Research

Research at the Discipline of Surgery provides a facility for medical students and surgical personnel wishing to undertake:

• Laboratory based Research
• Education Based Research
• Clinical Practice

Current research areas include Breast Cancer, Gastrointestinal/Colorectal cancer, Orthopaedics and Vascular Surgery as well as clinical and surgical teaching based studies. The research laboratory is also home to full-time scientific cancer researchers

Research is conducted in collaboration with the following national and international institutions

• The Mayo Clinic, Minnesota, USA
• Yale University, Connecticut USA
• Baylor College of Medicine, Texas, USA
• University of Arizona, USA
• Nottingham Trent University, UK
• Biomedical Diagnostics Institute (BDI), DCU, Dublin
• All Ireland Cooperative Oncology Research Group (ICORG), Dublin
• Regenerative Medicine Institute (REMEDI), NUI Galway
• National Centre for Biomedical Engineering Science (NCBES), NUI Galway
• School of Natural Sciences, NUI Galway
• School of Physics, NUI Galway

Cancer Research Projects

Molecular Profiling of Breast and Colon Cancer: mRNA and microRNA expression

The goal of molecular profiling is to better understand the molecular anatomy of normal cells and cells in various stages of disease so that new treatments and diagnostic tests may be specifically developed. By profiling what genes that are expressed or not expressed and characterising whether these patterns of gene expression are aberrant or characteristic of disease sub-type or clinical features we hope to better understand the complex molecular mechanisms underpinning breast cancer aetiology and progression. To carry out these studies we correlate the patterns of gene expression from patient samples with clinical follow-up data.

MicroRNAs ( miRNAs) are non-coding regulatory genetic elements expressed in a tissue-specific and developmentally regulated manner. Their expression has been implicated in critical biological processes including development, cell differentiation and oncogenesis. miRNAs have the ability to regulate activity of other genes. Recent findings have demonstrated that miRNA expression is frequently abnormal in breast cancer. We are currently investigating the hypothesis that that miRNAs are key regulators of cancer metastasis and progression and could act as novel biomarkers to improve cancer diagnosis and prognostication. miRNA realtime PCR is currently being used to investigate the expression profiles of cancer-associated miRNAs in fresh frozen, paraffin embedded tissue and peripheral blood.

MicroRNA expression profiling has been performed using Taqman Low Density Arrays in colorectal tumours to identify signatures that predict disease aggressiveness, risk of recurrence and response to adjuvant therapy. Aberrantly expressed miRNAs are validated by real-time PCR. To further elucidate the miRNA-mRNA regulatory mechanisms, expression of potential gene and downstream protein targets of dysregulated miRNAs are investigated by PCR and immunohistochemistry.

Our researchers are involved in an ICORG Translational Clinical Trial investigating circulating miRNA (ICORG 10-11). This is in conjunction with other regional hospitals in Ireland.

(Collaborators: Yale University, USA; Nottingham Trent University, UK; Baylor College of Medicine, USA; ICORG; School of Natural Sciences, NUI Galway)

Mesenchymal Stem Cells and Breast Cancer

Adult Mesenchymal Stem Cells (MSCs) have the proven ability to specifically home to the site of tumours and their metastases, and also appear to bypass the host immune system. As a result of these remarkable traits, research is ongoing to determine the potential of these cells for tumour-targeted delivery of therapeutic genes. Further understanding the biology of MSCs and their interactions with breast cancer cells will be fundamental to determining whether these cells can be safely harnessed for tumour-targeted delivery of therapeutic agents. There are two central aims of the Breast Cancer- MSC program

1. To investigate the potential of MSCs for tumour targeted delivery of therapeutic genes in the setting of metastatic breast cancer
2. To understand the prevalence, role and fate of native MSCs in the primary breast tumour microenvironment

(Collaborators: REMEDI; Mayo Clinic, USA; University of Arizona, USA)

Tumour Microenvironment in Breast Cancer

It is well established that within the breast tumour microenvironment, neoplastic epithelial cells coexist with stromal fibroblasts. Stromal cells are not simply innocent bystanders at breast cancer sites and studies have shown that they possess a striking tumour promoting property as distinct from normal stromal cells. This is mediated partly through secretion of signalling factors, such as chemokines, that direct malignant epithelial cell function. The precise functional contributions of stromal cells or these signalling factors to carcinoma growth and progression remain poorly understood. Current studies in the laboratory aim to elucidate mechanisms of action of stromal cells within the primary tumour microenvironment, identifying factors secreted and their impact on epithelial cell gene expression and function.

Breast Cancer Population Genetics

To better understand the underlying causes of breast cancer we currently involved in a large collaborative study to investigate the hereditary component to breast cancer in the west of Ireland population in patients with a family history of the disease. Among the Irish breast cancer population there are many women with a significant family history of breast cancer who do not carry germline mutations in either of the 2 breast cancer susceptibility genes: BRCA1 and BRCA2 mutations by current diagnostic methods. For these women and their families risk analysis and heritability calculations remain elusive. It is thought that several common low penetrance genes account for the non- BRCA associated genetic susceptibility to breast cancer. These genes are likely to be inherited not as autosomal dominant traits or their penetrance would be obvious; but as complex traits that need to interact with each other and with the environment to induce their cancer causing effects. In order to identify these genes we are performing an association study to compare DNA from 1000 breast cancer patients in the West of Ireland with 1000 matched controls from the same ethnic and regional background.

(In collaboration with University of Oxford, UK; Breast Cancer Association Consortium)

Circulating miRNA Biochip for Diagnosis & Prognosis of Breast Cancer

In November 2010 the Biomedical Diagnostics Institute (BDI) launched its new research programme, 2010-2015, supported by €19 million investment by Science Foundation Ireland. One of the Clinical Oncology projects, entitled " benefitting from this investment is being carried out by our breast cancer researchers. This project involves the development of a biochip platform (free of molecular amplification) around a panel of miRNA-based breast cancer biomarkers. 

(In collaboration with NCBES and Dublin City University)

Other Research

microRNAs in metabolic syndromes (Helen Heneghan) 

Quality of Life Study & Economics of Cancer Management (Helen Heneghan in collaboration with Ciaran O'Neill, Economics, NUI Galway)

Research output/Bibliometrics (Ronan Glynn)

Efficacy of a cognitive-behavioural intervention for women with recently diagnosed breast cancer: a randomised control trial
(In collaboration with the School of Psychology, NUI Galway)

Research Methods

Single Nucleotide Polymorphism (SNP) Genotyping

Therapeutic Gene Delivery & Imaging 

Primary Tissue Culture

Cell proliferation, migration and transfection assays

mRNA and miRNA expression profiling by Real Time Quantitative PCR (RQ-PCR)

Immunological Assays