Centre for Systems Medicine
Description of Organization:
The Centre for Systems Medicine at the Royal College of Surgeons in Ireland is a translational research centre of the RCSI Research Institute. Its mission is to identify genes and proteins implicated in human disease and to utilize systems biology and mathematical approaches in order to develop new prognostic tools for the treatment of cancer, neurological disorders and diabetes, and to develop more targeted therapies for patients. The Centre’s expertise lies in the transfer of in-house developed mathematical tools of apoptosis and cell survival signaling, bioenergetics and AMPK signaling, as well as ER stress and autophagy signaling into clinical settings. The competency of the Centre’s researchers is exemplified by studies employing these tools to predict response to chemotherapy for cancer patients, highlighting the significant clinical potential of systems biology-based approaches for predicting patient outcome and responsiveness to novel targeted treatment paradigms. The Centre’s computational power includes the development of ODE- and PDE-based mathematical models, Cellular Automaton approaches, as well as statistical models. The Centre provides a unique translational systems medicine platform that spans from biobanking of solid tumors (breast cancer, colorectal cancer, prostate cancer, glioblastom), genomic, genetic and clinical characterization of tumors (Sequenom analysis, RNA seq), to protein array technologies including an in-house RPPA facility for large-scale quantification of more than 150 validated signaling proteins from fresh-frozen or formalin-fixed, paraffin-embedded tissue samples. The Centre coordinates the FP7 SME-focused systems medicine and biomarker projects APO-DECIDE, ANGIO-PREDICT and OXY-SENSE (total funding: €9.5 Mio), and participates in several European and national, large-scale systems biology projects (APO-SYS, APO-COLON, MCTI). The Centre also participates in the National Biophotonics Imaging Platform Ireland (NBIP) to develop models and validate model predictions through quantitative ‘real-time’ single-cell imaging, high-content image analysis, intravital multiphoton microscopy, and small animal bioluminescence imaging.
The Centre currently hosts 9 Principal Investigators (Prehn, Rehm, Byrne, Hennessy, Huber, Hughes, Concannon, Kay, Murphy) and employs over 40 researchers with interdisciplinary skill sets ranging from biomedicine, clinical medicine (pathology, oncology), mathematics, physics and industrial IT engineering.
In kind funding provided: The Centre provides in-kind-funding in excess of €10 Mio through the provision of central infrastructure and equipment, as well as €1.5 Mio p.a. non-exchequer, institutional funding for personnel and central administration.
Recent publications relevant to the project
Davila D, Connolly NM, Bonner H, Weisová P, Dussmann H, Concannon CG, Huber HJ, Prehn JH. Two-step activation of FOXO3 by AMPK generates a coherent feed-forward loop determining excitotoxic cell fate. Cell Death Differ. 2012 Oct;19(10):1677-88.
Ebert MP, Tänzer M, Balluff B, Burgermeister E, Kretzschmar AK, Hughes DJ, Tetzner R, Lofton-Day C, Rosenberg R, Reinacher-Schick AC, Schulmann K, Tannapfel A, Hofheinz R, Röcken C, Keller G, Langer R, Specht K, Porschen R, Stöhlmacher-Williams J, Schuster T, Ströbel P, Schmid RM. TFAP2E-DKK4 and chemoresistance in colorectal cancer. N Engl J Med. 2012 Jan 5;366(1):44-53.
Hector S, Rehm M, Schmid J, Kehoe J, McCawley N, Dicker P, Murray F, McNamara D, Kay EW, Concannon CG, Huber HJ, Prehn JHM, 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 after cytochrome-c release. Mol Syst Biol. 2011 Mar 1;7:470
Watson RW, Kay EW, Smith D. Integrating biobanks: addressing the practical and ethical issues to deliver a valuable tool for cancer research. Nat Rev Cancer. 2010 Sep;10(9):646-51.