Royal College of Surgeons in Ireland
The Royal College of Surgeons in Ireland is Ireland’s largest medical school, and the RCSI Research Institute one of Ireland’s foremost translational and clinical research institution. It focuses on patient‑oriented research in oncology, metabolic and cardiovascular disorders, as well as surgical simulation and technology. The Centre for Systems Medicine (www.systemsmedicineireland.ie) at the RCSI Research Institute utilises systems biology and mathematical modelling approaches to develop new prognostic tools for the treatment of cancer, neurological disorders and diabetes, and to develop more targeted therapies for patients. Core facilities include systems modelling, dedicated clinical research centres, bio‑banking facilities, RPPA protein profiling platforms, genomics, as well as molecular, small animal and human imaging.
Role in the project:
Prof Prehn at RCSI will be involved in modelling and model integration of common and clinically important disease pathways (apoptosis, autophagy, bioenergetics). RCSI will also provide access to clinical patient samples (colorectal cancer, diabetes mellitus/metabolic syndrome, control samples), and will utilise its RPPA profiling and Sequenom platform to provide a detailed molecular characterisation of tumour and normal tissue of individual patients. RSCI and Beaumont Hospital have a quality‑assured Clinical Research Centre and associated biobanking facility, enabling tissue collection, processing, storage and distribution. Work routines and SOPs are established. All clinical and pathological information is available within the hospital and its peripheral referral centres.
Prof Prehn and the Centre for Systems Medicine are Scientific Coordinator of two SME‑focused FP7 Projects that investigate Personalised Medicine approaches in the context of cancer (APO‑DECIDE and ANGIO‑PREDICT, € 9m). Prof Prehn and the Centre for Systems Medicine also coordinate two FP7 Marie Curie Industry‑Academia Partnership Programs (OXYSENSE and ANGIOTOX, € 2.5m). Prof Prehn has been Principal Investigator on the FP7 Systems Biology APO‑SYS Integrated Project (www.APO‑SYS.eu) to develop systems biology modelling approaches of apoptosis signalling in the context of cancer and HIV (€ 11m for 21 European partners). Furthermore, Prof Prehn is institutional co‑ordinator of the National Biophotonics and Imaging Platform Ireland (NBIPI), a trans‑institutional research infrastructure program funded through the Irish Higher Education Authority (HEA) (2007‑2012; total funding to RCSI € 10m).
Profile of staff members
Prof. Prehn is the Director for the Centre of Systems Medicine and Chair of Physiology at the RCSI. Throughout his career Prof Prehn has held senior appointments at the interface of basic and clinical biomedical research. As a member of the Board of Directors of Molecular Medicine Ireland, Prof Prehn has acquired significant experience with the implementation of a translational and clinical research infrastructure in Ireland. He was a co‑applicant on the successful Wellcome Trust/HRB Clinical Research Infrastructure grant (€18 Million). Prof Prehn is an expert on apoptosis, bioenergetics and cell death signalling and has published aver 140 peer‑reviewed publications including publications in Mol Syst Biol, Nature Genetics, Proc Natl Acad Sci USAl (h‑index 42; > 5,000 citations). Prof B Hennessy is a clinical oncologist and an international leader in the application of RPPAs for quantitative protein profiling to interrogate predictive and prognostic markers in breast and colon cancer, and has established this technology at RCSI. He has published in leading clinical cancer journals (Cancer Cell, J Clin Oncol, Lancet) and is Principal Investigator of the SFI Strategic Research Centre ‘Molecular Therapeutics Centre Ireland’ (MTCI; €5.6m) Prof E Kay is a consultant histopathologist with a long standing interest in colorectal cancer and in the translation of identified biomarkers into routine diagnostic histopathology. She supervises the running of the Beaumont Hospital/RCSI tissue biobank and has published biobanking standards in leading journals such as Nat Rev Cancer.
Five recent publications relevant to the project
Hector S, Rehm M, Schmid J, Kehoe J, McCawley N, Dicker P, Murray F, McNamara D, Kay EW, Concannon CG, Huber HJ, Prehn JH. Clinical application of a systems model of apoptosis execution for the prediction of colorectal cancer therapy responses and personalisation of therapy. Gut. 2012 May;61(5):725‑33.
Huber HJ, Dussmann H, Kilbride SM, Rehm M, Prehn JH. Glucose metabolism
determines resistance of cancer cells to bioenergetic crisis Mol Syst Biol. 2011 Mar 1;7:470.
Gonzalez‑Angulo AM, Hennessy BT, Mills GB. Future of personalised medicine in oncology: a systems biology approach. J Clin Oncol. 2010 Jun ;28(16):2777‑83.
Hennessy BT, Lu Y, Gonzalez‑Angulo AM, Carey MS, Myhre S, Ju Z, Davies MA, Liu W, Coombes K, Meric‑Bernstam F, Bedrosian I, McGahren M, Agarwal R, Zhang F, Overgaard J, Alsner J, Neve RM, Kuo WL, Gray JW, Borresen‑Dale AL, Mills GB. A Technical Assessment of the Utility of Reverse Phase Protein Arrays for the Study of the Functional Proteome in Non‑microdissected Human Breast Cancers. Clin Proteomics. 2010 Dec;6(4):129‑51.
Huber HJ, Rehm M, Plchut M, Düssmann H, Prehn JH. APOPTO‑CELL‑‑a simulation tool and interactive database for analyzing cellular susceptibility to apoptosis. Bioinformatics. 2007 Mar 1;23(5):648‑50.