell MJ Epigenetic control of a VDR-governed feed-forward loop that regulates p21 (waf1/cip1) expression and function in non-malignant prostate cells Nucleic Acids Research 39 2045-2056, 2011
DOI:10.1093/nar/gkq875
View abstract

Thorne JL, campbell M The molecular cancer biology of the VDR, in‘Vitamin D and Cancer’ In Vitamin D and Cancer , 2010
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Battaglia S, Maguire O, Thorne JL, Doig CL, Hornung L, Liu S, Sucheston L, Bianchi A, Khanim FL, Gommersall LM, Coulter HS, Rakha S, Giddings I, O'Neill LP, Cooper CS, McCabe CJ, Bunce CM, Campbell MJ Elevated NCOR1 disrupts PPAR signaling in prostate cancer and forms a targetable epigenetic lesion Carcinogenesis 31 1650-1660, 2010

Abedin SA, Thorne JL, Battaglia S, Maguire O, Hornung LB, Doherty AP, Mills IG, Campbell MJ Elevated NCOR1 disrupts a network of dietary-sensing nuclear receptors in bladder cancer cells. Carcinogenesis 30 449-456, 2009
DOI:10.1093/carcin/bgp005
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Thorne JL, Campbell MJ, Turner BM Transcription factors, chromatin and cancer The international journal of biochemistry&cell biology 41 164-175, 2009
DOI:10.1016/j.biocel.2008.08.029
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Thorne JL, Campbell MJ The vitamin D receptor in cancer The Proceedings of the Nutrition Society 67 115-127, 2008
DOI:10.1017/S0029665108006964
View abstract