Three important clinical research projects led by academic clinicians in the School of Medicine, Trinity College Dublin have emerged as winners in the recently announced Science Foundation Ireland (SFI) Frontiers for the Future programme. The awards will enable the generation of new knowledge with the long term impact of solving major health problems faced by our society, while also providing a continuum of support to retain our top research talent.
The three awardees will investigate improved care and treatment pathways for significant health challenges including: Inflammatory Bowel Disease (Dr Patrick Walsh), Type 2 diabetes (Dr Mikel Egaña) and preterm infant sepsis and brain injury (Prof. Eleanor Molloy).
More detail on each new award under the programme are outlined below.
SFI Frontiers for the Future Awards 2023 Project details:
- Title of Research Project Identifying the mechanism of action of a novel therapeutic target during the earliest phases of IBD onset in childhood
Name, Title of Lead PI
Dr Patrick Walsh, Associate Professor in Paediatric Immunology, Clinical Medicine/National Children’s Research Centre, CHI Crumlin
Inflammatory Bowel Disease (IBD) is an inflammation or swelling in the gastrointestinal tract. IBD is a life-long chronic intestinal inflammatory condition comprising of separate disease types known as ulcerative colitis (UC) and Crohns disease (CD) which are increasingly being first diagnosed during childhood.
While many new treatment options have emerged over the past 20 years there remains a substantial number of patients for whom these approaches are ineffective. Moreover, our understanding of how disease develops during its earliest phases - when therapeutic intervention will likely be most beneficial - is relatively poor.
Lead Principal Investigator Dr Patrick Walsh, Associate Professor in Paediatric Immunology, Clinical Medicine/National Children’s Research Centre, CHI Crumlin and his team will uncover precisely how a new target pathway for IBD mediates the initiation of disease during childhood.
The team’s research is aimed at uncovering new mechanisms which underlie the earliest phases of onset of IBD among children. The study will place paediatric patients at its core and underscore efforts to improve treatment options for children and facilitate better outcomes for what is currently a life-long debilitating disease.
The project brings together an international collaborative and translational research enterprise including partners from academic, paediatric hospital and pharmaceutical drug development backgrounds, allowing efforts to be expedited to improve treatment options for children.
Project collaborators include Dr Seamus Hussey, CHI Crumlin and Dr Darren Ruane, Janssen.
Speaking about the award, Dr Walsh said:
“This award provides us with the opportunity to continue to grow our understanding of the reasons why some children are affected with IBD and to ultimately contribute towards improving options for the treatment of this debilitating disease.”
- Title of Research Project Cerebrovascular dynamic responses subsequent to highintensity
interval vs moderate-intensity continuous training in men and women with type 2 diabetes
Name, Title of Lead PI
Dr Mikel Egaña, Associate Professor in Physiology , School of Medicine
Exercise training is well-recognised as an effective strategy to prevent cardiovascular and brain related disorders in typical patients, but less is known about what the optimal exercise is to ensure good brain health for patients with type 2 diabetes (T2D). Type 2 diabetes occurs when blood sugar levels are too high due to insufficient insulin production or when the insulin that is produced by the pancreas gland is not working effectively.
Now a research study, led by Dr Mikel Egaña (Physiology), will help determine optimal exercise training protocols for cerebrovascular function in type 2 diabetes, potentially contributing to improved therapeutics and clinical interventions designed to help restore decreased cerebrovascular function. Dr Egaña is one of two newly announced recipients of the SFI Frontiers of the Future awards. The SFI Frontiers for the Future Programme provides opportunities for independent investigators to conduct highly innovative, collaborative research with the potential to deliver impact, whilst also providing opportunities for high-risk, high-reward research projects.
People with type 2 diabetes (T2D) have an increased risk for the development of cardiovascular disease, dementia and Alzheimer’s disease than people without T2D. Alongside little information on the optimal exercise for good brain health, the benefits of exercise training on the cerebrovasculature in T2D are not well understood.
Raising cerebrovascular blood flow by exercise is associated with cardiorespiratory fitness, brain beta amyloid load and executive function in healthy older individuals, making the understanding of this information vital. As a result the team will examine the effectiveness of different intensity-specific aerobic exercise training protocols on brain circulation (measured by middle-cerebral artery blood flow) and cognitive function in men and women T2D.
By quantifying the magnitude of the cerebrovascular blood flow changes subsequent to exercise training this research will lay the foundations to alter the trajectory for the neurodegenerative disease in this population. This could be achieved by delaying or preventing potential stroke, cognitive decline and/or dementia in this high-risk population, bestowing corresponding benefits upon their families, the healthcare system and society.
This study is a collaboration with Dr Mikel Egaña, Department of Physiology at the School of Medicine and the following expert team:
- Dr Norita Gildea, Department of Physiology, School of Medicine
- Prof Donal O’Shea, St Columcille's Hospital; St Vincent’s University Hospital and University College Dublin.
- Prof Sandra Billinger, Kansas University Medical Center.
- Prof David Poole, Kansas State University.
Speaking about the research, Dr Egaña said:
“This research will help determine optimal exercise training protocols for cerebrovascular function in type 2 diabetes, serving to develop therapeutics to improve brain health.” - Title of Research Project
Preterm infant immunomodulation to treat sepsis and brain injury prevention (PLATYPUS)
Name, Title of Lead PI
Professor Eleanor Molloy, Professor of Paediatrics & Child Health, Paediatrics
Dept of Paediatrics, School of Medicine, Trinity College Dublin, Consultant Neonatologist & Paediatrician at the Coombe Women and Infant’s University Hospital & Children’s Health Ireland.
Preterm birth is the world's leading cause of death in children under 5 years. Preterm infants have a high risk of infection due to alterations in their immune system that are not completely understood. Inflammation is the body's normal response to infection and although it is essential for resolving infections, when uncontrolled it can cause damage to the body. In preterm infants infections and inflammation in the intestine (necrotising enterocolitis) can result in brain injury. We study new ways to predict outcome and responses to treatment, looking to help parents with planning healthcare needs for their baby.
Preterm delivery has a huge global impact and the incidence is increasing with long-lasting health effects with deteriorating outcomes. Improved counting of preterm births, and related outcomes, is a priority of the Every Newborn Action Plan, led by UNICEF and WHO, and will be crucial to achieving national Sustainable Development Goals (SDGs) to end preventable new-born and child deaths by 2030. We are aiming to contribute towards improving the accuracy and timely diagnosis of sepsis in neonates using immunological biomarkers as predictors of outcomes, and exploring potential immunodulatory medications. We also aim to improve educational materials and communication with parents and families regarding management of preterm sepsis, Necrotizing enterocolitis (NEC) and longer-term follow-up by developing a consensus neonatal sepsis definition. The end goal is a standardised care and collaboration as seen in adult and paediatric sepsis which will ultimately improve neurodevelopmental outcomes.
Collaborators
- Dr. Paul Downey, Consultant Pathologist, National Maternity hospital
- Dr. Anne Doolan, Director of Paediatrics, Coombe Women’s and Infant’s University Hospital
- Prof. Tobias Strunk, Consultant Neonatologist, The University of Western Australia
- Dr. Ann Hickey, Director of Neonatology, Children Health Ireland (CHI) at Crumlin and Temple Street
- Prof. Sri Paran, Consultant Paediatric Surgeon, Children Health Ireland (CHI) at Crumlin
- Dr. Arthur White, Assistant Professor in Statistics and Optimization, Trinity College Dublin
- Ms. Mandy Daly, Director of Advocacy and Policy Making, Irish Neonatal Health Alliance
- Prof. Camilla Martin, Prof. of Paediatrics, Harvard Medical School
- Prof. Afif El-Khuffash, Consultant Neonatologist, Children Health Ireland (CHI) at Temple Street
Speaking about the award, Professor Molloy said:
“This award gives us the opportunity to work with parents and international collaborative partners in the USA and Australia to improve outcomes for babies born preterm and at risk of neurodevelopmental problems.”