Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

Centre for Systems Medicine

The mission of the Centre for Systems Medicine is to provide a translational research centre which utilizes proteomics technologies to identify proteins and their modifications implicated in human disease. These approaches are used in combination with systems biology and bioinformatics approaches, in order to develop new prognostic tools for the treatment of cancer and diabetes to develop more targeted therapies for patients.

 

 CSM organogram

Research within the centre spans a range of applications including proteomics,systems biology, biomarker identification, and clinical informatics. The research fields examined within the Centre for Systems Medicine include:

Apoptosis

Colorectal Cancer

Colorectal Cancer (CRC) is the second most frequent cause of death from cancer in Ireland.5-Fluorouracil (5-FU)-based hemotherapeutic regimens are the standard treatment for these patients. Combining 5-FU with the newer chemotherapies such as oxaliplatin has improved response rates for advanced CRC to 40-50%. Resistance to chemotherapy however still limits the effectiveness of current cancer therapies. Drug resistance can be intrinsic or acquired during treatment and is believed to result in treatment failure in over 90% of patients with metastatic cancer. Furthermore, drug resistant micrometastatic tumor cells are believed to reduce the effectiveness of adjuvant chemotherapy. Therefore, overcoming drug resistance is one of the main challenges of current cancer research. Research at CHP-MSB focuses on the role of defective apoptosis signalling in tumour resistance.

Melanoma

Impaired apoptosis susceptibility is one of the key reasons for the resistance of malignant melanoma to chemo- and/or radiotherapy. So far, the understanding of apoptosis resistance or susceptibility is largely driven by descriptive and qualitative analyses of the isolated cell lines that serve as experimental models for malignant melanoma. Research at the centre aims to generate a systemic and quantitative understanding of cellular apoptosis resistance and re-sensitization of malignant melanoma.

Glioblastoma Multiforme

Research in to the induction of apoptotic cell death in glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer is another focus of the CHP-MSB. Glioblastoma cells are highly resistant to this particular form of cell death, resulting in cancer progression. In particular, the centre is interested in the role played by the Bcl-2 and IAP-families in the cell death-resistant phenotype of GBM. The overall aim of the research is to increase the susceptibility of glioblastomas to apoptosis, thereby enabling current therapies to be more effective and hence improve patient survival.

Bioenergetics

Mitochondrial Bioenergetics: Diabetes

Type 2 diabetes is a heterogeneous disorder of glucose metabolism characterized by insulin resistance, beta-cell dysfunction, and increased glucose production by the liver. According to data from the WHO and the International Diabetes Federation (IDF, 2003) there are about 150 million persons worldwide suffering from diabetes. Diabetes is rapidly increasing and expected to exceed 333 million by 2025 making diabetes fated to become one of the world most important and costly diseases. Current therapies fail to address the underlying pathophysiology of diabetes, and consequently fail to restore normal control of glucose metabolism. Work at the centre aims to further our understanding of factors controlling beta-cell mass regulation and beta cell apoptosis, with the hope of identifying drug targets that can be further developed for therapeutical intervention

Biomarker Discovery: Colorectal Cancer

There is sufficient clinical evidence that the key to decreasing colorectal cancer (CRC) related mortality is early diagnosis through effective screening. A primary focus of the CHP-MSB is the development of a CRC specific diagnostic test which will increase early detection which is necessary to prioritise those patients in need for colonoscopy, and to decrease the morbidity and mortality from this disease. The centre aims to clinically validate a minimally invasive, inexpensive, CRC specific serum diagnostic test based on the presence of specific tumour-associated antigens that we have identified in previous work. Our aim is to deliver a serum-based, non-invasive test that can be performed in routine clinical laboratories and will aid in the stratification of patients for colonoscopy. We believe that the development of such a test has the potential to greatly impact on the delivery and quality of clinical services in Ireland and elsewhere. Furthermore, through appropriate future commercialisation, the current clinical project has the potential to increase the capacity of Ireland as a knowledge-based economy.

Angio-tox

AngioTox is an EU FP7-funded IAPP project integrating expertise in biomarker discovery, histopathology, multi-modality in vivo imaging and automated image analysis.The AngioTox Consortium was established in 2010 to mechanistically assess the toxicities associated with the use of angiogenesis inhibitors for the treatment of cancer. The ultimate goal of this consortium is to identify an AngioTox Safety Panel of toxicologic markers to facilitate improved screening of angiogenesis inhibitor toxicologic parameters, inform clinical drug dosing regimens, facilitate the development of more specific and potent angiogenesis inhibitors and significantly improve patient care.

The CSM is generously supported through funding awards from both National and International sources as well as our Industry partners. Furthermore this program is supported by the Principal Investigators and the core facilities provided by the centre.