Cancer Proteomics Group
Overview and Core Facilities
Our major research themes are the identification of cancer biomarkers and understanding the molecular basis of carcinogenesis through the application of quantitative proteomic technologies and other molecular biology techniques. This research is funded through the Eve Appeal Gynaecological Cancer Trust, CR UK, MRC and Pancreatic Cancer UK. Facilities include a biochemistry laboratory, dedicated clean rooms for high-sensitivity, low-contamination sample handling, fluorescence 2D difference gel electrophoresis (2D-DIGE) capability, liquid-handling robotics and liquid chromatography (LC) for protein and peptide separations. Mass spectrometry (MS) instrumentation for expression profiling, protein/peptide identification and characterisation includes a Thermo LTQ Orbitrap XL hybrid mass spectrometer with on-line Dionex3000 nano-LC system and Bruker Ultraflex MALDI-TOF/TOF instrument.
Our mission also is to establish a core resource in proteomics, to provide technical expertise and knowledge in proteomic applications and data interpretation, to promote interaction between clinical and basic scientists and to provide training for the next generation of proteomics research scientists. Above all, we wish to make a difference to healthcare by addressing important questions in disease through the application of proteomic methods.
Analysis of human serum proteomes for cancer biomarker discovery
Our work aims to establish the potential of the human serum proteome for screening and ealry diagnosis of cancer in large populations and uses samples collected as part of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and in other studies. By using samples that pre-date diagnosis, we hope to identify early detection markers in the absence of non-specific late stage changes. Biomarker discovery work uses multi-dimensional protein and peptide separations linked to tandem MS with isobaric mass tagging for quantification. By comparing profiles of serum from healthy volunteers, patients with benign and malignant cancer and samples that predate diagnosis, we hope to identify biomarkers for differential diagnosis and early detection of ovarian, breast, pancreaticobiliary and colorectal cancers and endometriosis. Promising markers are being further validated in independent sample sets using immune- and MS-based assays and multi-marker models developed for translation to the clinic.
ErbB2/HER2 signalling in breast cancer
Research is aimed at identifying targets of ErbB2 and the growth factors which activate the ErbB receptor family of tyrosine kinases. Parallel differential mRNA and protein expression analyses have been applied to compare gene and protein expression profiles in model breast cancer cell lines to understand how target genes are regulated by ErbB2 overexpression and specific ErbB receptor ligands. Targets of interest are being validated and functionally characterised using cell-based assays following siRNA-mediated knockdown. Further work, applying in-depth proteomic methods for improved detection and quantification of low-abundance proteins and their post-translational modifications is aimed at understanding ErbB signalling and regulated expression at the molecular level and relating this to cellular phenotype. Methods include SILAC and multi-dimensional phospho-peptide enrichment linked to tandem MS.
Ovarian cancer biology/carcinogenesis
This research is aimed at a better understanding of the molecular events required for ovarian cell carcinogenesis, tumour progression and chemoresistance, and to thereby identify potential diagnostic, prognostic and predictive biomarkers for ovarian cancer. Work involves the application of complementary proteomic technologies to profile novel cell models of early ovarian epithelial cell transformation, metastasis, tumour suppression and chemoresistance. Candidate genes of interest are further validated and functionally characterised using RNAi-mediated knockdown and assessment of phenotype using cell-based assays.
Dr John F. Timms (Group Leader)
Dr Jenny Worthington (Research Associate)
Dr Darragh O’Brien (Postdoctoral Research Associate)
Mr Darren Thomas (PhD Student)
Ms Stella Irungu (PhD Student)
Page last modified on 22 nov 13 15:45