Contact: Northern Ireland Centre for Stratified Medicine

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Visiting Professors

  • Professor Lady Maeve Rea
  • Professor Maurice O’Kane

PhD Researchers

Amanda Eakin

Thesis title : Discovery of biomarkers of DMARD response in early stage rheumatoid arthritis

Supervisor: Prof Tony Bjourson, Dr David Gibson

The project focuses on identifying genetic alterations on the Glucagon-like peptide-1 receptor (GLP-1R) with the aim of identifying sequences of nucleotides indicative of either a responder or non-responder to GLP-1 analogue treatment or an individual that may experience adverse events such as nausea or vomiting. These will be further assessed by validating associated protein and genetic markers linked to weightless and improved glycaemic control.

Andrew English

Thesis title : Biomarkers for stratification of responders and non responders to GLP-1 analogues in Type 2 diabetes

Supervisors : Dr Paula McClean, Dr Catriona Kelly

The project focuses on identifying genetic alterations on the Glucagon-like peptide-1 receptor (GLP-1R) with the aim of identifying sequences of nucleotides indicative of either a responder or non-responder to GLP-1 analogue treatment or an individual that may experience adverse events such as nausea or vomiting. These will be further assessed by validating associated protein and genetic markers linked to weightless and improved glycaemic control.

Tahanver AhmedTahanver Ahmed

Thesis title : Stratification of rheumatoid arthritis patients by immunogenicity to biologic drugs

Supervisors : Professor Tony Bjourson, Dr David Gibson

Biological drugs targeting tumour necrosis factor (TNF) are an invaluable treatment option for patients who are ineligible or unresponsive to traditional anti-rheumatic drugs. These drugs show an initial response in 70% of patients. However, 50% of responders become insensitive to biological therapy overtime perhaps due to development of anti-drug antibodies.
In this project we aim to identify genotypic and pharmacokinetic biomarkers which will be used to develop a model through which patients who initially respond, but then become non-responsive may be forecast; thereby allowing selection of the most appropriate treatment option and thus improving patient care and generating healthcare savings.

Coral Lapsley

Thesis title : Stratified Medicine in Health: Can immune status be used to predict response to antidepressant treatment?

Supervisors : Dr Elaine Murray, Prof Tony Bjourson

The development of a biomarker panel to predict antidepressant treatment response in patients with depression. Coral is investigating the potential of biological markers at protein, epigenetic and genetic level, and the overall aim is to be able to stratify patients with depression into responders and non-responders to first line antidepressant strategies.
Successful biomarkers, integrated with clinical information, could greatly reduce the time for patients with depression to receive effective treatment.

Jessica Niggel

Project Title: Evaluating the effectiveness of DNA methylation patterns for patient stratification in major depressive disorder.

Supervisors: Dr. Elaine Murray, Prof. Tony Bjourson, Prof. Colum Walsh

Depression is the most commonly diagnosed mental health disorder worldwide and is characterised by low mood, anhedonia, and in severe cases suicidal behaviour. Northern Ireland has one of the highest rates of depression in Europe and the highest incidence of suicide in the UK. Despite it’s prevalence, the pathophysiology of depression and risk factors for suicide are poorly understood.

Although antidepressants can be very effective in treating depression there is a high rate of inter-individual variability in their efficacy. Only about 30% of patients achieve full remission following antidepressant treatment. An additional 30% of individuals are described as treatment resistant following failure to respond to two successive antidepressants. Treatment resistant depression is associated with increased symptom severity, increased rate of relapse and lower long-term quality of life.

There is a clinical need to develop biomarkers to assist in diagnosis of depression and identify individuals at risk of treatment resistance. Genetic and environmental factors are linked to increased risk for depression and their interaction may lead to development of mental illness. Preliminary studies have identified DNA methylation patterns that are associated with severe depression, treatment resistance and suicidal behaviour. Depressive disorders and response to antidepressants have also been linked to inflammatory status. The aim of this study is to identify epigenetic and inflammatory markers that can be used to assist in diagnosis and treatment selection for individuals with depression.

Boon Chin Tan

Project title: An in vitro investigation of endo-cannabinoid receptor modulation of inflammation and pain pathways in arthritis

Supervisors: Dr. David Gibson, Dr. Elaine Murray and Dr.Steven Watterson.

Rheumatoid arthritis (RA) is an autoimmune disorder with multifactorial causes of chronic inflammation and pain. Current treatments for RA target inflammation and pain within joints to limit joint destruction and disability. However these medications are poorly tolerated, carry inherent risk of adverse events and frequently do not result in meaningful pain relief. In the last twenty years, research has revealed that endocannabinoid receptors can modify the inflammatory and neurotransmission activity of cells within the immune and nervous system. Phytocannabinoid compounds are thought to have anti-inflammatory, analgesic and anti-tumour effects. This project aims to investigate the mechanism of a non-psychoactive phytocannabinoid upon in vitro inflammatory and pain signalling pathways. An in silico pathway map of the endocannabinoid system effects upon the wider pathology of RA will be created and validated with in vitro data. These studies will contribute to pre-clinical knowledge of efficacy required for in human trials.

Owen Connolly

Thesis title: Identification and regulation of toxic elements secreted by ALS vesicles.

Supervisors: Dr Stephanie Duguez & Dr William Duddy

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurodegenerative disease characterised by degeneration of upper and lower motor neurons manifesting in severe muscular atrophy and respiratory failure. Work in the lab suggests that extracellular vesicles (EV) from ALS patients exert toxicity when added to healthy cells and so this project aims to: (1) regulate exosome secretion using siRNA and chemicals known to impair secretory pathways, thereby reducing the toxicity of the ALS secretome (2) regulate the production and secretion of specific EV elements that are thought to promote toxicity. This project aims to identify potential biomarkers and therapeutic targets for the diagnosis and treatment of ALS.

Joseph Mc Laughlin

Thesis title: Metagenomic and culture-based characterisation of Propionibacterium acnes communities in patients with severe recalcitrant papulopustular and nodular acne.

Supervisors : Dr Andrew McDowell, Prof Tony Bjourson

The widespread use of topical and oral antibiotics for the treatment of acne has now led to the development of P. acnes strains that are resistant to first line antibiotic therapies. The emergence of such ‘super-bug’ strains is extremely alarming, raising the possibility that in the future patients will not respond to conventional antibiotics currently used to manage the condition. Indeed, patients with severe and recalcitrant forms of the condition due to multi-drug resistant strains are already being referred to secondary and tertiary care settings for specialised treatment. Even more worrisome is that some of these patients are also non-responsive to oral retinoids.
Despite these serious problems, our knowledge of the aetiology of these most devastating forms of resistant acne is poor. This British Skin Foundation funded project will therefore attempt to better understand the underlying microbiology and pathophysiology of this type of acne, and develop novel antimicrobial treatments as alternates to antibiotics. This work should provide an invaluable platform for the generation of diagnostics that stratifies patients for the risk of aggressive forms of acne, and identify treatment non-responders

Laura Le Gall

Thesis title : ALS signature in muscle stem cells : intercellular communication altered between muscle and nerve

Supervisors : Dr Stephanie Duguez

In line with other studies, S Duguez’s team have obtained data supporting that muscle involvement in ALS pathogenesis may not only be considered as a consequence of denervation but participates to the non-cell autonomous degenerative process. We have identified both a robust ALS gene expression signature and a new driver of toxicity in muscle cells and in muscle cell to motor neuron interactions in ALS patients.
Laura Le Gall joined the team in 2015 to pursue her joint PhD between Université Pierre & Marie Curie P6 Thesis title : Sorbonne Universitées and Ulster University. She will explore this novel muscle component to ALS pathology. The purpose of her PhD is to (1) characterize the composition of secreted muscle vesicles (mRNA, microRNA, protein and metabolite content); (2) in collaboration with Cedric Raoul’s (INSERM, Montpellier, France) and Cecile Martinat’s (I-Stem, Evry, France) teams determine the effect of muscle vesicles on neurons; and (3) identify the toxic transcripts and proteins secreted through the vesicles.

Melody El Chemaly

Thesis title : Biomarkers in cardiovascular disease

Supervisors : Dr Victoria McGilligan, Dr Aaron Peace

Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Cardiac biomarkers need to be developed in order to predict and prevent the occurrence of major adverse cardiovascular events. We are in the process of investigating potential inflammatory markers involved in endothelial dysfunction and platelet activation. The ultimate goal is to use those markers to better stratify patients at high risk of developing a cardiovascular event and give them the recommended treatment as early as possible.

Michael Jones

Thesis title : Developing an Integrated Approach to Identifying and Validating Candidate Therapeutic Compounds for Triple Negative Breast Cancer

Supervisors : Professor Tony Bjourson and Dr Shu-Dong Zhang

The project aims to develop an integrated approach to the identification and subsequent validation of candidate drugs with potential anti-cancer properties. Triple negative breast cancer will be the primary disease to test out this novel approach. Once developed, the process can be similarly applied to other diseases.

Vanessa Milla

Thesis title : Characterization of the metabolite content of ALS exosomes: identification of ALS biomarkers and determination of their role in physiopathology

Supervisor : Dr Stephanie Duguez

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, characterised by a severe muscle atrophy and motor neurone degeneration leading to death within 5 years after the onset. ALS is notoriously difficult to diagnose and requires exclusion of mimicking diseases. S.Duguez’s team has shown that ALS muscle cells secrete toxic vesicles that may play a role in the spreading of physiopathology. The purpose of this PhD is to (1) characterize the metabolite profiles of ALS vesicles and identify specific biomarkers, and (2) determine the role of secreted vesicles in the metabolism switch observed in ALS patients.

Rebecca Kennedy

Thesis title : Stratification in Alzheimers Disease

Supervisors : Dr Paula McClean

The project will focus on stratification of Alzheimer’s disease patients with respect to age of onset, rate of progression, presence of challenging behaviours and sleep disturbance and response to currently available therapeutics.

Ryan Kelsey

Thesis title : The Effect of CFTR on islet development and signalling

Supervisors : Prof Neville McClenaghan, Dr Catriona Kelly

Cystic Fibrosis Related Diabetes is the largest co-morbidity associated with CF but the exact mechanism for CFRD development remains unclear. The aim of this project is to explore the potential role of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) on islet formation, function and in intracellular communication. This project is part of a CF Trust funded Strategic Research Centre comprising researchers from Ulster, Newcastle, Lund, Iowa and Hungary.

Stephen Morgan

Thesis title : Network Medicine to explore the role of mucle in ALS

Supervisors : Dr William Duddy and Dr Stephanie Duguez

Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neuron disease (MND) with life expectancy at diagnosis of around 2-5 years. The team has previously identified muscle secreted microvesicles to play a potential role in ALS pathology. This project aims to employ systems biology and network medicine approaches to understand the role of muscle in ALS and other MND’s. We will use in-house and public datasets, from muscle cells and tissue, to construct networks of functional associations representing known interactions between genes, proteins and other biomolecules in ALS and other MND’s. We will identify groups of interacting genes or proteins called disease modules that are dysregulated by the pathology. The aim of identifying these disease modules is to understand the pathological role of muscle in ALS, and what molecular changes are specific to ALS.

Angelina Thomas Villikudathil

Thesis Title: Machine Learning based computational method development for biomarker discovery in inflammatory diseases

Supervisors: Dr Priyank Shukla and Professor Tony Bjourson

The concern for better diagnostics and tailored therapies for patients with multi-morbid inflammatory disease conditions raises a major need for their stratification. By determining the molecular phenotype and developing a range of biomarkers to assess individual patients is highly crucial. The combination of multi-omics data and clinical health records from multi-morbid patients could aid in developing improved machine learning based predictive tools that can effectively stratify multi-morbid patients and more accurately predict treatment outcomes. This project focuses on identifying biomarkers using machine learning based algorithms that can stratify patients with respect to: a) inflammation and comorbidity or multi-morbidity and b) inflammatory disease sub-groups which respond to specific treatments.

Past PhD Researchers

Fiona Manderson Koivula

Thesis title : The Role of the Endocrine Pancreas in the Development of CF-related Diabetes

Supervisors : Dr Catriona Kelly, Prof Neville McClenaghan

This project focuses on Cystic Fibrosis-related Diabetes, and specifically the structural and functional effects of the mutant CF-causing gene (CFTR) on the endocrine pancreas. Using stable cell lines and primary tissue, we aim to elucidate the mechanisms behind impaired glucose homeostasis and insulin secretion in CF, which we hope will identify better treatment leading to a better quality of life for CF patients.

Philip EganPhilip Egan

Thesis title : Towards Individualisation of Combination Chemotherapy in Myeloma

Supervisors : Dr Caroline Conway, Prof Tony Bjourson

Multiple myeloma is an incurable cancer although several drug treatments are available that can significantly prolong life. Relapse is inevitable when the tumour develops drug resistance after a variable length of time. Genetic and cytokine markers may allow more accurate prediction of the time taken to relapse, allowing treatment to be better tailored to the individual

Declan McGuigan

Thesis title : Predicting Response to Treatment in Type 2 Diabetes

Supervisors : Dr Catriona Kelly, Dr Paula McClean

Type 2 diabetes is a chronic disease for which there are numerous treatments available. However, it is common to see a variation in how individuals respond to these. The focus of this project is the response to, and adverse events associated with, sulphonylurea treatment. Sulphonylureas are a common first line treatment option, and their use has been associated with an increased risk of cardiac disease.

Eliza Yankova

Thesis title : Towards a Personalised Medicine Strategy to Reduce Prostate Cancer Risk in Men

Supervisors : Dr Andrew McDowell, Dr David Gibson

Understanding the role of the anaerobic bacterium Propionibacterium acnes in the aetiology of prostate cancer, with an emphasis on the identification of novel biomarkers of infection.

Andrew Parton

Thesis title : The dynamics of cholesterol metabolism and atherosclerosis across population subgroups

Supervisor(s) : Dr Steven Watterson, Dr Victoria McGilligan

The project involves the creation of a mathematical model of atherosclerosis, then using online data sources, bioinformatics tools and statistical analysis techniques to study how the dynamics of this pathway model change based upon publicly available genomic data.