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Research

CURRENT CONSORTIUMS/PROJECTS 

BREAST-PREDICT: 2013-2018

Prof. William Gallagher is currently Director of BREAST-PREDICT, which is the first Irish Cancer Society Collaborative Cancer Research Centre (CCRC) to be funded (www.breastpredict.com). This country-wide CCRC, which is supported to the level of 7.5 million euro, runs from 2013 to 2018 and involves 6 academic institutions (UCD, TCD, RCSI, DCU, NUIG and UCC), as well as the not-for-profit clinical trials organisation, the All-Ireland Co-Operative Oncology Research Group (ICORG).  BREAST-PREDICT integrates key components of several pre-existing entities in the cancer research arena in Ireland. The translational activities within the Centre owe their origins in significant part to two Science Foundation Ireland-funded programmes, namely Molecular Therapeutics for Cancer Ireland (www.mtci.ie) with Prof. Gallagher as a co-PI and Deputy Co-ordinator and Systems Biology Ireland (www.ucd.ie/sbi)  led by Prof. Walter Kolch.  Further details about the centre can be found at www.breastpredict.com.

epiCaPture: a non-invasive urine test for early detection of high-risk prostate cancer

Dr. Perry’s research team have identified a panel of loci that become specifically hypermethylated in high-grade prostate cancer (PMID: 22915211, 22906661, 17453001). They are working on translating this panel into a prognostic biomarker for early detection of high-risk prostate cancer. Prostate cancer kills approximately 300,000 men every year; early detection is vital to eradicate death from this disease. At the same time, many men live perfectly health lives with low-grade, indolent prostate cancer. For this reason, millions of men stand to benefit from a better test to identify precisely which men have the aggressive form of cancer, so that they can be treated early, whilst sparing the majority of men the significant co-morbidities associated with radical therapies.  epiCaPture, a non-invasive urine DNA methylation test which detects the presence of high-grade, potentially aggressive prostate cancer addresses this unmet need. Data on 325 men show that epiCaPture offers similar sensitivity and superior specificity compared with the current blood test used, PSA. Dr. Perry’s research is currently focused on validating these findings in a large, independent cohort. This work has been funded by an Irish Cancer Society post-doctoral fellowship award (https://www.youtube.com/watch?v=D2nDT1MyF6w ), a Movember Global Action Plan Award (https://www.youtube.com/watch?v=YA689UOFwpM), a Prostate Cancer Foundation Young Investigator Award (https://vimeo.com/44534009 ) and an SFI TIDA (A Perry).

FP7 IAPP  SYS-MEL: 2013-2017

Prof. Gallagher co-ordinates an FP7 Marie Curie Industry-Academia Partnership and Pathways (IAPP) Programme under FP7 SYS-MEL, which is focused on developing prognostic and predictive tests for melanoma, the most aggressive form of skin cancer. This programme involves 6 partners (4 academic/2 industrial) across 3 EU countries and runs from 2013-2017. This SYS-MEL Consortium is a follow-up on the successful TargetMelanoma project that was completed in June 2013.  Further details about the centre can be found at www.oncomark.com/go/research/sys-mel.

 

FASTPATH: 2011-2015

Prof. Gallagher co-ordinates an FP7 Marie Curie Industry-Academia Partnership and Pathways FAST-PATH (www.fastpathproject.com) which is focused on applying high-performance computing and automated image analysis to fast-track pathological assessment in prostate cancer.  This programme involves 6 partners (4 academic/2 industrial) across 3 EU countries and runs from 2011-2015. OncoMark Ltd  (http://www.oncomark.com/) one of the industrial partners was co-founded by Prof. Gallagher.

BUMP: Prostate Cancer Urine Biomarkers

In conjunction with Dr Jeremy Clark at the University of East Anglia (https://www.uea.ac.uk/biological-sciences/people/profile/jeremy-clark) Dr. Perry’s team is carrying out a parallel analysis of molecular changes (DNA methylation, transcriptomics) in biopsy cores and urine in an effort to assess the potential utility of urine as a “liquid biopsy” in overcoming sampling biases inherent of needle biopsies. This project is jointly funded by a cost-sharing agreement from the Royal Irish Academy and the Royal Society in the UK.

methCaP: Methylation Prostate Cancer

Cancer is driven by progressive genetic and epigenetic abnormalities, of which DNA methylation is the best characterised. Prostate cancer is a paradigm of epigenetic catastrophe; with widespread promoter hypermethylation and associated gene silencing evident early in tumour initiation and global hypomethylation appearing in later stage disease. However, the focus of research to date has centered around promoter hypermethylation and its effects on tumour suppressor genes and genes with important regulatory functions. Virtually nothing is known regarding the role of epigenetic dysregulation of regulatory genetic elements in prostate tumourigenesis. Previous research in Dr. Parry’s group laboratory found that >65% of methylation changes in primary and metastatic prostate cancers occur in intra- and inter-genic regions, beyond the remit of the promoter CpG island and transcriptional start site. Computational analysis of these regions revealed that many overlap with highly conserved vertebrate sequences, implying a functionally meaningful role. This project will characterise the role of non-conventional methylation of enhancer elements in driving aggressive prostate cancer. This project is funded by an Irish Cancer Society 2015 Postgraduate scholarship (Alexandra Tuzova).

iPROSPECT: Evolution of the CRPC epigenome and its clinical application for delivering precision medicine

This project is one of three transformative projects funded within the iPROSPECT (Irish Programme for Stratified Prostate Cancer Therapies) programme by the Irish Cancer Society & Movember. In this project, we are developing evidence-based predictive epigenetic biomarkers of response to taxane therapies and CYP17A1 inhibitor, abiraterone. We are also studying evolution of the methylome during progression to castration resistance by longitudinally sampling circulating DNA in men with late stage prostate cancer.