Medicines Interface

Engineering insights to understand disease

med

Modern medicine increasingly considers disease in the context of a mis-functioning complex biological system. To address this complexity ChELSI interacts with medical researchers to bring an engineering approach to understanding disease.

Facilities and expertise within ChELSI provide the opportunity to bring systems-level approaches to medical research. ChELSI medical collaborations include research on stem cells, cancer, dentistry and fertility.

Embryonic Stem Cell Differentiation

The use of human embryonic stem cells for generating cell types suitable for therapy depends upon understanding the mechanisms that control cell fate into the different lineages. With the Centre for Stem Cell Biology, ChELSI has developed a new understanding of the cellular processes driving early-stage cell differentiation.

Maternal Gamete Recognition

The mammalian oviduct provides an optimal environment for gamete maturation, fertilisation and early embryonic development. With Dr Alireza Fazeli (Academic Unit of Reproductive and Developmental Medicine, Sheffield), Professor Phillip Wright's group revealed for the first time the presence of a maternal gamete recognition system that alters oviduct secretions. This significantly enhances our knowledge of fertility.

Dental Biofilms

With the School of Clinical Dentistry in Sheffield, ChELSI researchers have identified proteomic changes underpinning the persistence and immune evasion of Tannerella forsythia, a prominent bacterial cause of periodontitis (gum disease).

Pluripotency from Differentiated Cells

For regenerative medicine, and for ethical reasons, reverting differentiated cells to a pluripotent state is a desirable outcome. Through its proteomics and informatics capacities, ChELSI contributes to research revealing how differentiated epithelial cells can be reprogrammed to pluripotency.

CHELSI links to Cancer Research in Sheffield

Modern medicine increasingly considers disease in the context of a mis-functioning complex biological system. To address this complexity ChELSI interacts with medical researchers to bring an engineering approach to understanding disease.

Facilities and expertise within ChELSI provide the opportunity to bring systems-level approaches to medical research. ChELSI medical collaborations include research into cancer, stem cells, dentistry and fertility.

Specific areas of interest

Prostate cancer progression

Prostate cancer progression is unpredictable and presents a major clinical challenge. ChELSI has applied proteomic approaches, collaborating with Dr Ishtiaq Rehman and Dr Simon Cross, to compare a panel of prostate cancer cell lines including metastatic variants to uncover protein changes associated with prostate cancer progression. This study was performed alongside analysis of clinical material (serum samples) for identification of a candidate biomarker panel for prostate cancer disease progression.

Publications

Rehman I, Evans CA, Glen, A, cross SS, Eaton CL, Down J, Pesce G, Phillips JT, Ow SY, Thalmann GN, Wright PC, Hamdy FC. iTRAQ Identification of Candidate Serum Biomarkers Associated with Metastatic Progression of Human Prostate Cancer. (2012) PLoS One, Feb 15 2012

Glen A, Evans CA, Gan CS, Noirel J, Lippitt J, Eaton C, Hamdy F Wright PC and Rehman I (2010). Eight-plex iTRAQ analysis of variant metastatic human prostate cancer cells identifies candidate biomarkers – an exploratory study. The Prostate 70:1313-1332.

Evans CA, Glen A, Eaton CL, Larré S, Catto JWF, Hamdy FC, Wright PC, Rehman I (2009). Prostate cancer proteomics: The urgent need for clinically validated biomarkers. Proteomics - Clin Apps 2:197-212

Glen, A, Chee S, Hamdy FC, Eaton CL, Cross SS, Catto JWF, Wright PC and Rehman I (2008). iTRAQ-facilitated Proteomic analysis of human prostate cancer cells identifies proteins associated with progression. Journal of Proteome Research 7: 897-907

Fibre is chemopreventive in colon cancer

Fibre is chemopreventive in colon cancer and ChELSI has been collaborating with Dr Bernard Corfe to analyse the biochemical mechanisms by which is this is achieved. The work has involved protein profiling of cell lines and colon biopsy material, developing workflows for focused proteomic analysis of intermediate proteins and analysis of protein acetylation. Work has specifically been targeted to analysis of butyrate and other short chain fatty acids, to define their mode of action, including their role as potential inhibitors of histone deacetylases (HDAC) which are druggable targets in clinical trials.

Joint and associated publications

Majumdar D, Rosser R, Havard S, Lobo AJ, Wright PC, Evans CA, and Corfe BM (2012). An integrated workflow for extraction and solubilisation of intermediate filaments from colorectal biopsies for proteomic analysis. Electrophoresis 33:1967-74.

Kilner J, Waby JS, Chowdry J, Khan AQ, Noirel J, Wright PC, Corfe BM, Evans CA (2012). A proteomic analysis of differential cellular responses to the short-chain fatty acids butyrate, valerate and propionate in colon epithelial cancer cells. Mol Biosyst. 8:1146-56.

Kilner J, Corfe BM, Wilkinson SJ (2011). Modelling the microtubule: towards a better understanding of short-chain fatty acid molecular pharmacology. Mol Biosyst. 7:975-83.

Kilner J, Zhu L, Ow SY, Evans CA, Corfe BM (2011). Assessing information loss through application of the two-hit rule in iTRAQ datasets. Journal of Integrated Omics 1:124-134.

Corfe BM, Williams EA, Bury JP, Riley SA, Croucher LJ, Lai DY, Evans CA (2009). A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study. BMC Cancer 9:332-337.

Associated publications

Corfe BM (2012). Hypothesis: butyrate is not an HDAC inhibitor, but a product inhibitor of deacetylation. Mol Biosyst. 2012 8:1609-12.

Astbury SM and Corfe BM (2012). Uptake and metabolism of the short-chain fatty acid butyrate, a critical review of the literature. Curr Drug Metab. 13:815-21.

Khan AQ, Bury JP, Brown SR, Riley SA, Corfe BM (2011). Keratin 8 expression in colon cancer associates with low faecal butyrate levels. BMC Gastroenterol. 10;11:2.

Khan AQ, Shaw L, Drake PJM, Griffiths GJ, Brown SR, Corfe BM (2011). Application of high content biology demonstrates differential responses of keratin acetylation sites to short chain fatty acids and to mitosis. Journal of Integrated OMICS,1: DOI:10.5584/jiomics.v1i2.57.

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 8:28-34.

Use of saliva as a biomarker source

In patients with cancer treatment related oral mucositis (Dr Lynne Bingle, School of Dentistry), proof of concept study has been performed evaluating saliva for utility in the analysis of appetite (with Dr Bernard Corfe, and Cultech Limited).

Publications

CJ Harden, K Perez-Carrion, Z Babakordi, SF Plummer, NJ Hepburn, ME Barker, PC Wright, CA Evans & BM Corfe (2011). Evaluation of the salivary proteome as a surrogate tissue for systems biology approaches to understanding appetite. Journal of Proteomics 6:2916-2923.

Find out more about...