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Full NameDr Cian O'Leary
Department:School of Pharmacy and Biomolecular Sciences
Organisation:Royal College of Surgeons in Ireland
- cell and developmental biology/regenerative medicine
- physiology and non-communicable disease
- bioengineering/medical devices
- Respiratory Medicine
The O'Leary Lab is focused on discovering and developing new treatments for chronic diseases with cell-matrix dysregulation at the centre of their pathogenesis. To this end, Dr O'Leary's lab focuses on developing novel disease models of 3D cell environments that mimic diseased tissue in the body in order to identify unexplored, druggable targets for which medicinal products can be designed and formulated to strategically strike these targets for the ultimate aim of improving clinical outcomes in chronic disease.
Major research themes include:
- Mechanopharmacology: Understanding mechanobiology in disease to develop pharmacological agents that target cell-matrix interactions.
- Tissue engineered 3D in vitro models of epithelial interfaces and biological barriers.
- Drug formulation of new treatments to prevent or reverse fibrosis.
- Drug repurposing through novel formulation development.
- Respiratory tissue regeneration and medical device development.
Chronic conditions of interest include:
- Lung cancer (NSCLC).
- Pancreatic cancer (PDAC).
- Idiopathic pulmonary fibrosis and interstitial lung disease.
- Cystic fibrosis.
For a full list of publications, please visit Dr O'Leary's Google Scholar profile at https://scholar.google.com/citations?user=hh7EbuwAAAAJ&hl=en.
Despite the encouraging clinical impact provided by recently-approved anti-fibrotic drugs, idiopathic pulmonary fibrosis (IPF) persists as a devastating disease that requires new therapies to reduce its significant morbidity and mortality within 3-5 years of diagnosis. Although IPF pathogenesis is incompletely understood, a central component is dysregulated intercellular communication between epithelial, fibroblast, and immune cells within the lung microenvironment, resulting in excessive extracellular matrix (ECM) deposition by myofibroblasts that aberrantly remodel alveoli with excessive, fibrotic matrix, and loss of respiratory function. Accordingly, anti-fibrotic drugs target lung fibroblasts to reduce disease progression. However, outstanding questions remain about their benefit for reducing mortality. Furthermore, current drugs frequently induce debilitating gastrointestinal adverse effects such as nausea and diarrhoea that are difficult to tolerate, emphasising the critical need for novel, inhaled therapeutics that avoid systemic adverse drug side effects or drug-drug interactions in addition to eliciting enhanced site-specific disease-modifying action.
In parallel with the need for new therapies, pathophysiologically-relevant human disease models of IPF are warranted to accurately evaluate anti-fibrotic efficacy. Current preclinical in vitro cell models fail to recapitulate the contribution of ECM that influences a range of cell behaviours; for IPF, changes in the composition and physical properties of the lung tissue can influence pro-fibrotic signalling to exacerbate disease progression, with possible modulation on pharmacological action of a novel therapeutic. Thus, it is paramount to not only develop new medicines for the treatment or improved management of IPF, but also to utilise organotypic cell models that exhibit the key features of the human pathophysiology for more relevant and robust preclinical data prior to animal testing and human trials.
Examples of PhD projects could fall into each of these pathways, either focusing on respiratory drug development in translational projects, or the development of bioengineered models to address fundamental research questions about pathophysiology.