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Trinity College Dublin

Personal Information
Name Sheils, Orla
Main Department Histopathology
College Title Professor
E-mail osheils@tcd.ie
College Tel +353 1 896 3284
Web http://people.tcd.ie/osheils
Fax +353 1 896 3285
 
Biography
I studied Biomedical Science and was appointed research scientist at TCD following undergraduate study. My appointment was in the academic department of Histopathology, where my remit was to develop translational research. I was seconded to the Department of Genetics and on return to Histopathology I established a molecular pathology laboratory affiliated to the academic Department of Histopathology at St James’ Hospital (one of the University’s main teaching hospitals). I currently head a research group based at the Institute of Molecular Medicine in TCD’s Health Sciences Centre at St James’ Hospital, with a satellite group in the Coombe Women’s Hospital. I am involved with undergraduate and postgraduate teaching and have an active research portfolio. My PhD thesis examined molecular aspects of thyroid neoplasia. Following its completion I expanded this area of research and molecular endocrine pathology (emphasis on thyroid) remains one of the Department’s core areas. Other core areas include cancers of the cervix, ovary, prostate and head & neck. My group also has an active interest in the molecular pathobiology of Inflammatory Bowel Diseases Translational research remains a common theme throughout linking identification of disease processes with targets for early disease detection or classification. My group works closely with a number of biotech companies including Applied Biosystems, Affymetrix, DAKO and NorChip. I am currently reading for a Masters degree in Medical Law and Bioethics and I sit on the College’s Ethics Committee.
 
Representations
Details Date
Member, MMI Cancer Principal Investigators, Trans-institutional grouping of Principal Investigators leading research on Cancer themes
Member, Core Technology PI's, DMMC Principal Investigators leading the development of core technology platforms.
 
Membership of Professional Institutions, Associations, Societies
Details Date From Date To
Member of Coombe Women’s Hospital ‘Hospital Research Committee 2006 present
Member of the Ethics Working Group Royal College of Physicians of Ireland 2005 present
Member of the Pathological Society of Great Britain and Ireland 2001 present
Member of Medico-legal Society of Ireland 2006 present
Member of Editorial board of Journal of Endocrine Pathology 2009
 
Awards and Honours
Award Date
FTCD 2009
Provost's Teaching Award 2012
 
Languages
Language Skill Reading Skill Writing Skill Speaking
English Fluent Fluent Fluent
 
Description of Research Interests
I have been an independent investigator since 2001 and the underlying theme of my research is to understand the causes and molecular basis of the development of disease, with particular reference to cancer, and to apply this knowledge to improving disease prevention, detection, diagnosis and treatment. Improving the outlook for cancer patients can only come from an understanding of molecular and cell biology. There has been a dramatic increase in knowledge of the molecular genetics of cancers over the last few years and already we have reached the point where this can be translated into clinical application. With increased understanding of the mechanics of disease progression comes a requirement for innovative methods to detect nuances of patient specific tumours to triage those most likely to benefit from particular chemotherapeutic approaches and to discriminate between individual prognostic outcomes. Translational research remains a common theme throughout my research, linking identification of disease processes with targets for early disease detection or classification. I chair the TCD Faculty of Health Sciences Research Ethics Committee and provide legal and ethics advice within the department and to other researchers embarking on research projects. I have been responsible for the procurement of grants valued in excess of €30M during this time from national funding agencies such as S.F.I., EU, HRB, ICS and HEA in addition to the Meath Foundation and the Emer Casey Foundation. I have also been fortunate in securing industrial support from Life technologies (Applied Biosystems/Ambion/Invitrogen), Affymetrix, Vysis., Johnson & Johnson, Merck-Serono and Amgen.
 
Research Interests
Autoimmunity Bioinformatics Biomedical ethics Cancer genetics and cell biology including metastasis
Cervical cancer Commercialisation of scientific research Diagnostics Endocrine function and disease
Environmental Carcinogenesis Foetal, maternal and neonatal physiology Gene transcription in human cancer Gynaecology oncology
HASHIMOTO THYROIDITIS Immunochemistry and immunogenetics Inflammatory bowel disease Intra and intercellular signalling
Medical Law Medical Sciences, Research Membrane and protein trafficking Oncogenes, apoptosis and tumour development
Oral diseases and Oral medicine Oral pathology Pathophysiology Prostate cancer
Quantitative and molecular genetics RET ONCOGENE ACTIVATION RNA processing, stability and degradation Regulatory methods of gene expression
Role of oestrogens in age related urogenital diseases SIGNAL TRANSDUCTION TAQMAN RT-PCR TYROSINE PHOSPHORYLATION
Thyroid Cancer Tumour immunology and immunotherapy Virology and viral pathogenesis
 
Research Projects
Project title Current Projects
Summary Irish Cancer Society Prostate Cancer Research Consortium 2011-2016 Work Package 3: Integrated mRNA and miRNA signatures Sheils O- [coPI] • Merck Serono Validation of k-ras testing in colorectal samples Sheils O [PI] €5000 2011-12 • Amgen Validation of KRAS detection in colorectal samples Sheils O [PI] €5000 2011-12 • BDI 2 CSET (Onc 1 project) SFI Sheils O [co-investigator] Total €19.2M TCD component €991K 2010-1015 • EU 7th FP grant (FP7-HEALTH-2007-A) Sheils O [co-investigator] ‘Automatic Cancer Screening Based on real-time PCR’ “AutoCast” Total €4,188,503.00 TCD component €682K 2010-2013 • EU 7th FP grant (FP7-HEALTH-2007-A) Sheils O [co-investigator] Project number 257073 PASCA—Platform for Advanced Single Cell-Manipulation and Analysis Total €3,000,000 TCD component €700K 2010-2013 • EU 7th FP grant (FP7-HEALTH-2010-Cp-FP) Sheils O [PI] Project Number: 258759-2 Fast Automated Multiplex Analysis of Neonatal Sepsis Markers on a Centrifugal Microfluidic Platform ‘ASCMicroPlat’ Total €2,452,517 TCD component €686K 2011-2015 • The Irish Cancer Society [2008-2012] • Sheils O [co-PI] ‘Hsa-miR-141 and hsa-miR-223 are central to Ovarian Serous Carcinoma Pathogenesis through regulation of JAG1 and SMARCD1 proteins’ Role: Co-Principal Investigator • The Emer Casey Foundation [2008-2012] Sheils O [co-investigator] ‘ The role of hypoxia in chemoresistance in ovarian cancer’ Role: Co-Investigator • The Emer Casey Foundation [2008-2012] Sheils O [co-investigator] ‘Discovering novel signatures of early ovarian cancer’ Role: Co-Investigator • Health Research Board [2004-2012] Sheils O [co-P.I.] ‘PhD training site grant’ Role: Co-Principal Investigator • HRB_HRA/2012/82 Sheils O [co-investigator] 2012 - 2015, Title: "Understanding the role of cancer stem-like cells in resistance to radiation using a clinically-relevant model of radioresistance in oesophageal adenocarcinoma". €291,357.
Funding Agency
Programme
Type of Project
Date from
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Person Months


Project title Molecular Pathology of Thyroid Disease
Summary Current research being undertaken by our group aspires to elucidate the relationship between ret/PTC-1 activation and its associated morphological patterns, by investigating the link between ret/PTC-1 activation and expression of cell adhesion molecules such as E-Cadherin, and the catenin family of proteins. An associated project is underway to characterise ret/PTC3 positive papillary thyroid carcinomas and correlate the findings with disease manifestation. The focus of the proposed study is to broaden the scope of the current research, by using genome wide analysis of diagnostic cohorts of thyroid tumours, to attempt to integrate morphologic and molecular biological findings as suggested by Rosai et al. This would culminate in the establishment of functional genomics of diagnostic cohorts. . It will comprehensively determine levels of expression of gene targets across a spectrum of thyroid disease - from normal, through autoimmune thyroiditis to papillary thyroid carcinoma and its variants (Follicular variant, Tall cell variant, Columnar cell variant, Hurthle cell papillary carcinoma) using comparative genomic hybridisation (CGH) and micro-array technology.
Funding Agency CRI, HRB, Applied Biosystems
Programme
Type of Project
Date from 2000
Date to 2010
Person Months


Project title Head and Neck Oncology
Summary Investigators: Dr. Esther O’Regan (PhD Candidate) Dr. Mary Toner Prof. Conrad Timon Dr. Orla Sheils Prof. John O’Leary Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy that is the sixth most common neoplasm in the world today. This tumour usually afflicts middle to older-aged individuals with a history of tobacco and alcohol use. However recent evidence suggests that there is an increased incidence of HNSCC in individuals in patients under the age of 40, who have not been chronic users of tobacco and alcohol. Genome wide evaluation of tumours is possible. Our group plans to determine the molecular genetic alterations associated with HNSCC in young people, and compare it to those in an older population. Rather than compare the commonly altered chromosomal regions in typical HNSCC, with the same regions in HNSCC affecting a younger population, we plan to perform a genome wide analysis of HNSCC in a cohort of young individuals, in order to identify potential candidate genes that may be significant in the tumorigenesis occurring in this young population. The hypothesis is that HNSCC in young patients (without significant risk factors) is a distinct disease.
Funding Agency CRI
Programme
Type of Project basic research
Date from 2002
Date to 2006
Person Months


Project title Molecular Markers in Cervical Cancer
Summary Recently, our group in the Department of Histopathology has identified a novel set of molecular markers for use in cervical screening programmes. The markers include HPV type, load and integration status, cdc6 and mcm5 expression, telomerase expression and telomeric stabilization/lengthening. Preliminary data suggests that cdc6 and mcm5 (proteins involved in DNA replication) selectively mark dyskaryotic cells in smears and tissue biopsies. The ability to isolate individual dyskaryotic cells from CIN/cGIN and malignant cells from squamous and glandular carcinomas can now be achieved using LCM technology. The above investigators will attempt to identify the mechanism of cdc6 and mcm5 localisation in the nuclei of dyskaryotic cells, and in tandem will examine the influence of HPV infection, telomerase expression and telomeric lengthening/stabilization on such localization phenomena. The experiments will involve geographical isolation and CGH array analysis of cells in CIN 1,2,3,cGIN and invasive squamous and glandular carcinomas of the cervix.
Funding Agency HRB, CRI, Applied Biosystems
Programme
Type of Project
Date from
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Project title Molecular Profiling in Prostate Cancer
Summary The purpose of this project is to study the genetic profile of pre-invasive prostatic neoplasia and subsequent stages of prostatic carcinoma in order to identify genetic discriminators of disease progression. This knowledge could form the basis for the development of new treatment strategies. Prostate cancer is a major world-wide problem, and is the second commonest cancer in men in Ireland. The number of newly diagnosed cases has increased in men of all ages. Prostate cancer has a high mortality rate, and accounts for almost 500 deaths in Ireland annually. The number of deaths is increasing by 3.5% per annum. The rising mortality rate may be due to a number of factors, including undertreatment. One of the major problems and challenges in prostate carcinoma is to predict the outcome of individual patients. Diagnosis of prostatic carcinoma is usually made on prostate biopsy, performed for a raised PSA. In addition, prostatic carcinoma may be diagnosed incidentally in transurethreal prostatic resection (TURP) specimens, performed for benign prostatic disease. Such tumours appear to be biologically more indolent compared with clinically suspected prostate cancers, and this may be due due a different genetic profile. There is no laboratory test currently available which will predict progression of disease. Knowledge of genetic changes underlying initiation, development and progression of prostate carcinoma is limited, and no specific genetic event has yet been identified. We hypothesise that demonstration of chromosomal gains and losses using CGH micro-array technology may identify genetic markers for disease progression.
Funding Agency AMNCH trust, Applied Biosystems
Programme
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Date from
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More Research Projects>>>
 
Publications and Other Research Outputs
Peer Reviewed
Nucera C, Eeckhoute J, Finn S, Carroll JS, Ligon AH, Priolo C, Fadda G, Toner M, Sheils O, Attard M, Pontecorvi A, Nose V, Loda M, Brown M., FOXA1 is a potential oncogene in anaplastic thyroid carcinoma, Clinical Cancer Research, 15, (11), 2009, p3680-3689
Notes: [PMID: 19470727]
TARA - Full Text
More Publications and Other Research Outputs >>>
 

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Last Updated:21-AUG-2014