The University of Sheffield
Department of Oncology

Dr Bernard M Corfe BSc PhD

Molecular Gastroenterology Research GroupDr Bernard Corfe
Academic Unit of Surgical Oncology
Department of Oncology
The Medical School
Beech Hill Road
Sheffield
S10 2RX
UK

Office: GU28

Tel: +44 (0)114 271 3004
Fax: +44 (0)114 271 3314
Email: b.m.corfe@sheffield.ac.uk

Secretary: Laura Haslam: +44 (0)114 226 1229

Biography

I joined the University of Sheffield as a lecturer in 2002 following training in molecular pharmacology.

My research training was in microbial molecular biology and my first postdoc was in Sheffield with Professor Anne Moir in the Department of Molecular Biology and Biotechnology. I subsequently worked with Professor Caroline Dive in Manchester, studying the regulation of apoptosis in response to chemotherapeutic drugs. It was through this research that I became interested in the regulation of apoptosis by butyrate.

Research Interests

Work in my group examines the relationship between diet, short-chain fatty acid production and metabolism and cell fate in the normal and neoplastic colon. A detailed summary is found on my Research Page.

Butyrate and cell fate determination: Butyrate is of particular interest as it is described as an inhibitor of histone deacetylases – although we disagree with this (Corfe, 2012), is in clinical trials or clinical use, yet it is also a fermentation product of the gut microbiome present at pharmacologically active concentrations in the normal healthy colon lumen. It has been implicated as a mechanism for cancer prevention by fibre. HDACs do not solely deacetylate histones and a growing literature recognises protein acetylation as a regulatory mechanism comparable with phosphorylation. My group studies the transcription factor Sp1 (Chirakkal et al., 2006; Waby et al., 2010, Yu et al., 2010) and the cytoskeletal proteins keratin 8, 18 and 19 (Leech et al., 2008; Drake et al., 2009; Khan et al., 2011; Majumdar et al., 2012) all of whose functions are controlled, inter alia, by acetylation.

Short-chain fatty acid metabolism: We are currently working on the relationship between production of acetyl-coA (the substrate for protein acetylation) and acetylation of metabolic enzymes involved in its production. Differences between the management and effects of SCFA are a particular interest (Kilner et al., 2012; Astbury & Corfe 2012)). We use a combination of systems biology and protemics for this work.

Crypt cell fate modelling: We have noted changes in the composition of cell types in the colon crypt in response to butyrate and to neoplasia (Yu et al., 2011) and we are developing fully semantic models to examine crypt cell fate determination (Smallbone and Corfe, submitted).

Organ level modelling: I am increasingly interested in the concept of field cancerization as applied to the colon and an ongoing study using proteomic approaches is revealing multiple proteins and pathways that are altered in the normal tissues around fields (Corfe et al., 2009) has led us to propose testable qualitative models to axamine mechanisms of field cancerization (Rosser et al, submitted). Modelling approaches are being trialled in collaboration with Professor Steve Billings, Yifan Zhao and Hualiang Wang (ACSE) and Kieran Smallbone (MCISB).

Diet-Microbiome Interactions, Functional analysis of Probiotics: I am sceptical about the centrality of fibre as a determinant of SCFA concentrations (Williams et al., submitted). We have initiated a programme of studies to generate a complete detailed description of the diet, microbiome and luminal metabolome in steady state and in response to probiotics. This is done in collaboration with Julian Marchesi (Cardiff), Sue Plummer and Iveta Garaiova (Obsidian Ltd). We are using a non-linear approach to assess which factors are important and which factors interact in the production of SCFA, in collaboration with Professor Stephen Billings (Automated Control and Systems Engineering).

Interface with Humanities: Gastrointestinal conditions often get reported late or at an advanced state due to stigmatisation of GI functions by society. Irritable Bowel Syndrome in particular is an often-debilitating . We are collaborating with Vicky Grant and Brendan Stone (English) to develop narratives around IBS. We have explored social media and its conflict with peer-reviewed literature within a framework of discourse theory (Sprake et al., 2012). We are interested in the philosophy of systems biology and the scientists relationship with hypothesis rejection (Evans & Corfe, submitted; Corfe, 2012; Blog: scientist or icoloclast?).

Teaching Interests

I am a member of the Bioinfomatics Trainers Network.

I jointly deliver the bioinformatics components of the cross-Faculty DDP in Proteomics-Informatics.

I organised a cross-Faculty training session in Metabolomics Cheminformatics.

I collaborate with EBI to deliver bioinformatics training through learned societies.

I lead the Literature Review Module in the MMedSci in Human Nutrition.

I developed and led the Research Skills Module (in 2011), the Molecular Nutrition Module (in 2008), and the Literature Review Module (in 2010) and the Clinical Nutrition Module (in 2002) in the MMedSci in Human Nutrition.

Professional Activities

Editorial Board Member for Molecular Physiology and Cell Signalling, European Journal of Nutrition.

Scientific Theme Leader, Cellular and Molecular Nutrition, Nutrition Society.

Member of the Training and Education Committee, Nutrition Society.

Associate Editor, International Journal of Experimental Pathology.

Associate Editor, Journal of Integrated OMICS.

Associate Editor, Nutrition & Cancer.

Review Editorial Board, Frontiers in Vascular Physiology.

Member, European Network for GastroIntestinal Health Research.

Consulted for: INSERM, Norgine Ltd.

Manuscript reviewer for: Gut, Oncogene, Journal of Proteome Research, American Journal of Physiology, FEMS Microbiology Ecology, British Journal of Pharmacology, Nutrition and Cancer, Diversity, Clinical Biochemistry, Clinical and Experimental Immunology, Cell Death and Differentiation, Nutrition Journal, British Journal of Cancer, International Journal of Cancer.

Grant reviewer for: BBSRC, MRC, AICR, Tenovus, WCRF.

Current Projects

See also my group website:

http:/www.shef.ac.uk/oncology/units/surgicaloncology/research/gastro_group

EPSRC PhD Studentship. Systems modelling of the effect of short-chain fatty acids on tubulin isoforms and cytoskeletal integrity. Steve Wilkinson [PI], Bernard Corfe.

Bardhan Research and Education Trust. Expression and acetylation of keratins 8 and 18 in colonic mucosa of patients with Ulcerative Colitis: role in pathogenesis of colitis-associated colorectal neoplasia and dysplasia. Alan Lobo [PI], Bernard Corfe, Debrata Majumdar - £22,000.

Obsidian Ltd/Welsh Assembly/Cardiff University: Metagenomic analysis of alteration in gut microflora in response to probiotics.

Key Publications (all papers from the current year, plus highlights from previous years)

2013

Corfe BM, Kilner J, Chowdry J, Roderick SP, Benson RSP, Griffiths GJ & Evans CA Application of High Content Biology to Yield Quantitative Spatial Proteomic Information on Protein Acetylations. Methods in Molecular Biology, in press.

Evans CA, Griffiths JR, Unwin RD, Whetton AD, Corfe BM Application of the MIDAS approach for analysis of lysine acetylation sites. Methods in Molecular Biology, in press.

Evans CA, Ow SY, Smith DL, Corfe BM, Wright PC Application of a CIRAD approach to discovery of lysine acetylation sites. Methods in Molecular Biology, in press.

Mackinder M, Evans CA, Chowdry J, Staton CA & Corfe BM Alteration in intermediate filament profile with increasing metastatic potential in breast cancer cells. Cancer Biomarkers, minor revision requested.

Williams EA, Lai DY, Bury JP, Riley SA, Plummer S, Mrchesi JR & Corfe BM Cross-sectional analyses show no association between fibre intake and faecal butyrate level. Eur J Nutr, in revision.

Evans CA & Corfe BM Are proteins a redundant ontology? Epistemic limitations and strategies for analysis of multistate species. Molecular Biosystems, submitted.

Stephens M & Corfe BM Nutritional bioinformatics: where are we going and how far have we got? Eur J Nutr, submitted.

Smallbone K & Corfe BM A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types. Int J Exp Pathol, submitted.

Rosser R, Chapple, K & Corfe BM Models for field effects in metachronous colorectal adenoma. Int J Exp Pathol, submitted.

Kilner J, Waby JS, Chowdry J, Wright PC, Corfe BM & Evans CA "Use of proteomic approaches to identify differences in cellular response to butyrate, valerate and propionate in colon epithelial cells". Molecular Biosystems, in press, DOI:10.1039/C1MB05219E.

Harden CJ, Perez-Carrion K, Babakordi Z, Plummer SF, Hepburn N, Barker ME, Wright PC, Evans CA & Corfe BM Evaluation of the salivary proteome as a surrogate tissue for systems biology approaches to understanding appetite. J Proteomics, in print.

Harden C, Richardson JC, Dettmar PW, Corfe BM & Paxman JR An ionic gelling alginate formulation attenuates postprandial glycaemia in male subjects. J Functional Foods, in print.

Harden C, Maya Jiminez T, Jones A, Barker ME, Hepburn NH, Garaiova I, Plummer S & Corfe BM Use of an in vitro screen to identify long chain fatty acids triggering optimal CCK release and impact of Long chain fatty acids on 24-hr energy intake in healthy males. Br J Nutrition, in print.

Astbury SM & Corfe BM Uptake and metabolism of butyrate – gaps in current understanding. Current Drug Metabolism, in print.

Corfe BM Hypothesis: butyrate is not an HDAC inhibitor but a product inhibitor of deacetylation. Molecular Biosystems, in print.

Majumdar D, Rosser R, Havard S, Lobo A, Evans CA & Corfe BM Fractionation, extraction and solubilisation of intermediate filaments from colorectal biopsies for proteomic analysis: description and validation of a technique. Electrophoresis, in print.

Benefer M, Corfe BM, Russell JM, Short R & Barker ME Water intake and post-exercise cognitive performance: an observational study of long distance walkers and runners. Eur J Nutr, in print.

Majumdar D, Tiernan JP, Evans CA, Lobo A & Corfe BM Roles of keratins in colorrectal epithelial function and disease. Int J Exp Pathol, in print.

Sprake EF, Grant VA & Corfe BM Systematic Qualitative Analysis of Anecdotal Data provides Evidence for a Role of Vitamin D in Irritable Bowel Syndrome. British Medical Journal Case Reports, in press.

Lee ES, Corfe BM & Powers HJ "Development and characterization of lumiflavin-based intestinal models of riboflavin depletion: effects on redox, proliferation and viability". Eur J Nutrition, in press.

Selected papers pre-2012

Yu DCW, Bury JP, Tiernan J, Waby JS, Staton CA & Corfe BM (2011) Interaction between butyrate level and field effects in the regulation of enteroendocrine cell number and neuropilin expression in the human colon. Molecular Cancer 10:27. This paper has achieved Highly Accessed status.

Williams EA, Nai XL & Corfe BM Dietary intakes in subjects with irritable bowel syndrome. BMC Gastroenterology 11:9. This paper has achieved Highly Accessed status.

Waby JS, Chirakkal H, Yu CW, Griffiths GJ, Benson RSP, Bingle CD & Corfe BM (2010) Sp1 acetylation results in loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line. Molecular Cancer 9: 275.

Yu CW, Waby JS, Chirakkal H, Staton CA & Corfe BM (2010) Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation. Molecular Cancer 9:276.

Drake PJM, Griffiths GJ, Benson RP & Corfe BM (2009) Application of high-content analysis to the study of post-translational modifications of the cytoskeleton. Journal of Proteome Research 8(1):28-34.

Leech SH, Evans CA, Shaw L, Wong CH, Connolly J, Griffiths JR, Whetton AD & Corfe BM (2008) Proteomic analyses of intermediate filaments reveals cytokeratin 8 is highly acetylated – implications for colorectal epithelial homeostasis. Proteomics 8: 279-288.

Chirakkal H, Leech SH, Brookes KE, Prais AL, Waby JS & Corfe BM (2006) Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding. Oncogene 25: 7192-200.

Makin GWJ, Corfe BM, Griffiths GJ, Hickman JA & Dive C (2001) Drug-induced changes in Bax conformation and processing: differences between drug sensitive and resistant cells occur after exposure of its N-terminus. EMBO Journal 20: 6306-6315.

Griffiths GJ, Corfe BM, Savory P, Hickman JA & Dive C (2001) Activation of the pro-apoptotic protein Bak by damage signals in T-lymphoma cells: a two-step process with changes at the N-terminus and BH-1 domain. Oncogene 20: 7668-7676.

Corfe BM, Dive C & Garrod DR (2000) Changes in intercellular junctions during apoptosis precede nuclear condensation or phosphatidylserine exposure on the cell surface. Cell Death and Differentiation 7: 234-235.

Griffiths GJ, Dubrez L, Morgan CP, Jones NA, Whitehouse J, Corfe BM, Dive C & Hickman JA (1999) Cell damage-induced conformational changes of the pro-apoptotic protein bak in vivo precede the onset of apoptosis. Journal of Cell Biology 144: 903-914.

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