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Professor Orla Sheils

Vice Provost - Chief Academic Officer (Office of Chief Academic Officer)
Professor in Molecular Diagnostics (Histopathology)
 (3531896) 3284
      
Profile Photo

Professor Orla Sheils

Vice Provost - Chief Academic Officer (Office of Chief Academic Officer)

 osheils@tcd.ie

 

Professor in Molecular Diagnostics (Histopathology)

 (3531896) 3284


Vice-Provost/Chief Academic Officer. Professor Sheils has a ScD and PhD in Molecular Pathology from Trinity College Dublin and a MA in Medical Law and Ethics from Kings College London. She is Professor of Molecular Diagnostics, and the underlying theme of her 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. She has a particular interest in developing novel molecular diagnostics. Translational research is the common theme throughout Prof Sheils' research, linking identification of disease processes with targets for early disease detection or classification. She works closely with industry bringing novel technologies and applications to the translational research setting. She is a leader in multidisciplinary molecular pathology, who has championed a niche area facilitating interaction between basic science, translational research, clinical service provision and biotechnology. In this regard she has built an independent, globally recognised research group focused on molecular diagnostics and identification of molecular features of disease progression. Through her research, she has uncovered pivotal mutations descriptive of several solid tumours including thyroid, cervix, ovary, colon, head & neck and lung. These discoveries form peer- reviewed publications, populate pathology textbooks and are the basis for the translation of assays that she designed to transform clinical diagnostics. In research, her commitment to translational medicine is underpinned by the singular objective of using clinical research to advance human health. The underlying theme of her 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. She has a strong track record in developing novel molecular diagnostics and translating this research into clinical service. As a teacher, Prof Sheils has embraced curricular reform and has introduced a variety of innovations into undergraduate and postgraduate teaching. Her commitment to students was recognized when she was invited to become President of the 134th session of the Biological Society of Dublin University in 2008. Her qualifications in science, medicine, law and ethics enable her to work and communicate effectively across and between a wide range of disciplines and in 2012 she was awarded as Provost's Teaching Award in recognition of her pioneering approach to teaching medical science and ethics. In 2012, Prof Sheils was appointed Chair of College's Research Ethics Policy Committee (REPC) having chaired the Faculty of Health Sciences Research Ethics Committee (REC) for the previous 7 years. In this role, she developed policy documents on the criteria for RECs within College, Good Research Practice, Procedures for Ethical Review, External Access and she was responsible for aligning Research Ethics Committees across College. In 2016 Professor Sheils was appointed as founding Director of the Trinity Translational Medicine Institute where she leads an exclusively health sciences- focused educational and research institution, embedded within the acute hospital setting. TTMI's strategy of improving human health through translational research is predicated on clinical, laboratory-based and health service research informed by real world clinical bedside problems, and societal and global health challenges. She became Dean of the Faculty of Health Sciences in 2019 and was appointed Vice-Provost/Chief Academic Officer in 2021
  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   Regulatory methods of gene expression   RET ONCOGENE ACTIVATION   RNA processing, stability and degradation   Role of oestrogens in age related urogenital diseases   SIGNAL TRANSDUCTION   TAQMAN RT-PCR   Thyroid Cancer   Tumour immunology and immunotherapy   TYROSINE PHOSPHORYLATION   Virology and viral pathogenesis
Project Title
 Current Projects
From
To
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.
Project Title
 Molecular Pathology of Thyroid Disease
From
2000
To
2010
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
Project Title
 Head and Neck Oncology
From
2002
To
2006
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
Project Type
basic research
Project Title
 Molecular Markers in Cervical Cancer
From
To
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
Project Title
 Molecular Profiling in Prostate Cancer
From
To
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

Page 1 of 2
Details Date
Member of the Advisory Committee - Societal Challenge 1, Health & Demographic Change. European Commission 2013
Board Member - European Institute of Women's Health 2017
Associate Editor Irish Journal of Medical Science 2017
National workgroup on Bio-banking 2012
Member, MMI Cancer Principal Investigators, Trans-institutional grouping of Principal Investigators leading research on Cancer themes 2010
Associate Editor BMC Cancer 2010
Member, Core Technology PI's, DMMC Principal Investigators leading the development of core technology platforms. 2006
Wellcome Trust - Reviewer 2005
Reviewer for South African Medical Research Council 2004
Scientific Advisor - I act in an advisory capacity for ThermoFisher, offering insight into planning and development of molecular diagnostic tools, ensuring the internationally renowned profiles of the Discipline of Histopathology and of College are maintained and positioning us to have early access to novel products and have input into their construction. 2010
Reviewer for Hong Kong Earmarked Research Grants (ERG) [administered by the Research Grants Council (RGC) ] 2005
Member of Editorial Board of Journal of Endocrine Pathology 2009
Advisor to the National Council with expertise in Medical Teaching -USI Academic Affairs Advisory Panel. 2015
Reviewer for journals including: Oncogene, Nature Biotechnology, Nature Medicine, Journal of Clinical Endocrinology and Metabolism, Molecular Cancer, Molecular Endocrinology, Journal of Pathology, Modern Pathology, International Journal of Surgical Pathology, DU Law Review 2003
Language Skill Reading Skill Writing Skill Speaking
English Fluent Fluent Fluent
Details Date From Date To
Member of the Pathological Society of Great Britain and Ireland 2001 present
Member of Medico-legal Society of Ireland 2006 present
Fellow of the Royal College of Pathologists 2007 present
Fellow of the Institute of Biomedical Sciences 2016 present
Murchan, P. and Ã" Broin, P. and Baird, A.-M. and Sheils, O. and P Finn, S., Deep feature batch correction using ComBat for machine learning applications in computational pathology, Journal of Pathology Informatics, 15, (100396), 2024, Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Murchan, P. and Baird, A.-M. and Ã" Broin, P. and Sheils, O. and Finn, S.P., Surrogate Biomarker Prediction from Whole-Slide Images for Evaluating Overall Survival in Lung Adenocarcinoma, Diagnostics, 14, (5), 2024, Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Darker CD, Mullin M, Doyle L, Tanner M, McGrath D, Doherty L, Dreyer-Gibney K, Barrett EM, Flynn D, Murphy P, Ivers JH, Burke E, Ryan M, McCarron M, Murphy P, Sheils O, Hevey D, Leen A, Keogh L, Walls B, Bennett AE, Petersen F, Nolan A, Barry JM., Developing a health promoting university in Trinity College Dublin-overview and outline process evaluation, Health Promotion International, 38, (4), 2023, p1 - 14, p1-14 , Journal Article, PUBLISHED  DOI
Devenney, K. and Murphy, N. and Ryan, R. and Grant, C. and Kennedy, M.J. and Manecksha, R.P. and Sheils, O. and McNeely, M.L. and Hussey, J. and Sheill, G., Implementing a physiotherapy led cancer exercise programme in a National Cancer Centre: the FIXCAS study, Physiotherapy (United Kingdom), 120, 2023, p27-35 , Notes: [cited By 1], Journal Article, PUBLISHED  DOI
O†Shaughnessy, M. and Sheils, O. and Baird, A.-M., The Lung Microbiome in COPD and Lung Cancer: Exploring the Potential of Metal-Based Drugs, International Journal of Molecular Sciences, 24, (15), 2023, Notes: [cited By 9], Journal Article, PUBLISHED  DOI
Sheill G, L Brady, B Hayes, AM Baird, E Guinan, R Vishwakarma, C Brophy, T Vlajnic, O Casey, V Murphy, J Greene, E Allott, J Hussey, F Cahill, M Van Hemelrijck, N Peat, L Mucci, M Cunningham, L Grogan, T Lynch, RP Manecksha, J McCaffrey, D O'Donnell, O Sheils, J O'Leary, S Rudman, R McDermott, S Finn, ExPeCT: a randomised trial examining the impact of exercise on quality of life in men with metastatic prostate cancer, Supportive Care in Cancer, 31, 2023, p292-, Journal Article, PUBLISHED  DOI  URL
Ryan, K.M. and Smyth, P. and Blackshields, G. and Kranaster, L. and Sartorius, A. and Sheils, O. and McLoughlin, D.M., Electroconvulsive Stimulation in Rats Induces Alterations in the Hippocampal miRNome: Translational Implications for Depression, Molecular Neurobiology, 60, (3), 2023, p1150-1163 , Notes: [cited By 2], Journal Article, PUBLISHED  DOI
Kate Dinneen, Anne-Marie Baird, Ciara Ryan, Orla Sheils, The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma, Frontiers in Molecular Biosciences, 2021, Notes: [https://doi.org/10.3389/fmolb.2021.600373 10.3389/fmolb.2021.600373 ], Journal Article, PUBLISHED
John Greene, Anne-Marie Baird, Marvin Lim, Joshua Flynn, Ciara McNevin, Lauren Brady, Orla Sheils, Steven G Gray, Raymond McDermott, Stephen P Finn, Differential CircRNA Expression Signatures May Serve as Potential Novel Biomarkers in Prostate Cancer, Frontiers in cell and developmental biology, 9, 2021, p334-, Notes: [https://doi.org/10.3389/fcell.2021.605686], Journal Article, PUBLISHED
McNevin CS, Cadoo K, Baird AM, Murchan P, Sheils O, McDermott R, Finn S., Pathogenic BRCA Variants as Biomarkers for Risk in Prostate Cancer., Cancers, 13, (22), 2021, Journal Article, PUBLISHED  DOI
  

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Jose L Costa, Robbert Weren, Anna Maria Rachiglio, Andrea Mafficini, Henriette Kurth, Anne Reiman, Audrey Didelot, Alexander Boag, Claudia Vollbrecht, Kazuto Nishino, Harriet E Feilotter, Pierre Laurent-Puig, Orla Sheils, Aldo Scarpa, Marjolijn Ligtenberg, Ian A Cree, Michael Hummel, Jose Carlos Machado, Nicola Normanno, Multi institutional evaluation of a new NGS assay for mutation detection from cfDNA in lung cancer, Cancer Research, 13, American Association for Cancer Research, 2017, pp5694 - 5694, Conference Paper, PUBLISHED
M O'Donovan, I Silva, OM Sheils, JJ O'Leary, Molecular Analysis of Primary Effusion Lymphoma, 91st annual meeting USCAP, Chicago, IL, 2002, Conference Paper, PUBLISHED
M O'Donovan, I Silva, C. Martin, SB Lucas, OM Sheils, JJ O'Leary, Expression Profiling of Kaposi's Sarcoma reveals dysregulation of immunomodulatory, pro-inflammatory, connective tissue and vascular/haematological related genes, Annual Meeting of the Pathological Society of Great Britain and Ireland, Dublin, 2002, Conference Paper, PUBLISHED
P Smyth, S Finn, JJ O'Leary, O Sheils, E-cadherin expression is reduced in ret/PTC-1 but not ret/PTC-3 activated thyroid neoplasms, neoplasms., Dublin, 2002, Conference Paper, PUBLISHED
M O'Donovan, I Silva, C Martin, O Sheils, JJ O'Leary, Molecular Analysis of Primary Effusion Lymphoma using mFISH and CGH analysis demonstrates common molecular genetic pathways, Annual Meeting of the Pathological Society of Great Britain and Ireland, Dublin, 2002, Conference Paper, PUBLISHED
N Murphy, M Ring, A Killalea, F Mulcahy, E McGuinness, M Griffin, C Martin, O Sheils, JJ O'Leary, p16ink4a, cdc 6, mcm 5 and HPV status: predictive biomarkers of cervical pre-neoplasia?, Annual Meeting of the Pathological Society of Great Britain and Ireland, Dublin, 2002, Conference Paper, PUBLISHED
C Hughes, C Martin, O Sheils, B Loftus, JJ O'Leary, Development of a detailed molecular profile for prostate cancer, Annual Meeting of the Pathological Society of Great Britain and Ireland, Dublin, 2002, Conference Paper, PUBLISHED
A Crowley, JJ O'Leary, O Sheils, C Martin, F Taulo, J Anthony, C O'Herlihy, BM Byrne, Quantification of fetal DNA in the peripheral blood of women with pre-eclampsia in South Africa and Ireland -a useful marker of disease severity, Annual Meeting of the Pathological Society of Great Britain and Ireland, Dublin, 2002, Conference Paper, PUBLISHED
I Silva, M O'Donovan, N Murphy, O Sheils, SB Lucas, JJ O'Leary, Genome wide evaluation of a HHV8 virally transformed co-hybrid cell culture model system, Annual Meeting of the Pathological Society of Great Britain and Ireland, Dublin, 2002, Conference Paper, PUBLISHED
CM Martin, V Uhlmann, O Sheils, L Pilkington, I Silva, A Killalea, J Walker Smith, SB Murch, M Thompson, A Wakefield, JJ O'Leary, Potential viral pathogenic mechanism for new variant inflammatory bowel disease, Annual Meeting of the Pathological Society of Great Britain and Ireland, Dublin, 2002, Notes: [ ], Conference Paper, PUBLISHED

  


Page 1 of 3
Award Date
FTCD 2009
Provost's Teaching Award 2012
MA jure oficii 2007
My research is of international consequence and of consequence to individual patients. I have developed a significant programme concerned with molecular diagnostics and prognostics. I have made seminal discoveries in the areas of thyroid and cervical pathobiology. I have procured grants worth >€35M, I have published >120 peer reviewed journal articles and presented my work on the international stage. I am a leader in multidisciplinary molecular pathology. I have championed a niche area facilitating interaction between basic science, translational research, clinical service provision and biotechnology. The significance and transformational value of my work resides in my international recognition, industry disruptive research and benefit to cancer patients quality of life. I am Director of and a Principal Investigator in the Trinity Translational Medicine Institute and a PI in Biomedical Diagnostics Institute at DCU. I work closely with several biotech companies and have procured European Reference Lab status from ThermoFisher. This industry recognition of my research ensures we have pre-commercial launch access to novel chemistries and we act as a beta test site for new technology platforms and analysis kits. My research focuses on elucidating the underlying mechanisms of human disease with a focus on cancer and metastasis of solid tumors. This work is translated into novel assays for better diagnosis and prognostication of patients' disease. I have made seminal discoveries into the pathobiology of cancers including thyroid and cervix, which have resulted in major changes to the way patients are treated. I am a founder member of several international consortia working to establish novel sequencing technologies as routine diagnostic testing regimens in clinical laboratories. My research has been published in international journals at the highest levels and has been incorporated into fundamental pathology textbooks. My research continues to enhance TCD's reputation as an international force in cancer research. The international significance of my research is recognized by invitations to deliver plenary and keynote addresses at leading conferences in Pathology and Human Genetics. Additional transformational significance has seen Trinity College affiliated St James's Hospital become Ireland's first accredited Cancer Diagnostics Laboratory. My position within the Department of Histopathology means that I have an understanding of the diagnostic and prognostic deficiencies within current clinical practice and many of the research innovations made under my supervision have been geared towards enhanced service delivery. Thus there is a spectrum of research in which I am involved from basic science to more translational research with direct application in the clinical setting. My work in early cancer diagnostics and theranostics is recognised globally and has made tangible differences in the way patients are managed. The translation of basic research to clinically relevant assays has had an industry disruptive and transformative influence on molecular diagnostics. I have positioned myself for leadership by building an infrastructure within and outwith of TCD that is unique to the College ecosystem and from which TCD continues to make a real difference in people's lives who are affected by cancer. My translational research positions us to lead cancer related diagnostics in Ireland and beyond. This research will form the bedrock of service provision and interdisciplinary innovation that are central to the aspirations of the newly proposed Cancer Institute at the SJH site. In Summary, my research has led to discoveries highlighting pivotal mutations in cancers and directly influencing improved treatment of patients. In essence my research has been the difference between life or death for many patients.