Prostate – Dublin Molecular Medicine Centre

Brief Description of Project:

Current detection strategies for prostate cancer, which shows increased incidence worldwide, are inadequate due to poor specificity. This has lead to significant dilemmas in identifying the correct therapeutic strategy, given that aggressive approaches are associated with a 30-60% risk of treatment-related side effects. We have previously established the Prostate Cancer Research Consortium (PCRC), a Dublin Molecular Medicine Centre (DMMC) flagship program which has built a shared prostate cancer bio-resource, a powerful tool for facilitating multidisciplinary trans-institutional research. The current Prostate Cancer Biomarker Discovery Program provides a focused approach to cancer biomarker discovery, evaluation and validation. This program also permits promising markers from pre-clinical exploratory studies to be evaluated. Using a comprehensive approach, the PCRC Bio-resource is interrogated with a view to identifying novel biomarker candidates. Preliminary work has (i) identified prostate cancer-specific methylation targets, (ii) allowed development of a prostate cancer-specific transcriptome array from the Bio-resource, and (iii) detected a potential proteomic signature of disease grade. The current programme aims to use proteomic approaches to identify common pathways in prostate cancer and validate lead candidates in serum and urine from prostate cancer patients. Validated candidates identified from this multi-step approach will permit guided biopsies to be performed, together with appropriate pathological and molecular analysis, providing accurate diagnostic information to inform appropriate treatment for prostate cancer patients.

Team Members and Expertise:

William WATSON, Ph.D. [william.watson@ucd.ie]
Dr. Watson is a Senior Lecturer in the School of Medicine and Medical Science, University College Dublin (UCD) and Principal Investigator at the UCD Conway Institute and Dublin Molecular Medicine Centre. He is also Lead Co-ordinator of the Cancer Biology Group in the UCD Conway Institute, which consists of 29 independent investigators. He has used transcriptomic and proteomic approaches to investigate the cellular and molecular mechanisms by which prostate cancer epithelial cell die, leading to new diagnostic tools and therapeutic targets. He is a founding member of the Prostate Cancer Research consortium and Chair of the Bio-Resource Management and Implementation group of the consortium were he has established standard operating procedures for the appropriate collection of Tissue, Blood and Urine from men undergoing radical prostatectomy.

William GALLAGHER, Ph.D. [william.gallagher@ucd.ie]
Dr. Gallagher is Associate Professor of Cancer Biology at the UCD Conway Institute. He is also Deputy Co-ordinator of the Cancer Biology Group at the Institute, and serves on the Executive Committee of the British Association for Cancer Research. His research is concerned with transcriptomic and proteomic analysis of cancer-related model systems and biopsies with a view towards biomarker discovery, as well as subsequent high-throughput validation using a combination of tissue microarrays and advanced digital slide scanning technology. He has also established comprehensive SELDI profiling and xenograft model facilities at the UCD Conway Institute that will be availed of in the current program.

Mark LAWLER, Ph.D.
Dr. Lawler is Associate Professor of Molecular Medicine at Trinity College Dublin (TCD), as well as Chief Molecular Geneticist and Director of the Cancer Molecular Genetics Laboratory at St. James's Hospital (a CPA accredited laboratory and the only cancer molecular diagnostics laboratory in Ireland). His research interests include the molecular and cellular basis of cancer, with a view to identifying new biomarkers of disease progression and response and to develop new approaches in the treatment of malignancy. He is currently Chairperson of the St. James's Hospital Cancer Strategy Group, President of the Irish Association of Cancer Research and member of the All-Ireland NCI Implementation Group. He is a founding member of the Prostate Cancer Research consortium and Chair of the Executive Management Team of the consortium.

Stephen PENNINGTON, Ph.D.
Dr. Pennington is Professor of Proteomics at the UCD Conway Institute. His research uses two-dimensional gel electrophoresis (2-DE) and LC approaches, combined with mass spectrometry, for the identification of novel markers in a range of diseases. The multi-user proteomics facility at the UCD Conway Institute now contains state-of-the-art instrumentation and software for 2-DE gel running, image analysis, spot cutting, automated protein digestion, MALDI and electrospray mass spectrometers. The facility is being used to support a series of collaborative research programmes in biomedical sciences including the Prostate Cancer Research Consortium.

Richard O'KENNEDY, Ph.D.
Dr. O'Kennedy is Professor of Biological Sciences in the School of Biotechnology at Dublin City University (DCU). He is a Principal Investigator in the PRTLI- funded National Centre for Sensor Research, the SFI-funded CSET Biomedical Diagnostics Institute and the IDA/BMS-funded Centre for BioAnalytical Sciences. He is a member of the Management Committee of the National Centre for Sensor Research at DCU and principal researcher with the Applied Biochemistry Group. He has specific expertise in the development of novel antibody- and cell-based sensor systems, antibody-based assay development, genetic methods of antibody production and novel antibody labeling systems. A number of reagents, assays, and materials developed in his laboratory have or are being successfully commercialized.

Elaine KAY, M.D.
Dr. Kay is Associate Professor of Pathology at the Royal College of Surgeons in Ireland and is a Consultant Histopathologist at Beaumont Hospital, Dublin. She is also a member of the All-Ireland NCI Implementation Group and serves on a number of medical research ethics committees. Her research is concerned with molecular pathology of a range of cancer types, including prostate, breast and bladder cancer. Her team has considerable expertise in the generation and application of tissue microarrays for biomarker validation studies. She is also using protein lysate arrays for quantitative assessment of putative biomarker expression across multiple specimens. Finally, she also is involved with William Gallagher in the application of digital slide scanning technology to fast-track biomarker validation studies.

Joe DUFFY, Ph.D., F.R.C.Path.
Dr. Duffy is Principal Biochemist at St. Vincent's University Hospital and Adjunct Professor at University College Dublin. For over 20 years, Joe Duffy has been studying genes and proteins involved in cancer metastasis and investigating these as prognostic factors in cancer. He was the first to show that a protein causally involved in experimental metastasis (i.e. uPA) was a prognostic factor in a human cancer (i.e. in breast cancer). This seminal finding has now been confirmed by at least 20 different groups worldwide. Joe Duffy is also a member of a number of international expert panels including the European Group on Tumour Markers (EGTM), The Receptor and Biomarker Group of the European Organization for Research and Treatment into Cancer (EORTC) and the PSA Isoform Review Group (UK). He currently chairs the National Academy of Clinical Biochemistry (USA) Committee for the publication of new guidelines on the clinical use of breast cancer markers.

Des HIGGINS, Ph.D.
Dr. Higgins is Professor of Bioinformatics at the UCD Conway Institute. He has a world-renowned reputation in bioinformatics from his development of the sequence alignment tool, CLUSTAL, articles based around which are some of the most cited publications in the biomedical literature. Of particular relevance to this program is the specialist expertise that his group provides in terms of analysis of gene expression and proteomic data. In particular, they have developed some highly novel approaches for integration of -omic data across technology platforms and between studies, as well as promoter mining.