Senior Research Fellow
Adelaide Medical School
Faculty of Health and Medical Sciences
I am a Senior Research Fellow and Co-Director of the Cystic Fibrosis Airway Research Group at the Women’s and Children’s Hospital in Adelaide.
My key achievements lie in the area of non-invasive synchrotron imaging of respiratory processes at scales that have not previously been possible in-vivo. I have developed a novel non-invasive airway health assessment method based on using synchrotron imaging to track changes in the mucociliary transit (MCT) behaviour of deposited marker particles following pharmaceutical treatments. In 2016 my collaborators and I published the first demonstration of the use of X-ray based pulmonary function testing for the quantification of lung disease heterogeneity in B-ENaC mice. This unique and world-leading imaging method gathers lung motion information during normal breathing, and has revolutionary potential since it can detect, quantify and follow changes in regional lung function over time.
In 2014 my group published key data to show that our airway conditioning and lentiviral gene vector system produces correction of the CFTR defect in CF mouse nasal airways for at least 12 months. This work was the first to show improved survival in the gene vector treated CF group, supporting the prediction that CF airway gene therapy can produce significant health benefits.
All of this work has built towards a world leading capacity to perform rapid, non-invasive, direct, quantitative measurement of the effects of CFTR gene therapy on airway health and lung function.
- My Research
- Grants and Funding
- Professional Activities
Functional Lung Imaging
There is growing recognition of the inadequacies of the two methods used for detecting and tracking CF lung disease progression: traditional lung function testing methods and structural imaging methods such as CT. Spirometry is a blunt instrument for measuring lung function, and “lumps” the good, bad and compensating lung regions into a few global numbers (eg FEV1). No accurate location information is available to direct targeted treatments, and spirometry cannot be performed by children under 6. Even with software analyses such as CF-CT and PRAGMA-CT, CT still has poor specificity and does not measure function; structural changes do not always predict function.
Localising and tracking disease and the effectiveness of pharmaceutical and genetic therapies in animal models and patients is essential. 4Dx has developed patented algorithms to calculate local lung function, using a combination of phase contrast X-ray imaging (PCXI) and velocimetry that track lung tissue motion, and detect abnormal airflow. This allows low dose, X-ray based, local airflow analysis, for application to physiology and disease-research questions.
CF is a major disease focus of 4Dx's development, however XV is applicable to ANY respiratory disorder. 4Dx have adult clinical trials underway and expect FDA approval mid 2019 for routine adult human lung function imaging. Subsidiary Notting Hill Devices now produces an animal scanner utilising this technology.
My team’s work was essential for 4Dx and Notting Hill Devices to develop their technology and to maintain a focus on CF. We helped build the foundation of airway imaging research using synchrotron PCXI. Our first paper established the utility of PCXI for airway imaging studies, and is now cited as one of the first in this area. We have provided assistance with the development of the 4Dx AccuVent 200 small animal ventilator.
In 2011 our first XV experiments on B-ENaC mice – a model of CF like lung disease – showed we could locate functional lung deficits correlated with lung function tests and histology. That paper is used by 4Dx as crucial validation of their technology now available commercially for small animals.
XV technology is set to have huge impact on diagnosis and tracking of respiratory disorders. The regional and time-resolved XV functional imaging allows regions of CF disease initiation to be identified early enough to start aggressive targeted treatment. For the first time, people with CF can receive truly preventative interventions, and reliable and accurate therapy assessments.
Date Position Institution name 2019 Research Leader Robinson Research Institute 2018 Senior Research Fellow University of Adelaide 2018 Career Development Fellow Robinson Research Institute 2016 - 2017 Affiliate Senior Lecturer University of Adelaide 2007 - 2017 Senior Medical Scientist Women's and Children's Hospital
Awards and Achievements
Date Type Title Institution Name Country Amount 2018 Fellowship Robinson Research Institute Career Development Fellowship University of Adelaide Australia — 2017 Award Translational Research Award Women's and Children's Health Network Service Excellence Awards Australia — 2013 Fellowship MS McLeod Postdoctoral Research Fellowship Women's and Children's Hospital Australia — 2009 Award Semi-finalist for Young Investigator Award Women's and Children's Hospital Australia —
Date Institution name Country Title 2002 - 2007 Flinders University Australia PhD 1997 - 2000 Flinders University Australia BSc 1997 - 2001 Flinders University Australia BEng (Biomedical) with Honours (First Class)
Year Citation 2018 Farrow, N., Cmielewski, P., Donnelley, M., Rout-Pitt, N., Bertoncello, I., & Parsons, D. (2018). Epithelial Disruption Enables Human Airway Stem Cell Transplantation in Mouse Nasal Airways. In MOLECULAR THERAPY Vol. 26 (pp. 79). Chicago, IL: CELL PRESS. 2018 Werdiger, F., Donnelley, M., Parsons, D., Morgan, K., Samarage, C., Carnibella, R., & Fouras, A. (2018). QUANTIFICATION OF REGIONAL LUNG DISEASE IN beta-ENAC MICE USING A LABORATORY X-RAY SOURCE. In PEDIATRIC PULMONOLOGY Vol. 53 (pp. 199). WILEY. 2018 McIntyre, C., Rout-Pitt, N., Donnelley, M., & Parsons, D. (2018). LOBE SPECIFIC TARGETING OF LENTIVIRAL VECTOR GENE TRANSFER TO THE LUNGS OF ADULT RATS. In PEDIATRIC PULMONOLOGY Vol. 53 (pp. 218). WILEY. 2018 McIntyre, C., Cmielewski, P., Craig, F., Rout-Pitt, N., Parsons, D., & Donnelley, M. (2018). CF-RELATED PATHOLOGIES ARE MORE SEVERE IN KNOCKOUT RATS COMPARED TO PHE508DEL RATS. In PEDIATRIC PULMONOLOGY Vol. 53 (pp. 218). WILEY. 2018 Gradl, R., Dierolf, M., Hehn, L., Gunther, B., Kutschke, D., Yang, L., . . . Morgan, K. (2018). Dynamic x-ray imaging at the Munich Compact Light Source. In Microscopy and Microanalysis Vol. 24 (pp. 350-351). Saskatoon, Canada: Cambridge University Press (CUP).
2017 Jung, H., Lee, I., Lee, S., Parsons, D., & Donnelley, M. (2017). Multiple mucociliary transit marker tracking in synchrotron X-ray images using the global nearest neighbor method. In Proceedings of the 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC' 17) Vol. 2017 (pp. 1824-1827). Piscataway, NJ: IEEE.
2016 Donnelley, M., Morgan, K., Farrow, N., Siu, K., & Parsons, D. (2016). Non-invasive airway health measurement using synchrotron X-ray microscopy of high refractive index glass microbeads. In M. DeJonge, D. Paterson, & C. Ryan (Eds.), AIP Conference Proceedings Vol. 1696 (pp. 4 pages). Australian Synchrotron, Melbourne, AUSTRALIA: AMER INST PHYSICS.
DOI Scopus3 WoS3
2012 Morgan, K., Paganin, D., Parsons, D., Donnelly, M., Yagi, N., Uesugi, K., . . . Siu, K. (2012). Single grating x-ray imaging for dynamic biological systems. In International Workshop on X-Ray and Neutron Phase Imaging with Gratings Vol. 1466 (pp. 124-129). United States: Springer New York LLC.
DOI Scopus2 WoS2
2010 Donnelley, M., Parsons, D., Morgan, K., & Siu, K. (2010). Animals In synchrotrons: overcoming challenges for high-resolution, live, small-animal imaging. In K. Siu (Ed.), Proceedings of 6th International Conference on Medical Applications of Synchrotron Radiation Vol. 1266 (pp. 30-34). United States: American Institute of Physics.
DOI Scopus13 WoS11
2009 Morgan, K., Paganin, D., Parsons, D., Donnelley, M., Yagi, N., Uesugi, K., . . . Siu, K. (2009). Optimising coherence properties for phase contrast x-Ray imaging (PCXI) to reveal airway surface liquid (ASL) as an airway health measure. In IFMBE Proceedings Vol. 25 (pp. 135-138). Munich, Germany: Springer Verlag.
DOI Scopus2 WoS1
2008 Donnelley, M., Knowles, G., & Hearn, T. (2008). A CAD system for long-bone segmentation and fracture detection. In A. Elmoataz, O. Lezoray, F. Nouboud, & D. Mammass (Eds.), IMAGE AND SIGNAL PROCESSING Vol. 5099 (pp. 153-162). Cherbourg-Octeville, FRANCE: SPRINGER-VERLAG BERLIN.
2005 Donnelley, M., & Knowles, G. (2005). Automated Bone Fracture Detection. In Proceedings of SPIE - The International Society for Optical Engineering Vol. 5747 (pp. 955-966). San Diego: Society of Photo-optical Instrumentation Engineers (SPIE).
2002 Gopalakrishnan, D., McLennan, G., Donnelley, M., Delsing, A., Suter, M., Flaherty, D., . . . Reinhardt, J. (2002). Color analysis of the human airway wall. In Proceedings of SPIE - The International Society for Optical Engineering Vol. 4683 (pp. 341-351). San Diego: Society of Photo-optical Instrumentation Engineers (SPIE).
Year Citation 2018 Donnelley, M., & Parsons, D. (2018). HOW DO WE KNOW IF CYSTIC FIBROSIS LUNG GENE THERAPY WORKS? THE IMPORTANCE OF THE RIGHT ANIMAL MODEL, AND THE RIGHT MEASUREMENT METHOD. Poster session presented at the meeting of JOURNAL OF GENE MEDICINE. Univ Technol Sydney, Sydney, AUSTRALIA: WILEY. 2018 Carpentieri, C., Farrow, N., Mcintyre, C., Cmielewski, P., Rout-Pitt, N., Parsons, D., & Donnelley, M. (2018). COMPARATIVE EFFICIENCY OF HA AND VSV-G PSEUDOTYPED LENTIVIRAL VECTORS FOR CYSTIC FIBROSIS AIRWAY GENE THERAPY. Poster session presented at the meeting of RESPIROLOGY. WILEY. 2018 Farrow, N., Cmielewski, P., Donnelley, M., Bertoncello, I., & Parsons, D. (2018). DOES EPITHELIAL ABLATION IN THE NASAL AIRWAYS OF MICE IMPROVE STEM CELL ENGRAFTMENT?. Poster session presented at the meeting of RESPIROLOGY. WILEY. 2017 McCarron, A., Rout-Pitt, N., McIntyre, C., Donnelley, M., & Parsons, D. W. (2017). Lentivirus Production in Stirred-Tank and Packed-Bed Basket Bioreactor Systems: A Comparison. Poster session presented at the meeting of MOLECULAR THERAPY. Washington, DC: CELL PRESS. 2017 Farrow, N., Donnelley, M., Rout-Pitt, N., McIntyre, C., Bertoncello, I., & Parsons, D. W. (2017). High Efficiency In Vitro Transduction of Human Airway Basal Cells. Poster session presented at the meeting of MOLECULAR THERAPY. Washington, DC: CELL PRESS. 2016 Donnelley, M., Morgan, K., & Parsons, D. (2016). DIRECT X-RAY MEASUREMENT OF AIRWAY SURFACE HEALTH IN ANIMAL MODELS: AN UPDATE ON THE STATE-OF-THE-ART. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY-BLACKWELL. 2015 Kicic, A., Ling, K., Martinovich, K., Garratt, L., Looi, K., Kicic-Starcevich, E., . . . Moodley, Y. (2015). CORRECTIVE EFFECTS ON AIRWAY EPITHELIAL FUNCTION BY HUMAN AMNIOTIC EPITHELIAL CELLS (HAEC) WHEN TREATING CYSTIC FIBROSIS. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY-BLACKWELL. 2015 Cmielewski, P., Parsons, D., Donnelley, M., Padmanabhan, H., Ling, K., Stick, S., . . . Moodley, Y. (2015). DELIVERY OF HUMAN AMNIOTIC STEM CELLS CORRECTS CFTR FUNCTION IN CF MOUSE NASAL AIRWAYS IN VIVO. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY-BLACKWELL. 2014 Farrow, N., McQualter, J., Donnelley, M., Bertoncello, I., & Parsons, D. (2014). GENE THERAPY FOR CF: IS LONG TERM EXPRESSION A CONSEQUENCE OF TRANSDUCING CONDUCTING AIRWAY ENDOGENOUS RESPIRATORY STEM CELLS?. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY-BLACKWELL. 2012 Donnelley, M., Siu, K., Morgan, K., & Parsons, D. (2012). HIGH FRAME RATE IMAGING OF NASAL FLUID DOSING DYNAMICS. Poster session presented at the meeting of RESPIROLOGY. WILEY-BLACKWELL. 2012 Morgan, K., Donnelley, M., Fouras, A., Parsons, D., & Siu, K. (2012). SYNCHROTRON PHASE CONTRAST X-RAY IMAGING CAN DETECT AIRWAY SURFACE LIQUID DEPTH CHANGES FOLLOWING AEROSOLISED HYPERTONIC SALINE TREATMENT. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY-BLACKWELL. 2012 Siu, K., Chua, C., Donnelley, M., Morgan, K., Farrow, N., Mall, M., . . . Fouras, A. (2012). REGIONAL MEASURES OF LUNG FUNCTION IN THE beta-ENAC MOUSE OBTAINED USING X-RAY IMAGING VELOCIMETRY. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY-BLACKWELL. 2009 Donnelley, M. W., Morgan, K., Fouras, A., Skinner, W., Uesugi, K., Yagi, N., . . . Parsons, D. W. (2009). Individual particulate mucociliary transit analysis using synchrotron X-ray imaging. Poster session presented at the meeting of Abstracts of the 23rd Annual North American Cystic Fibrosis Conference, as published in Pediatric Pulmonology. Minneapolis, Minn.: Wiley-Liss.
As CF Airway Research Group Co-Director, I worked with A/Prof David Parsons to grow my team from 1 RA in 2007 to 5 Postdocs, 2 RA’s and 4 PhD students in 2019. David retains his SA Health clinical role, managing the Women's and Children's Hospital lung function lab. We have a successful partnership with me as the lead full-time researcher driving the research programme.
I have had success with Cat 1, small grant, and philanthropic funding over the last 10 years, with $2.6 M awarded in the last 2 years (2.5x the previous 2), demonstrating rapid growth in research status and success enabling substantial team growth. My large grants include:
2019 N. Farrow, M. Donnelley, A. Jaffe, D. Parsons, S. Waters, Orphan Disease Center Pilot Grant: “Airway Cell Therapy for Cystic Fibrosis Nonsense Mutations”, $73,000
2019-22 D. Parsons, M. Donnelley, K. Morgan, R. Boucher, T. Kuchel, NHMRC Project Grant: “Translating cystic fibrosis gene-addition therapy for use in human lungs: Demonstrating efficacy, safety and scalability”, $861,345
2019 N. Rout-Pitt, N. Farrow, J. Delhove, D. Parsons, M. Donnelley, WCH Foundation Grant: “Cell plasticity of the airways: Understanding the stem cell niche to optimise gene therapy and stem cell targeting”, $75,000
2019 J. Delhove, M. Donnelley, N. Farrow, D. Parsons, WCH Foundation Grant: “Designing immune-stealth, antiphagocytic targeting vectors for cystic fibrosis lentiviral gene therapy”, $75,000
2019 N. Farrow, M. Donnelley, P. Cmielewski, J. Delhove, D. Parsons, Channel 7 Childrens Research Foundation Grant: “Can neonatal exposure improve the effectiveness of cystic fibrosis gene therapy re-dosing?”, $34,625
2018-19 D. Parsons, M. Donnelley, M. Kitchen, K. Morgan, G. Zosky, J. Breen, USA CF Foundation Grant: “Lentiviral CFTR gene-addition in CF rat lungs: Effect of PA infection, safety and efficacy”, $282,491
2018-19 M. Donnelley, D. Parsons, Gandel Philanthropy Major Grant (via the Cure 4 CF Foundation): “An Australian gene therapy designed to cure CF lung disease: pre-clinical development of an essential, game-changing new lung health measurement technique”, $166,000
2018 M. Donnelley, Robinson Research Institute Career Development Fellowship, $50,000
2018 M. Donnelley, N. Farrow, P. Cmielewski, A. McCarron, D. Parsons, WCH Foundation Grant: “Effective re-dosing protocols for lasting cystic fibrosis lentiviral airway gene therapy”, $75,000
2017–18 D. Parsons, M. Donnelley, Fay Fuller Discovery Project Grant (via the Cure 4 CF Foundation): “Can in vivo delivery of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene soon after birth prevent the establishment and / or progression of Cystic Fibrosis (CF) lung disease?”, $670,292
2017 N. Farrow, M. Donnelley, P. Cmielewski, D. Parsons, WCH Foundation Grant: “Quantifying lentiviral mediated gene expression for cystic fibrosis lung disease in normal rat lungs”, $72,975
2017 C. McIntyre, D. Parsons, M. Donnelley, P. Cmielewski, Channel 7 Childrens Research Foundation Grant: “Gene therapy for cystic fibrosis”, $34,412
2017 M. Donnelley, C. McIntyre, N. Rout-Pitt, A. McCarron, D. Parsons, Channel 7 Childrens Research Foundation Grant: “Improving the efficiency of cystic fibrosis airway gene therapy”, $74,213
2016–18 D. Parsons, I. Bertoncello, M. Donnelley, R.Boucher, T. Kuchel, NHMRC Project Grant 1098127: “Identifying the role of airway stem cells in maintaining lentiviral mediated gene expression for cystic fibrosis lung disease”, $814,272
2015 M.Donnelley, K. Morgan, D. Parsons, A. Fouras, I. Lee, WCH Foundation Grant: “Next generation non-invasive airway surface health assessment: Combined surface hydration and mucus clearance analysis for CF treatment development”, $67,824
2015–17 D. Parsons, A. Fouras, J. Li, K. Siu, R. Boucher, K. Morgan, M. Donnelley, M. Kitchen, NHMRC Project Grant 1079712: “Revolutionising the diagnosis and monitoring of CF lung disease”, $792,778
2014 M.Donnelley, D. Parsons, A. Juhasz, E. Smith, K. Morgan, K. Siu, WCH Foundation Grant: “Lead air-pollution in children: Airway surface behaviour of inhaled particles and influence on blood levels”, $69,687
2013–16 M. Donnelley, MS McLeod Postdoctoral Fellowship: “Uptake of inhaled lead: Description and modelling of deposition, and determinants of vascular uptake”, $310,000
2012 M.Donnelley, D. Parsons, K. Siu, A. Fouras, K. Morgan, WCH Foundation Grant: “Understanding the clearance of inhaled lead dust in the conducting airways using synchrotron imaging”, $43,754
2011 D. Parsons, A. Fouras, K. Siu, S. Hooper, M. Donnelley, Australian Cystic Fibrosis Research Trust Grant: “Localised detection of early stage CF disease via quantitative imaging of lung motion”, $110,749
2010–12 D. Parsons, K. Siu, M. Donnelley, W. Skinner, NHMRC Project Grant 626863: “Synchrotron X-ray assessment of airway surface physiology for cystic fibrosis”, $765,702 (Score of 7)
2009 D. Parsons, M.Donnelley, K. Siu, N. Yagi, M. Kitchen, WCH Foundation Grant: “Dynamic synchrotron x-ray detection of individual pollutant particle behaviour after deposition onto live airways”, $54,360
I am passionate about ensuring students and ECR’s get the best start to their research career. I co-coordinate the Robinson Research Institute (RRI) mentoring program.
In my team I drive targeted EMCR career mentoring, providing regular encouragement, support, and direction that is often overlooked, particularly in the current uncertain medical research funding environment. I connect them to leading groups, providing travel to labs at: JASRI (Japan); UNC, UPenn and Cedars-Sinai (USA); Imperial College (UK); Monash and the IMBL.
As a primary/secondary supervisor, I encourage active student involvement in grant and paper writing, and submission processes, with one student (A McCarron) listed as a CI on two recent grants, as well receiving the 2019 CFA Anne Maree Bosch ECF. I encourage my students to be involved in the 3 min thesis competition; one (H Padmanabhan) represented UofA at the national level. Four of my Honours students have published their work and gone on to PhD’s, and 1 is now an MD (J Penny-Dimri) continuing to publish in CF.
Current Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2018 Co-Supervisor Lentiviral Mediated Airway Gene Therapy: Is Iysophosphatidylcholine required for safe and effective gene transfer in a cystic fibrosis lung? Doctor of Philosophy Doctorate Full Time Ms Chantelle Lee Carpentieri 2016 Co-Supervisor Development of up-scaled lentiviral production and purification methods for large animal and human use in cystic fibrosis airway gene therapy. Doctor of Philosophy Doctorate Full Time Miss Alexandra Sarah Ann Mc Carron
Date Role Membership Country 2018 - ongoing Member American Society of Gene and Cell Therapy United States 2018 - ongoing Member Australian and New Zealand Society of Respiratory Science Australia 2001 - ongoing Member Institute for Electrical and Electronic Engineers United States
Connect With Me