Principal Investigator Profile

Professor Michael Kerin

Biography

Professor Kerin is Professor of Surgery at NUI Galway and Director of the National Breast Cancer Research Institute.  He qualified in Medicine from University College Galway in 1984 and spent the following five years at University College Hospital including one year working full-time in the area of breast cancer research under the directorship of Professor Fred Given.  He completed basic surgical training and a thesis on estrogen receptor gene in the laboratory of Professor Frank Gannon.  He then spent two years working as Registrar in Leeds before completing higher surgical training in Ireland.  He then spent three years working as Senior Lecturer and Honorary Consultant Surgeon at the University of Hull in Yorkshire before taking a position as Lead Surgeon with the National Breast Screening Programme, BreastCheck at the Mater Hospital in Dublin in 1999.  Professor Kerin was working as a Principal Investigator and Senior Lecturer at the Conway Institute.  He took up his professorial post at NUI Galway in 2004 and has developed a clinical research programme which focuses on breast cancer research. 

Professor Kerin has a track record in research on endocrine response in breast cancer since doing his thesis on RFLPs in oestrogen receptor gene and has published widely on ER-beta. He also has a long term interest in molecular biology of breast cancer and has published on comparative genomic hybridisation, tumour markers (especially CA15-3), vascular endothelial growth factor, telomerase activity and cytokines. He has supervised several undergraduate and postgraduate research projects and his students have won a range of prizes including the Party Prize (Society of Surgical Research) on two occasions, the Bennett Medal (Trinity College), the President’s Prize (Royal Academy of Medicine in Ireland) and the Freyer Memorial Medal (NUIG). He has published more than 100 papers in peer-reviewed journals.  His current position involves delivery of clinical care especially for patients with breast cancer.   He is a former James IV Traveller, Millin Lecturer RCSI, Robert Smith Lecturer at Association of Surgeons and is currently a board member of Health Research Board and Council Member of RCSI. 

Link to own Web page: http://www.nuigalway.ie/surgery

Research Area:

• Gene Expression Profiling investigating the metastatic potential of early breast cancer using a combined gene expression microarray and real-time quantitative PCR approach
• Gene Therapy investigating the potential of human mesenchymal stem cells as vectors for therapaeutic gene delivery to breast tumours
• Population Genetics to identify common genes that predispose to breast cancer.

Current Projects:

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

As part of an ongoing HRB-funded departmental project entitled "Gene expression profiling to predict response to tamoxifen treatment in axillary node-negative breast cancer patients" , mRNA derived from early-stage breast cancer patients has been hybridised to whole genome expression arrays. The purpose of this study is to develop a new predictive tool that will have clinical utility in tailoring treatment options for axillary node negative breast cancer patients and out-perform currently available predictive markers. To do this breast tumour samples from patients with early stage breast carcinomas, treated with the anti-oestrogenic agent tamoxifen, have been divided into good prognosis and poor prognosis groups based on patient 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. In 2007 researchers were awarded a Health Research Board grant for the study of microRNAs in breast cancer.

(In collaboration with Dr. Vladimir Benes, European Molecular Biology Laboratory, Heidelberg and the NCBES, NUI Galway)

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.

Gene Therapy & Mesencymal Stem Cells in Breast Cancer and Bone Metastasis

A variety of gene therapy strategies have been developed and evaluated for breast cancer treatment but clinical responses remain poor. One of the major barriers to effective therapeutic results is degradation of adenoviral constructs by the host immune system. The use of mesenchymal stems cells (MSCs) as systemic delivery vehicles for therapeutic genes has been proposed as a method to overcome this as a result of their combined ability to home to the tumour site, and evade transduced human MSCs to breast cancer primary cultures and cell lines both in vitro and in vivo, and to identify factors mediating this migration. Although the migratory behaviour of MSCs has been investigated , the signals that mediate migration to specific targets are unknown. The ability of transduced MSCs to deliver therapeutic agents is also being investigated. In 2007 and 2008 researchers were awarded Health Research Board and Cancer Research Ireland grants, respectively, for these research studies.

(In collaboration with REMEDI, NUI Galway and Professor John Morris , Mayo Clinic College of Medicine, Rochester, 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 Professor Ian Tomlinson et al., Cancer Research UK)

Other Breast Cancer Projects

The effect of hysterectomy on serum VEGF levels in pre and postmenopausal patients

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

International collaborations include Prof. John Morris (Mayo Clinic), Prof. Ian Tomlinson at Cancer Research UK and Dr. Vladimir Beneš, EMBL, Heidelberg and nationally with the Conway Institute, TCD as well as local breast cancer collaborations with Prof. Grace Callagy, Professors Tim O’Brien, Frank Barry, Peter Dockery and Dr. Howard Fearnhead. Currently 2 post-doctoral research fellows, 2 senior technicians and 8 MD/PhD students are employed on the above projects. We are currently in receipt of grant funding totalling in excess of €1.3 million and have successfully published several peer reviewed manuscripts based on work conducted in this laboratory.

List of Publications:

Molloy AP, Martin FP, Dwyer RM, Griffin TP, Murphy JM, Barry FP, O’Brien T and Kerin MJ.
Mesenchymal stem cell secretion of chemokines during differentiation into osteoblasts, and their potential role in mediating interactions with breast cancer cells
Int J Cancer 2009 124, 326–332

McInerney N, Colleran G, Rowan A, Walther A, Barclay E, Spain S, Jones AM, Tuohy S, Curran C, Miller N, Kerin M, Tomlinson I, Sawyer E.  Low penetrance breast cancer predisposition SNPs are site specific. Breast Cancer Res Treat. 2008 Nov 13. [Epub ahead of print]

Lowery AJ, Sweeney KJ, Molloy AP, Hennessy E, Curran C, Kerin MJ.  The effect of menopause and hysterectomy on systemic vascular endothelial growth factor in women undergoing surgery for breast cancer
BMC Cancer. 2008 Sep 30;8(1):279

Davoren PA, McNeill RE, Lowery AJ, Kerin MJ, Miller N.  Identification of suitable endogenous control genes for microRNA gene expression analysis in human breast cancer.  BMC Mol Biol. 2008 Aug 21;9:76

Potter SM, Dwyer RM, Curran CE, Hennessy E, Harrington KA, Griffin DG, Kerin MJ.  Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones.  Breast Cancer Res Treat. 2008 Jun 4. [Epub ahead of print]

Ní Mhuircheartaigh J, Curran C, Hennessy E, Kerin MJ.Prospective matched-pair comparison of outcome after treatment for lobular and ductal breast carcinoma.
Br J Surg. 2008 Jul;95(7):827-33

Lowery, AJ, N Miller, RE McNeill and MJ Kerin.
MicroRNAs as Prognostic Indicators and Therapeutic Targets: Potential Effect on Breast Cancer Management.
Clin Cancer Res 2008 14(2): 360-5.

Bretschneider N, Brand H, Miller N, Lowery AJ, Kerin MJ, Gannon F, Denger S.
Estrogen induces repression of the breast cancer and salivary gland expression gene in an estrogen receptor alpha-dependent manner.
Cancer Res. 2008 Jan 1;68(1):106-14.

McNeill RE, Miller N, Kerin MJ.  Evaluation and validation of candidate endogenous control genes for real-time quantitative PCR studies of breast cancer.
BMC Mol Biol. 2007 Nov 27;8:107

Dwyer RM, Potter SM, Harrington KA, Lowery AJ, Hennessy E, Murphy JM, Barry FP, O'Brien T, Kerin MJ.  Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells.
Clin Cancer Res. 2007 Sep 1;13(17):5020-7

Sweeney KJ, Boland PJ, King T.
The management of asymptomatic skeletal breast cancer: a paradigm shift.
Ann Surg Oncol. 2007 Sep;14(9):2430-1.

Sweeney KJ, Sacchini V.
MRI evaluation of breast cancer.
N Engl J Med. 2007 Jul 12;357(2):192;

McNeill, RE. 
Real-time PCR in clinical applications.
Genome Technology 2007 July/August.

Sweeney KJ, Ryan E, Canney M, O'Daly BJ, Kerin MJ.  Justifying adjuvant chemotherapy in breast cancer: A survey of women and healthcare professionals.
Eur J Surg Oncol. 2007 Jan 29

Manning AT, Garvin JT, Shahbazi RI, Miller N, McNeill RE, Kerin MJ
Molecular profiling techniques and bioinformatics in cancer research.
Eur J Surg Oncol. 2007 Apr;33(3):255-65. Review.

Manning AT, O'Brien N, Kerin MJ.
Roles for the calcium sensing receptor in primary and metastatic cancer.
Eur J Surg Oncol. 2006 Sep;32(7):693-7. Review.

Books/Chapters

A Guide to Breast Surgery.
O'Brien N and MJ Kerin.
Haslemere, Surrey,
Euromed Communications Ltd., 2005.

Disorders of the Breast in Clinical Surgery, 2nd Edition
Kerin MJ.
Blackwell Science, Oxford, U.K., 2003

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