Research Undertaken in the MFRL at TUH
Respiratory Microbiome and antimicrobial resistance research.
Prof Julie Renwick, an Assistant Professor and Head of Discipline of Clinical Microbiology in TCD leads research on respiratory infections and the lung microbiome primarily in people with cystic fibrosis (CF). CF is a life-shortening inherited disorder with a hallmark of chronic airway infections. The leading cause of mortality in CF is lung infections. The lungs of people with CF harbour many bugs at one time, and this is called polymicrobial (many bugs) or a 'microbiome'. Dr Renwick leads a number of projects studying these airway microbiomes in CF. She is also leading research on the global crisis of antimicrobial resistance (AMR).
Studies running in Dr Renwick’s group:
- The AIrway Microbiome in CF (AIM CF) project employs next generation sequencing to explore the diversity of bugs present in the airways of people with CF.
- The Study of Polymicrobial INteractions in CF (SPIN-CF), managed by postdoctoral scientist Dr Emma Reece, aims to understand the complex communications between bugs in the microbiome (yes bugs talk to each other!) and how this may influence disease.
- RESIST-AMR, a cross-school collaborative PhD programme taking One Health approaches to fighting the global health threat of AMR.
- Co-PI on the recently awarded HORIZON-MSCA-2021 project ‘Stop Bag Bugs’ exploring antimicrobial activity of novel compounds.
- Contributor to the international Pfizer Antimicrobial Testing Leadership and Surveillance (ATLAS) project.
These projects are funded by the Wellcome Trust, the Irish Research Council, TCD PhD Provost award, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Prendergast challenge-based award and HORIZON-MSCA-2021.
Dr Renwick is the director of the MSc in Healthcare Infection for the School of Medicine and hosts MSc research projects for this course in the MFRLs.
Helicobacter Pylori Infection & Antibiotic Resistance Research
During the year, Dr. Sinead Smith (Ussher Assistant Professor in Applied & Translational Medicine, TCD) and Professor Deirdre McNamara (Consultant Gastroenterologist, TUH and Associate Professor, TCD) initiated a nationwide research project on Helicobacter pylori (H. pylori) antibiotic resistance.
H. pylori is a bacterium (germ) that infects the stomach of approximately half of the world’s population. Although infection does not usually have serious consequences, some patients will develop stomach inflammation, ulcers or stomach cancer. Treatment has become challenging in recent years due to antibiotic resistance. Dr. Smith and Professor McNamara received an Applied Partnership Award from the Health Research Board to investigate the prevalence of H. pylori antibiotic resistance in patients attending different hospitals around the country. Laboratory aspects of the project are carried out at the state-of-the-art Meath Foundation Research Laboratory on the TUH campus.
It is anticipated that information from this research will be used to guide doctors in the most appropriate antibiotic combinations for the successful treatment of H. pylori.
The Efficacy and Safety of Psilocybin Therapy in Treatment Resistant Depression
Over the last two decades there has been a renewed interest in the therapeutic potential of psychedelics, such as psilocybin, the main component of magic mushrooms. Promising early studies showed that psilocybin, when administered with psychological support and under psychiatric supervision could lead to improvements in mood, anxiety and quality of life. These studies prompted large scale clinical trials of psilocybin therapy for treatment resistant depression (TRD).
Dr John Kelly and Professor Veronica O’Keane in TUH and TCD were among the site investigators in the international trial of psilocybin therapy for TRD, which began three years ago. Results from the trial, funded by COMPASS pathways were released this year. This trial of 233 participants, showed that psilocybin therapy at the higher dose of 25mg resulted in a significant improvement in depression, anxiety and quality of life. It also showed that the higher dose of 25mg was superior to 10mg and 1mg.
Dr. John Kelly and Professor Veronica O’Keane, together with a site in San Diego, also conducted the first ever study examining the efficacy and safety of psilocybin therapy in TRD in people who choose to remain on their SSRI antidepressant. This study of 19 people showed that psilocybin (25mg) therapy could also lead to significant improvements in depression in those taking SSRI antidepressants. Taken together, these studies will pave the way for a world-wide phase 3 clinical trial of psilocybin therapy for TRD in 2022 to determine whether psilocybin therapy will be approved as a much-needed additional treatment strategy for those who suffer from depression.
An expansion of psilocybin therapy research into other mental health disorders and an exploration of the potential therapeutic role of short acting psychedelics, such as Dimethyltryptamine therapy are also planned in the near future.
Research to Define Key pathways that predispose to chronic inflammatory diseases
The Donnelly Research group led by Professor Seamas Donnelly seeks to define key regulatory pathways that predispose to chronic inflammatory diseases such as Asthma, Pulmonary Fibrosis, COPD and Rheumatoid Arthritis.
Their work undertaken at the Meath Foundation Research Laboratory epitomises Translational Medicine where original bench based observations are translated to clinical disease.
They are particularly interested in:
▪ Development of novel compounds as anti-inflammatory/anti-cancer therapies
▪ Host environmental influences on the regulation of the inflammatory response
▪ Genetic profiling guiding disease diagnosis, prognosis and response to therapy
▪ Host/Pathogen interactions which predispose towards more aggressive infection
▪ How the faecal microbiome influences host immune responses
▪ Mitcochondrial stress and chronic inflammatory diseases
▪ Stem cell dysregulation in Long-COVID Syndrome
They use advanced cell and molecular biology techniques, in vitro and in vivo models to address these questions. It is their vision that this work will pave the way for specific tailored therapies which would attenuate key regulatory pathways in inflammatory diseases.
Ultrasound-Guided Biopsy Programme
Professor Ronan Mullan is a Clinical Associate Professor with Trinity College Dublin and Consultant Rheumatologist at TUH. In 2016, Professor Mullan established a translational ultrasound-guided biopsy programme at TUH through which he collaborates at both national and international level.
Professor Mullan’s research, which is carried out in the Meath Foundation Research Laboratory, focuses on understanding the mechanisms of action of inflammatory arthritic diseases such as Rheumatoid Arthritis and Gout. Currently Professor Mullan’s research group is assessing the role of NLRP3 inflammatory pathways as well as the potent suppression of inflammation by a novel small molecule inhibitor on ex-vivo tissue samples and primary blood cells taken from Gout patients. Gout is an episodic destructive inflammatory arthritis, triggered by innate inflammatory responses to monosodium urate crystals. Gout affects 2% of adults and is now the leading cause of inflammatory arthritis within developed countries. This study could potentially lead to a clinical trial of MCC950 for the treatment of Gout.
Vascular Neurology Translational Research Group
Professor Dominick McCabe, Consultant Neurologist-Vascular Neurologist / Clinical Professor in Neurology at TUH/TCD is the Principal Investigator (PI) / Co-PI / Collaborator in several local, national and international multi-centre research studies or trials. His innovative translational research programme in stroke medicine and platelet science/haemostasis is led from the Meath Foundation Research Laboratory, TUH-TCD.
His Vascular Neurology Research group has conducted several original studies (e.g. the PACS, HEIST, TRAP, OATS and OATS-I pilot studies) which have shown that platelets may be excessively activated / hyper-reactive following TIA/ischaemic stroke, and that an important proportion of patients with ischaemic cerebrovascular disease are ‘poorly-responsive’ to commonly-prescribed antiplatelet agents with ‘high on-treatment platelet reactivity (HTPR)’ in the laboratory. They have also found an ongoing stimulus to increased platelet production and secretion, and enhanced platelet and endothelial activation and coagulation system potential after TIA/ischaemic stroke in patients with symptomatic compared with asymptomatic moderate-severe carotid stenosis, including in those who do not have micro-embolic signals (MES) on transcranial Doppler ultrasound. These data improve our understanding of the underlying biological mechanisms which may contribute to the disparity in the risk of TIA/stroke in subgroups of patients with recently symptomatic vs. asymptomatic carotid stenosis, and in subgroups of symptomatic patients with different plaque types and MES status.
He is the PI of the ‘Optimal Antiplatelet Therapy in TIA and Ischaemic Stroke-International (OATS-I) study’ which has been planned in collaboration with world-class, expert academic clinicians, platelet scientists, pharmacogenetics scientists, patient advocacy groups and patients, data scientists, industry researchers and health economists at 26 international centres. The OATS-I consortium aims to enable clinicians to prescribe more clinically-effective and cost-effective antiplatelet therapy to optimise protection against future vascular events, dementia and vascular death in individual patients following TIA or ischaemic stroke