Our Research

From Bench to Bedside: Translational Research at UCD CRC

The UCD Clinical Research Centre supports research across a wide range of disease areas. In this section we profile a selection of research investigations by clinical speciality.

Should you have any enquiries relating to ongoing projects or if you are interested in learning more, please don't hesitate to contact us. 

Research Area | Infectious Diseases

Dublin City HIV Cohort

Principal Investigator: Prof William Powderley

This is a multicentre study in collaboration with St James and Beaumont Hospitals which aims to provide valuable information on the natural history of HIV and on the emergence of new problems in treated and untreated populations. The data from this cohort may provide insights into issues such as viral evolution and development of resistance in differing populations, development of adverse events in different patient populations of different ethnic and genetic backgrounds and pharmacogenetics of adverse events with an increased understanding of genetic control of drug metabolism.

Bone Toxicities in HIV

In vitro study of effect of HIV and its treatment on bone biology

Principal Investigator : Dr. Peter Doran & Dr. Eoin Cotter

This research focuses on the effects of HIV-1 and its treatment on osteoblast and mesenchymal stem cell lines. Numerous other studies have reported an increased risk of reduced bone mineral density (BMD) in AIDs patients and in particular with certain anti-retroviral treatment regimes such as HIV protease inhibitors (PI). Our research has demonstrated that both HIV viral proteins and PI can affect the function of cultured osteoblasts by modifying inter- and intracellular signalling. We have also shown that HIV viral proteins can alter the development of mesenchymal stem cells into functioning osteoblasts.

Current and ongoing research involves using an ex-vivo model of HIV-1/MSC exposure to further the delineate the effects of HIV-1 on bone and fat biology.

ALTAIR Study

A randomised open label study comparing the safety and efficacy of three different combination antiretroviral regimens as initial therapy for HIV infection (ALTAIR)

Principal Investigator: Dr Paddy Mallon

The primary objective of this study is to compare the virological efficacy of three strategic regimens of initial ART containing a fixed dose formulation of Tenofovir and Emtricitabine with either Efavirenz, Atazanavir boosted with Ritonavir or Zidovudine plus Abacavir in treatment naïve subjects. Currently 261 of the required 300 subjects have been randomised from 15 different countries world-wide.

Therapeutic Drug monitoring

Use in HIV infected pregnant women

Principle Investigator: Dr. Jack Lambert

The use of HIV protease inhibitors (PI) in infected pregnant women is increasing, with the dual purpose of maintaining maternal health and preventing mother to child HIV transmission. Adequate plasma concentrations of antiretroviral drugs are key to achieving and maintaining long-term suppression of HIV replication. Having robust data on drug levels in a large cohort of women in pregnancy will potentially assist in the evaluation and analysis of many maternal and fetal factors which may be important to better understand, benefiting current and future generations of women who receive these drugs in pregnancy. This study to recruit women who are receiving PI’s as part of their HARRT treatment or prophylaxis regimen during prenancy is being carried out in conjunction with The Rotunda Hospital, Dublin and Galway.

Research Area | Respiratory Medicine

The UCD CRC supports significant funded research programmes in the respiratory medicine area,  through its links to the National Lung transplant programme and the national pulmonary hypertension unit at the Mater Misericordiae University Hospital and the National Pulmonary Fibrosis Centre at St. Vincent's University Hospital.

Sarcoidosis Research Programme

Principal Investigator: Dr. Seamas Donnelly

The National Pulmonary Fibrosis Centre at St Vincent's University Hospital is Ireland's leading Centre for the care and management of patients with advanced pulmonary fibrosis. In Ireland the commonest cause of pulmonary fibrosis in young adults is sarcoidosis. While only a minority of these patients develop progressive pulmonary fibrosis, we are unable currently to pinpoint at diagnosis which patients will have self limiting mild disease compared to progressive advanced disease.

Dr Seamas Donnelly and his research group are focused on identifying a genetic imprint within individuals which would allow the identification of patients at high risk of developing more severe disease. Data collected have identified two specific genes which are implicated in sarcoidosis and they are now working on potential mechanisms to reverse this genetic defect which then holds out the promise of focused therapies directed at those patients expressing this genetic signature with the aim of preventing the development of chronic disease.

Interstitial Lung Disease

Principal Investigator: Prof. Michael Keane

The opportunity to promote our understanding of human diseases has never been greater. Buoyed by recent advances in digital technology, analytical biochemistry and sample acquisition together with the sequencing of the human genome, differences between biological specimens that are normal or diseased can potentially be elucidated using new advanced technologies such as microarray analysis and proteomics.

No systematic assessment has been made of the molecular mechanisms and heritability of lung disease in the general patient population or the risk to relatives of affected individuals.. It is now technologically feasible to apply the recent advances in the human genome to the identification of fibrosis susceptibility genes in humans. Preliminary studies using informatics tools designed to evaluate the information content of expression data for each gene on the array suggest that this technology could identify unexpected molecular participants in IPF, and it may allow molecular fingerprinting that could improve the ability to identify sub-classifications of pulmonary fibrosis that might be more informative than the current classification. 

One could use these genetic findings to develop new strategies for screening and diagnosis, to identify novel therapeutic targets for this progressive life-threatening disorder, and to understand further the pathogenesis of advanced lung disease.

 

Research Area | Rheumatology

Assessment of Platelet Function in Patients with Inflammatory Arthritis. Does Control of Inflammation Alter Thrombotic Risk?

Principal Investigator: Prof Geraldine McCarthy.

Rationale: Compared to the general population, there is an increased incidence of cardiovascular events, including myocardial infarction and cardiac death in patients with inflammatory arthritis, including rheumatoid arthritis (RA). This increased risk is mediated by the presence of both traditional risk factors and factors unique to those with systemic inflammatory disorders.

It is postulated that, in patients with RA, chronic inflammation may enhance the development of coronary artery disease and cardiac events, perhaps via the effects of cytokines and/or immune complexes and/or coagulation abnormalities.

Markers of increased systemic inflammation are associated with an increased risk of coronary artery disease. Because of these observations it has been suggested that tight control of inflammation in RA patients could lead to a reduction in the risk of cardiovascular disease. Although the hypothesis has not been adequately tested in a prospective trial, observational data suggest that strict control of inflammation in RA by use of therapy that effectively decreases synovial inflammation may reduce the development and progression of CVD.

Our hypothesis is that part of the benefit in terms of reduction in risk of cardiac events is conferred by a reduction in the thrombogenic potential of platelets by controlling inflammation. This is supported by work which shows that CRP, a major maker of inflammation can increase platelet adhesion to endothelial cells.

We hypothesise that part of this benefit is due to a down regulation of platelet aggregation from a reduction in inflammation and we propose to undertake this study to confirm this.

An Examination of Synovial Fluid in Patients with Osteoarthritis.

Principal Investigator: Prof Geraldine McCarthy

 

Rationale: The disease of osteoarthritis (OA) is serious and increasing in prevalence. Basic calcium phosphate (BCP) crystals are found in up to 70% of OA joints, and are uniquely associated with the disease. They are not found in other forms of arthritis such as rheumatoid arthritis, and they represent a potential therapeutic target in OA. There is no analytical procedure available to diagnose the presence of BCP crystals.


The short-term goal of this project is to devise a reliable, unambiguous and objective method that can detect these crystals in synovial fluid samples and then to develop a simple assay for the clinic that would enable identification and at least semi-quantitation of BCP crystals in samples from OA patients.

The development of this method will improve diagnosis of OA and will enable us to study the crystals to gain a better understanding of the disease itself, and to aid the investigation of new candidate drugs. The long-term goal of this research is to use these techniques to better characterise these crystals, further our understanding of the disease, and facilitate the development of novel drug therapies. Our Hypothesis is that crystals represent a potential therapeutic target for OA.

 

Efficacy of Methotrexate on Chronic Calcium Pyrophosphate Dihydrate (CPPD) Deposition Disease (chondrocalcinosis)

Principal Investigator :Prof Geraldine McCarthy  

 

Chondrocalcinosis is very common and occasionally severe metabolic arthropathy due to Calcium pyrophosphate dihydrate (CPPD) deposition. Recurrent and chronic CPPD arthropathies can lead to major joint destruction, sometimes very rapidly. There is currently no specific treatment to prevent or slow CPPD deposition, and the treatment of the resulting inflammation is very often disappointing, particularly in recurrent or chronic cases. In addition these agents very frequently induce intolerable side effects, particularly in the patients most frequently affected by chondrocalcinosis (elderly).

 

More importantly, none of these treatments proved able to stop gradual joint damage due to chondrocalcinosis. Low dose methotrexate is a potent anti-inflammatory agent, considered the gold standard therapy for many inflammatory arthritides. Given its good safety profile and its exceptionally low cost, it might represent an excellent therapeutic option also in chondrocalcinosis, particularly in patients resistant to classic treatments. In addition, methotrexate might slow and possibly prevent joint deterioration due to the disease. In the light of our preliminary experience, we hypothesized that methotrexate is efficient in controlling symptoms and signs of chronic chondrocalcinosis.

 

Study of Fibrinogen as a Marker of Disease Activity in Polymyalgia Rheumatica (PMR).

Principal Investigator: Prof Geraldine McCarthy


Polymyalgia rheumatica (PMR) is a common inflammatory disease affecting elderly persons. It is characterised by proximal muscle pain, raised acute phase markers and a rapid response to corticosteroids. Traditionally erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have been used as markers of disease activity and response to steroid therapy. However a number of studies have shown that ESR is not always significantly elevated in patients with PMR impeding assessment of disease activity and response to treatment (Proven et al, J Rheumatol 2000), (Martinez-Taboada et al, Clin Exp Rheumatol 2000).

 

ESR is influenced by several factors including fibrinogen. Fibrinogen has been shown to be superior to ESR in assessing disease activity in rheumatoid arthritis (Arvidson et al, Scand J Clin Lab Invest, 2002). Our department has previously demonstrated the usefulness of fibrinogen as a marker of disease activity in PMR in a retrospective study (Quillinan et al, 2005) and we now wish to re-evaluate this in a prospective study. Our aim is to demonstrate that fibrinogen is a more sensitive and specific marker of disease activity than ESR in the diagnosis and treatment of PMR.

 

Anti-MCV & Anti-CCP in RA

An observational study of the modified citrullinated vimentin anti-body (anti-MCV) the anti-cyclic-citrullinated peptide antibody (anti-CCP) status on the management of Irish patients with early rheumatoid arthritis.

Principle Investigator: Prof Geraldine McCarthy


Rationale: The poor prognosis associated with early and destructive RA, and the benefit of aggressive treatment strategies, has lead to an emphasis on early diagnosis and aggressive treatment regimens incorporating a TNF inhibitor.

A key challenge in the management of patients with RA is the early identification of patients that are at risk of developing a severe and destructive disease. A better understanding of prognostic factors such as anti-CCP, which is used in routine care, and the evaluation of new biomarkers such as anti-MCV, individually and in combination with other clinical parameters, is therefore needed in order to better identify patients with early RA that are at risk of developing aggressive diseases.

 

At the present time the prevalence of anti-MCV in an Irish RA population is unknown. A second challenge in the management of RA patients is the determination of the best treatment strategy tailored to individual patient’s needs. In routine practice, treatment approaches are based on the patient history and the availability of clinical parameters, such as a positive anti-CCP status, which is associated with worst prognostics. Consequently, the proposed study will provide data on the prevalence of anti-MCV in an Irish RA population and the use of anti-CCP and other clinical parameters currently used in routine care. In addition, the present study will evaluate the impact of the known anti-CCP status on patients’ management.

 

The results from the present study will have significant implications not only for individual patient but also from the societal perspective, since it will enhance the overall understanding and applications of different treatment approaches based on individual patients’ profile.

Research Area | Cancer

The Prostate Cancer Research Consortium

Principal Investigator:  Prof.  William Watson & Prof. John Fitzpatrick 

The Prostate Cancer Research Consortium (PCRC) (http://pcrc.tchpc.tcd.ie), was established in 2003, bringing together clinicians, pathologists, scientists, research nurses and allied health care professionals with a common goal of understanding the molecular and cellular basis for prostate cancer development and progression and the stated aim of translating this information to  improve detection, prognosis and treatment of this common disease. The PCRC was created under the Dublin Molecular Medicine Centre, now Molecular Medicine Ireland (http://www.dmmc.ie), and was successful  in competitive peer review in obtaining a Programme Grant from  Irish Cancer Society in 2003. This grant enabled the creation of the PCRC Bioresource, a collection of  clinically annotated biospecimens (tumour and normal biopsy tissue, blood, serum, urine, paraffin embedded tissue, nucleic acids) which provides the critical material for the research projects of the programme. This Core Grant was renewed after international peer review in 2007.

Membership of PCRC: Currently, the consortium includes four clinical sites;  Mater Misericordiae University Hospital, St James’s Hospital, Adelaide & Meath incorporating the National Children’s Hospital and Beaumont Hospital and four research institutions; UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin;  Institute of Molecular Medicine, Trinity College Dublin; RCSI-Education and Research Centre, Royal College of Surgeons in Ireland and National Centre for Sensor Research, Dublin City University.

Focus of Research:

The PCRC has undertaken a focus of research which aims to (i) identify novel cancer biomarkers which will permit early diagnosis of disease, provide critical information for risk stratification and clinical intervention (ii) determine potential targets and new approaches to kill prostate cancer cells. A comprehensive approach, utilising genomic, transcriptomic and proteomic platforms is underway to interrogate the PCRC Bio-resource and identify novel biomarker candidates. This data underpins focussed research projects, in both early detection and disease progression, to better identify individual patient groups who would benefit from specific treatment strategies, while also informing the experimental manipulation of malignant cells, leading to potential novel therapeutic entities and approaches.

The Prostate Cancer Research Consortium Bio-resource:

The Bioresource: The PCRC has established a multi-site or “Federated” prostate cancer bio-resource at its hospital sites following ethical approval by each of the hospital’s ethics committees. Using the federated collection model, agreed standard operating procedures are implemented across the different sites by dedicated research nurses (informed consent, sample collection and initial processing) ensuring uniformity of the resource. Samples are stored at the collection centres using monitored storage facilities as part of the Clinical Research Centres/Research Institutes, developed as part of Molecular Medicine Ireland through the Programme of Research for Third Level Institutions. The Bio-resource currently has 487 tissue samples with corresponding serum, plasma and DNA isolated from blood samples and 269 urine samples. Comprehensive clinical information is also collected for each patient and their samples including full pathology of the initial biopsy and radical prostatectomy, pre and post PSA and subsequent follow up of the patient.

The Bioresource Information and Management System: Central to the federated collection is the Bioresource Information and Management System (BIMS) architecture, which accommodates the collection and tracking of samples and integration of clinical information. The BIMS web based system stores all the de-identified data from the patients and their samples. This allows investigators to identify what samples are available and where they are located, as well as linking the relevant clinical data in a completely confidential way. The Consortium’s BIMS, developed in collaboration with the Trinity Centre for High Performance Computing (TCHPC) (www.tchpc.tcd.ie) and the company SlidePath (www.slidepath.com) is the first database that has been approved and licensed by the Data Protection Commissioner and fully complies with all National and European regulations. The Bio-resource and BIMS are monitored by the Bio-resource Management and Implementation Committee (see Figure) which also reviews access to the resource.

Linkages to International Bioresources: The current resource represents significant numbers of samples for biomarker discovery and first phase validation which would include the establishment and testing of appropriate technologies for further large scale validation. However larger bio-resources are required for the large scale validation of appropriate biomarkers. For this reason, the PCRC has established a number of international collaborations. These include: Prof  Helmut Klocker - University of Innsbruck and the Tyrol Prostate Cancer Screening programme (www.urolab-ibk.at), Prof David Horsfall – Australian Prostate Cancer Bio-Resource  (www.apccbioresource.org.au), Dr Sudhir Srivastava Early Detection Research Network (EDRN) of the National Cancer Institute (edrn.nci.nih.gov).

The consortium is also part of the International Cancer Biomarker Consortium–   www.fhcrc.org/science/international_biomarker/teams established by Professor Lee Hartwell. Currently negotiations are underway with Prof Coleen Nelson Queensland University of Technology, Institute of Health and Biomedical Innovation, Princess Alexandra Hospital, Brisbane, to establish an Australian-Irish Alliance in Prostate Cancer similar to the Australian-Canadian Prostate Cancer Research Alliance (http://www.accessibility.com.au/news/canadaaustralia-prostate-cancer-alliance-launched). In addition, the Consortium has a number of active international research collaborations, including the National Cancer  Institute (Dr Karen Woodson, Dr Mike Emmert Buck) and the UC Davis Cancer Centre (Prof Ralph DeVere White).  

Gastrointestinal Cancer Research Programme.

Principal Investigators: Dr David Murray and Prof. Padraic MacMathuna

Tumour progression beyond the primary site represents the most lethal aspect of cancer.  Our team is therefore focussed on identifying and understanding the biological mechanisms that drive the metastatic progression of gastrointestinal cancers.  At the CRC we avail of our close connection with gastrointestinal clinics at the hospital site to obtain patient tissue and biomaterials, thereby ensuring our studies are biomedically relevant and truly translational.  We have employed a variety of laboratory techniques to scrutinise the molecular biology of these diseases including microarray analysis, cell culture models and real time PCR.  For example, using patient tissue we have identified enhanced levels of the NET1 protein in gastric cancer.  

NET1 normally controls the motility of healthy cells, however in the tumour setting it NET1 drives tumour cell invasion, a key hallmark of metastatic cells.  Our group has shown that if we remove NET1 from cancer cells we inhibit the invasive capacity of these cells. As a potent mediator of the spread of cancer, NET1 is therefore of important clinical and therapeutic significance.  Our ongoing efforts into understanding NET1 biology will ultimately inform the development of a therapy targeting NET with the aim of reducing tumour metastasis and therefore cancer mortality. Our studies have led to the publication and presentation of our data in and at international peer-reviewed journals and meetings respectively.  We maintain a strong educational aspect to our programme with 5 MD fellows and 5 summer students having completed their research in our lab over the past 3 years. 

Bladder Cancer Research Programme

Principal Investigators: Dr. Amanda McCann & Prof. John Fitzpatrick

Urothelial cell carcinoma of the bladder (UCB), presentations can be stratified into non-invasive PTa and PT1 tumours, or as invasive/metastatic PT2, PT3 and PT4 cancers.  PTa and PT1 patients, have an unpredictable disease progression associated with their biology with some patients remaining disease free, while others develop invasive disease with subsequent multiple recurrencies.

Our bladder cancer research initiatives are specifically focused on identifying epithelial mesenchymal transition (EMT) markers predictive of invasive tumours.  One of the genes we are primarily interested in is alpha-t-catenin/(CTNNA3), which is down-regulated in EMT, and catenin undergoes not only loss of heterozygosity (LOH) but also altered imprinting, termed gain of imprinting (GOI), data currently being resubmitted to the British Journal of Cancer (BJC).

Lung Cancer Bioresource

Principal Investigators; Prof. Michael Keane & Dr Peter Doran

Over a million people die every year due to lung cancer.  Lung cancer is the leading cause of cancer death in Ireland and accounts for over 25% of new cancer cases. Our group are currently performing over 200 lung cancer resections annually at St Vincent’s University Hospital. We propose to establish a biorepositery consisting of lung tissue, blood and clinical data from these patients.  We envisage this resource to be of utmost value for developing our translational lung cancer research programme thereby allowing us to identify the molecular mechanisms underpinning this deadly disease.  By establishing such a bioresource thereby enabling us to perform top class research we will be able to translate our research findings to clinic thereby improving patient outcomes

Lung cancer is a hetrogenous disease that can be broadly sub divided into two groups; small cell lung carcinoma and non-small cell lung carcinoma.  We are interested in studying all subtypes and will therefore aim to collect material from patients in both groups.  Non-small cell lung carcinomas (NSCLC) include both squamous cell and adeno-carcinomas.  Small cell lung carcinomas (SCLC) originate in neuroendocrine cells, are generally more responsive to therapy than NSCLC however they often present late and therefore characterised by high metastatic potential.   SCLC incidence correlate closely with heavy smoking habits.

The establishment of a lung cancer biobank at St Vincents university Hospital will enable our group to lead the way for translational lung cancer research in Ireland.  It will enable us to answer clinically relevant questions which have to date remained unanswered.  

  • Can we obtain a better understanding of the molecular evolution of the disease ? 
  • Can we predict which patients will respond positively to therapy ? 
  • Can we develop robust biomarkers of lung cancer ? 

Furthermore this approach will allow us to evaluate new therapeutic approaches using ex vivo tissue. Material will be collected from lung cancer patients undergoing bronchoscopies and lung resections.  Material will be collected and stored securely at our biobank facility at the UCD Clinical Research Centre at St Vincent’s University Hospital.Paravertebral Anaesthesia and Cancer Recurrence

Principal Investigator: Dr. Donal Buggy

A Paravertebral Anaesthesia and Cancer Recurrence multicentre,international, prospective, randomised, controlled clinical study

Dr. Donal Buggy is Principal Investigator and local site director of the international RCT "Effect of regional anaesthesia during primary breast cancer surgery on breast cancer recurrence and metastases," (Registered trial # NCT (US) 00418457). This is a multicentre, international, prospective, randomised, controlled clinical study in which The Mater including the UCD CRC collaborates with the world No.1 most successful research consortium in perioperative medicine, Outcomes Research Consortium, lead by Prof. Daniel Sessler, Cleveland Clinic.

This group has 12 N Engl J Med, Lancet or JAMA publications in the past 12 years, and it represents a considerable achievement for Dr. Buggy and The Mater that this consortium has embraced our ideas and is focused on addressing this intruiging clinical question. Drs. Buggy and Sessler have submitted multiple grant applications based on this trial, and on experimental, translational research investigating potential mechanisms of the effects of anaesthetic drugs and techniques on breast cancer cell function.

Research Area | Ophthalmology

Retinal Transplant Programme

Principal Investigator;  Mr. David Keegan PhD; MB BCh BAO; MMedSc (Anat); FRCSI(Oph); FRCOphth

“Investigating donor cell survival strategies in cell-based therapies”

The Retinal Transplant Programme based at the UCD Clinical Research Centre aims to investigate the immunological consequences of retinal transplantation: one of the most promising potential therapies for currently incurable human retinal disorders such as age-related macular degeneration and retinitis pigmentosa. Retinal transplantation is a cell-based therapy that involves placing cells (such as retinal pigmented epithelium or stem cells) into the subretinal space at the back of the eye with the aim to replace or protect dying host cells.

The group is exploring strategies to prolong transplanted cell survival and comprises two full time scientific staff at the CRC (Dr T. Holmes and Dr D. Wallace) and ophthalmic clinicians based at the Mater Misericordiae University Hospital (K. Kennelly enrolled with UCD for a PhD in retinal transplantation immunology). It is currently funded by a Health Research Board project grant; “Mechanisms of early cell loss in retinal transplantation”. We believe that two mechanisms by which cells may be dying are by the action of the innate immune system and secondly a type of programmed cell death called apoptosis. Investigations are currently underway to investigate the role of the innate immune system and apoptotic cell death in retinal transplantation with the aim to reduce or prevent cell loss by a therapeutic approach.

With current emphasis on transplantation approaches to all basic science research we have applied and are soon to be ratified as one of the european clinical trial network (EVI.CT.SE) sites (the only one in the Republic of Ireland). This will enable us to conduct multi-site ophthalmic clinical trials within a unified Europe-wide framework.

Core areas: Retina, Retinal pigmented epithelium biology, Retinal transplantation, Innate immunity in the retina, Apoptosis in the retina, Retinal image analysis.

Research Area | Neurology

North Dublin Population Stroke Study

Principal Investigator: Prof Peter Kelly

  • North Dublin Population Stroke Study
  • North Dublin TIA Study
  • Dublin Carotid Atherosclerosis and Stroke Study (DUCASS)

The Neurovascular Clinical Science Unit at the Mater CRC conducts a range of patient-focused studies aimed at improving our ability to identify patients at high risk for disabling stroke, allowing us to better prevent stroke in these individuals. The North Dublin Stroke Study and North Dublin TIA Study are collaborativere search projects involving doctors at the Mater, Beaumont and Connolly Hospitals, North Dublin GPs, the Irish College of General Practitioners, and UCD.

Co-ordinated from the UCD Mater Clinical Research Centre, more than 750 Irish stroke patients have volunteered to provide medical and blood test information so that the research team can best identify who is at high risk for stroke."This research demonstrates the powerful advantages of combining a state-of-the-art health research facility with the expertise of teams of doctors working together in the hospitals and community" says Prof Peter Kelly,Consultant Neurologist, UCD and Mater Hospital, who leads the North DublinPopulation Stroke Study.

"The study will directly improve health services for Irish stroke patients by informing the National Stroke Strategy. It will also allow us to better prevent stroke by identifying patients at high risk and targeting treatment to these patients to prevent stroke from happening". The DUCASS Study aims to use modern imaging techniques such as PET, high-resolution MRI, and transcranial doppler ultrasound, blood biomarkers, and careful patient characterisation and follow-up to identify patients with TIA and minor stroke due to acutely-inflamed 'vulnerable' atherosclerotic plaque in the carotid artery. It is hoped that this approach will lead to an improved understanding of which patients are most at risk for early disabling stroke, and may provide surrogate biological markers to measure the effect of new treatments to prevent stroke in these high-risk patients.

Research Area | Musculoskeletal

Principal Investigators: 

  • Mr. Kevin Mulhall
  • Prof. Damian McCormack
  • Post-Doctoral Researcher: Dr. Pauline Walsh

The Musculoskeletal Research group at the UCD Clinical Research Centre employs the expertise of both scientists and clinicians to investigate key issues at the forefront of musculoskeletal medicine. The research carried out by the group has four major themes:

Project 1: Ischaemic preconditioning in total knee arthroplasty

Ischaemic preconditioning refers to a phenomenon whereby if a tissue is subjected to a short period of ischaemia, it is subsequently more adapted to tolerating a prolonged ischaemic insult. It has particular clinical relevance to ischaemia-reperfusion injury in orthopaedics. At the UCD CRC, our research focuses on understanding the molecular mechanisms associated with ischaemic preconditioning. We have recently conducted a trial of ischaemic preconditioning in a total knee arthroplasty population and are now developing a model of ischaemic preconditioning for in vitro investigation.

  • Principle Investigator: Mr. Kevin Mulhall
  • Researchers: Dr. Terence Murphy, Dr. Paul Magill and Dr. Pauline Walsh

Project 2: Effects of thromboprophylaxis on bone metabolism

Thromboprophylaxis is an effective treatment for the prevention of venous thromoembolism after major orthopaedic surgery. However, despite its many advantages, the long term use of certain thromboprophylactic agents has been linked to adverse effects on the skeleton, including osteoporosis. Our research is aimed at identifying the molecular mechanisms responsible for this bone loss.

  • Principle Investigator: Mr. Kevin Mulhall
  • Researchers: Dr. Gandhi Solayer and Dr. Pauline Walsh

Project 3: Osteoarthritis and inflammation

Osteoarthritis is a degenerative joint disease affecting millions worldwide and is predicted to affect many more as the world’s population ages. The development of this disease is multifactorial with mechanical as well as genetic influences playing a role. Osteoarthritis is not considered a classical inflammatory arthropathy, however, it is well associated with symptoms of joint swelling, pain and warmth. Investigations currently underway focus on the role of inflammatory cytokines in the progression of osteoarthritis.

  • Principle Investigator: Mr. Kevin Mulhall
  • Researchers: Dr. Joe Baker and Dr. Pauline Walsh

Project 4: Aseptic osteolysis - role of macrophages and potential therapies

Aseptic loosening is one of the major causes for failure of total joint arthroplasty, and accounts for up to 75% of revision surgeries. Osteolysis, the main cause of aseptic loosening, is generally accepted to be the result of an adverse inflammatory response to particle wear debris. Macrophages are thought to be the primary cellular initiators of this response. Current investigations are aimed at the identification of pharmacological agents for the suppression of this inflammatory response.

  • Principle Investigator: Prof. Damian McCormack
  • Researcher: Dr. Kingsley Chukwunyerenwa, Dr. Pauline Walsh

Research Area | Dermatology

Principle Investigator: Prof. Frank Powell FRCPI 

  • Post Doctoral Researcher: Dr. Noreen Lacey
  • MD: Dr. Siona O’ Reilly

Our team is primarily interested in investigating the pathogenesis of rosacea, a chronic inflammatory dermatosis. The aetiology of this skin condition is unknown. It is particularly common in Ireland, affecting 13% of the Irish adult population. This condition afflicts the centro-facial area of patients and can cause significant physical and psychosocial disturbances. Requiring sustained antibiotic treatment to clear, with an unknown mode of action, our aim is to provide further insight to this chronic facial disorder through our research here at the CRC and ultimately to provide improved therapeutic options to rosacea patients.  A possible aetiological agent is the ubiquitous Demodex mite. Our team were one of the first groups to describe the dramatic increase in Demodex mite numbers in rosacea patients compared to control subjects.

Normal individuals show no visible reaction to these mites but the histopathology of skin biopsies taken from rosacea patients shows inflammation centred around the follicles in which Demodex reside. Our research aims to elucidate the role of Demodex and their related bacteria, in the biology of the skin and to determine their pathogenic potential in the pathogenesis of rosacea and other skin disorders. Presently our investigations are focusing on:

  1. Characterising the facial milieu in rosacea patients. Aspects of this study are being performed in collaboration with Dr. Lorraine Brennan at the UCD Conway institute.
  2. Creating an in vitro environment to study the bioactivity of Demodex mites and the effects of therapeutic anti-microbial agents on these. This work is being carried out in association with Prof. Fiona Watt (Cancer research,UK Cambridge Research Institute), Prof. Christos Zouboulis (Dermatology and Immunology,Dessau Medical Centre, Germany) and Dr. Rory Breathnach (UCD Veterinary Clinic).
  3. Establishing the spectrum of Demodex –related bacterial flora in humans and dogs and their sensitivity to therapeutic anti-microbial agents.