Supervisor View Full Details

Supervisor View 2
October 3, 2016
Supervisor View Full Details 2nd
October 12, 2016

Prof Orla Sheils

Department:Histopathology

Division:Medicine

Organisation:Trinity College Dublin

Webpage:http://people.tcd.ie/osheils

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Research Fields
  • cancer/oncology
Postgrad Medical Specialites
  • Pathology
Medical Subspecialties
  • Other
Other Medical Specialties:

Molecular Pathology, Molecular Diagnostics

My Work

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 metastasis of solid tumours, and to apply this knowledge to improving disease prevention, detection, diagnosis, and treatment. I have a particular interest in developing novel molecular diagnostics. Translational patient centered research is the common theme throughout my research, linking identification of disease processes with targets for early disease detection or classification.
Ongoing research is examining the pivotal role of co-morbidities in Non Communicable Diseases. We are specifically working to identify synergistic effects of disparate patho-biology, including host immune system and metabolism, lifestyle, and environmental factors linking prognosis with multi-morbidities or indeed resilience to disease.
Other specific areas of research include:
? understanding the interaction between environment/exposome and genes/their expression.
? identifying and isolating biologically relevant Circulating Tumour Cells
? identifying rare mutations among Cell Free DNA samples
? understanding the interplay between platelets and coagulation system with regard to enablement of metastasis
? Identifying mechanisms of immune evasion in metastasis

Potential Projects

Project 1: Liquid Biospy ? a non invasive tumor tracker in Lethal Cancers

Despite best efforts, true early detection of cancer and its upstaging to metastatic disease remain unmet clinical challenges. Blood-based biomarkers (liquid biopsy) in cancer have considerable potential for the initial detection, diagnosis and monitoring of cancer.
Circulating tumour cells (CTC) and Cell Free Tumour DNA (cfDNA) represent promising, new, real time biological tracking devices of disease progression with scope for impact in diagnosis, monitoring and screening for optimal therapy.
This project will focus on lethality signatures within liquid biopsies in obesity/metabolic syndrome, inflammation and hypercoagulation driven cancers. These elements are synergistically linked with engagement of one, upstaging activation of the others. The roles of immune evasion and tumor induced inflammation will be correlated with CTC phenotypes ex-vivo and using animal models.

Project 2: Molecular re-classification of thyroid tumours ? assessment of risk: benefits and development of a molecular monitoring tool

Recently, an international panel of pathologists and clinicians has reclassified a type of thyroid cancer to reflect that it is noninvasive and has a low risk for recurrence.
The panel renamed encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The change in nomenclature will affect the clinical care and management of a significant proportion of patients (predominately young, female) and monitoring systems need to be implemented to accurately detect any upstaging of disease behavior.
This project will involve a temporal assessment of mutational status among Irish Patients with thyroid cancer (including BRAF/ret/PTC and RAS) to identify the subset of dedifferentiating lesions.
A NGS strategy will be employed to generate a molecular taxonomy using primary and metastatic tissue, FNA and liquid biopsy (CTC and cfDNA) samples. The objective will be to establish and clinically validate a screening and monitoring algorithm for patients to be implemented into a ?watchful waiting/active surveillance? management approach.
A second arm of this project will involve a psycho-social investigation of the effects on young female patients of being entered into a potentially long term watchful waiting programme on general well-being.