Clinical and Biomedical Proteomics
Our group (jointly led with Peter Selby) focuses on using proteomic-based approaches, i.e. studies examining the protein complement (proteome) of cells, tissues or fluids, to discover novel disease biomarkers or therapeutic targets. Protein quantity or form is not readily predicted from DNA/RNA due to epigenetic influences and modifications during transcription, translation and post-translationally. With most diseases having significant inter-individual heterogeneity due to involvement of multiple genes, polymorphisms and differing epigenetic influences, the analysis of multiple proteins in parallel is logical, potentially yielding highly individualised information.
Clinical proteomic studies include several cancers (renal, bladder, ovarian and cholangio carcinoma), multiple sclerosis, renal transplant rejection and Parkinson’s disease (collaboration with Phil Robinson - LIMM) with local and national clinical collaborations, and address disease-specific issues including marker discovery for diagnosis, prognosis, or response to treatment in clinical trials. Our major focus is in renal cancer where we additionally have pathway-driven projects, particularly involving the Von Hippel Lindau tumour suppressor gene. Using tissue and transfectants, we are examining genotype-phenotype correlations, determining the nature/significance of the multiple protein forms and identifying novel downstream pathways of VHL.
Technologies include 1D-and 2D-PAGE (DIGE), SELDI and LC/LC-MS/MS (iTRAQ/SILAC). Our integrated team includes people with a range of skills from research nurses through scientific lab staff to bioinformaticians and biostatisticians. Funding sources include Cancer Research UK (Cancer Clinical Proteomics Programme and a translational project grant), Department of Health, AstraZeneca, DTI and the MRC.
Figure 1 Comparison of VHL transfectants by 2D-PAGE
Figure 2 PCA plots of SELDI serum profiles from renal transplant patients and controls
Banks, R.E., Tirukonda, P., Taylor, C., Hornigold, N., Astuti, D., Cohen, D., Maher, E.R., Stanley, A.J., Harnden, P., Joyce, A., Knowles, M. and Selby, P.J. Genetic and epigenetic analysis of von Hippel Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer. Cancer Research, 66:20002011 (2006).
Munro,N.P., Cairns,D.A., Clarke,P., Rogers,M., Stanley,A.J., Barrett,J.H., Harnden,P., Thompson,D., Eardley,I., Banks,R.E. and Knowles,M.A. Urinary biomarker profiling in transitional cell carcinoma. International Journal of Cancer, 119:2642-2650 (2006).
Craven, R.A., Stanley, A.J., Hanrahan, S., Dods, J., Unwin, R., Totty, N., Harnden, P., Eardley, I., Selby, P.J., and Banks, R.E. Proteomic analysis of primary cell lines identifies protein changes present in renal cell carcinoma. Proteomics, 6:2853-2864 (2006).