Supervisor View Full Details 2nd

• genetics, genomics and molecular biology
• infectious disease and the immune system
• cell and developmental biology/regenerative medicine
• physiology and non-communicable disease

• Medicine
• Paediatrics
• Pathology

• Adolescent medicine
• Infectious diseases
• Immunology
• Neonatology
• Pharmacology
• Physiology
• Respiratory Medicine

Research in my group focuses principally on the cellular and molecular biology of innate immune mechanisms in the lung, particularly in cystic fibrosis and alpha-1 antitrypsin deficiency. I have a particular interest in non-coding RNA expression and function and lead a group that are developing inhaled molecular therapies. Another major aspect of my research is the investigation of the molecular mechanisms underlying sex differences in disease in adults and neonates - this work, to date, has concentrated on studying the effects of estrogen and the contribution of X chromosome-encoded genes and microRNAs.

1: McKiernan PJ, Molloy KP, Cryan SA, McElvaney NG, Greene CM. X Chromosome-encoded MicroRNAs Are Functionally Increased in Cystic Fibrosis Monocytes. Am J Respir Crit Care Med. 2018 Mar 1;197(5):668-670.

2: O'Driscoll DN, De Santi C, McKiernan PJ, McEneaney V, Molloy EJ, Greene CM. Expression of X-linked Toll-like receptor 4 signaling genes in female vs. male neonates. Pediatr Res. 2017 May;81(5):831-837.

3: Greene CM, Marciniak SJ, Teckman J, Ferrarotti I, Brantly ML, Lomas DA, Stoller JK, McElvaney NG. α1-Antitrypsin deficiency. Nat Rev Dis Primers. 2016 Jul 28;2:16051.

4: Chotirmall SH, Smith SG, Gunaratnam C, Cosgrove S, Dimitrov BD, O'Neill SJ, Harvey BJ, Greene CM, McElvaney NG. Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis. N Engl J Med. 2012 May 24;366(21):1978-86.

Potential PhD projects available in my group for which the appropriate expertise, infrastructure and national/international and industrial collaborations exist include, but are not limited to, combinations of the following types of studies:

- Biomarker discovery and identification of altered gene and noncoding RNA expression patterns associated with infection, non-infectious disease, disease severity, prescribed medications etc. [qPCR; TaqMan miRNA assays; miRScript arrays; Open Array, Nanostring or ArrayStar profiling; Next generation sequencing]

- Functional studies of miRNA and lncRNA [in silico bioinformatics analysis, qPCR, western blotting/ELISA, overexpression and knock down studies, luciferase reporter assays, cloning & site-directed mutagenesis, miR-CATCH, in situ hybridisation, immunohistochemistry, chromatin immunoprecipitation, promoter methylation studies, in vitro translation, cDNA arrays].

- Evaluation of estrogenic or X chromosome-mediated effects on disease susceptibility, disease progression or response to treatment.

- Generation of nanoparticles encapsulating miRNA-, lncRNA-, gene-, or protein-targeting therapeutics (e.g. locked nucleic acid-based oligos, siRNAs, peptides/proteins) to treat the inflammatory or other manifestations of disease.

- Characterisation of the toxicity and efficacy of these drugs in in vitro cell models and iPSCs (induced pluripotent stem cells) by specialised single target [qPCR, ELISA, Western Immunoblotting, Confocal Microscopy, Flow Cytometry] and high throughput methodologies [Mesoscale Discovery arrays, High Content Analysis, Mass Spectrometry].

- Evaluation of a drug's nebulisation compatibility and airway deposition properties via cascade impactor and breathing mannequin studies.