Chris Tselepis is a Senior Lecturer in the School for Cancer Sciences. Chris has published in excess of 40 research articles in the field of cancer, most recently focussing on the subject of iron metabolism, obesity and gastrointestinal cancer. He has received major support from the Cancer Research UK, BBSRC, WCRF, CORE and the UHB Charities.
Chris has most recently won funding through Glaxo Smith Kline to further develop his work on iron chelation and health. His work in the field of iron chelation and cancer has led to several pending patents. These iron chelation technologies are currently being optimised further through interactions with both schools of Chemistry and Chemical Engineering. In addition he is avidly working with industrial and clinical partners to deliver early phase clinical trials to assess the usefulness of iron chelators in individuals at high risk of developing colorectal cancer.
He currently supervises several clinical research fellows and his work has now expanded to assessing the role of iron in non-gastrointestinal cancers, including endocrine cancers and also assessing how obesity in the background of iron can also contribute to carcinogenesis. These more novel studies are embracing both proteomic and metabolomic technologies afforded to us through our school.
Chris is exceptionally passionate that education goes hand in hand with research and is a major contributor to Cancer Research UK/University of Birmingham outreach activity and teaches extensively on a plethora of courses within the University including MBChB, BDS, BMedSci and GEC.
Cancer Cell Biology, Cancer Prevention, Screening, Diagnosis & Survivorship, Structural Biology & Biomarkers, Diabetes, Obesity & Metabolism, Endocrine-related Cancer
Iron and Cancer
It is becoming increasingly clear that an excess of iron is associated with carcinogenesis. In particular the Tselepis group were the first to demonstrate that in the progression of both oesophageal and colorectal cancer a deregulation in a range of iron metabolism proteins. Importantly these changes culminate in increased cellular iron acquisition which in turn drives Wnt signalling; the major oncogenic signalling pathway of the intestine. This work is currently being verified in other in-vivo model systems in collaboration with Prof Sansom (Beatson Institute Glasgow). Their recent data unequivocally demonstrates that iron can indeed amplify tumour burden whilst suppression almost completely ablates its formation. Moreover, their hypothesis is that iron represents a generic carcinogen and drives all cancers and this is currently being testing in both breast cancer and also a range of endocrine cancers most notably thyroid cancer in collaboration with Prof McCabe. In addition their work is now embracing proteomic and metabolomic technologies with a view to identifying other iron stimulated pathways which impact ultimately on tumourigenesis.
Iron chelation as a platform for chemoprevention
From our ongoing studies we hypothesise that iron chelators possess potent chemopreventive properties. Thus a large aspect of the ongoing research is to identify chelators which as well as possessing potent iron chelating properties, are safe for human consumption and are non-absorbable within the gastrointestinal tract. To date several dietary agents which fulfil these criteria have been identified and these are the subject of further scrutiny, including manipulation of structure and assessing chemopreventive potential in-vivo and in-vitro model systems. In particular several of these agents are currently being worked up with a view to commencing several human clinical trials.
The role of obesity in cancer
It is clear that obesity is risk factor for developing cancer in particularly gastrointestinal cancer. However, at the molecular and cellular level how obesity influences risk is unclear. Interestingly obesity is associated with a poor functional iron status and the group is currently exploring whether this poor functional iron status is central to understanding the pathogenesis of obesity driven colorectal cancer. In addition utilising local expertise his group is also assessing which adipocyte secreted factors are important in modulating epithelial cell fate and ultimately cancer.
Cronin J, McAdam E, Danikas A, Tselepis C, Griffiths P, Baxter J, Thomas L, Manson J, Jenkins G. Epidermal growth factor receptor (EGFR) is overexpressed in high-grade dysplasia and adenocarcinoma of the esophagus and may represent a biomarker of histological progression in Barrett's esophagus. (2011) Am J Gastroenterol. 106:46-56.
Bryan RT, Tselepis C. Cadherin switching and bladder cancer. (2010) J Urol. 184:423-31.
Tselepis C, Ford SJ, McKie AT, Vogel W, Zoller H, Simpson RJ, Diaz Castro J, Iqbal TH, Ward DG. (2010) Characterization of the transition-metal-binding properties of hepcidin. Biochem J. 427:289-96.
Kroot JJ, Kemna EH, Bansal SS, Busbridge M, Campostrini N, Girelli D, Hider RC, Koliaraki V, Mamalaki A, Olbina G, Tomosugi N, Tselepis C, Ward DG, Ganz T, Hendriks JC, Swinkels DW. (2009) Results of the first international round robin for the quantification of urinary and plasma hepcidin assays: need for standardization. Haematologica. 94:1748-52.
Sharma N, Begum J, Eksteen B, Elagib A, Brookes M, Cooper BT, Tselepis C, Iqbal TH. (2009) Differential ferritin expression is associated with iron deficiency in coeliac disease. Eur J Gastroenterol Hepatol. 21:794-804.
Ward DG, Roberts K, Stonelake P, Goon P, Zampronio CG, Martin A, Johnson PJ, Iqbal T, Tselepis C. (2008) SELDI-TOF-MS determination of hepcidin in clinical samples using stable isotope labelled hepcidin as an internal standard. Proteome Sci. 6:28.
Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network. (2008) Boult JK, Tanière P, Hallissey MT, Campbell MJ, Tselepis C. Br J Cancer 98:1985-92.
Brookes MJ, Boult J, Roberts K, Cooper BT, Hotchin NA, Matthews G, Iqbal T, Tselepis C. (2008) A role for iron in Wnt signalling. Oncogene 27:966-75.