Dr Chantal Donovan

Dr Chantal Donovan

Conjoint Fellow

School of Biomedical Sciences and Pharmacy

Opening up an interest in airways

An undergraduate job in a lab over winter sparked a career focus on lung disease Dr Chantal Donovan’s move to a world-leading respiratory medicine research centre in Newcastle.

Dr Chantal Donovan

Chantal can pinpoint her interest in science as being sparked in high school so she decided to enrol in a Bachelor of Science at the University of Melbourne to help hone her focus. It was while studying pharmacology in her second year, that Chantal found her passion.

Not just content with knowing that drugs worked, Chantal ended up majoring in pharmacology and biochemistry because “I wanted to fully understand how the drugs worked,” Chantal says.

It was during her third year of study that Chantal met a pivotal force in her research: Dr Jane Bourke. “Jane took me on as a winter student and we did a great deal of work into asthma models that really set me on my research path.” Chantal ended up doing honours, and then a PhD with Jane looking at novel therapies for asthma and COPD.

When Jane moved universities, Chantal found a new supervisor, Associate Professor Ross Vlahos who was working with COPD research and smoke models. “I ended up moving what I’d learnt with Jane into Ross’s models and the two ended up combining nicely.”

And this research has continued to inspire Chantal’s work. “We were looking at two different drugs and their impact on airways. The first was rosiglitazone, a drug used for treating type II diabetes which we found actually had an effect relaxing the airways. The second was working with the bitter taste receptors on the tongue. We found that not only are these receptors in the airways, but the drugs that work on them can work to relax the muscle too.

Chantal has already published a substantial body of work, with 18 peer reviewed publications and 25 abstracts as 1st/last author. Her work on understanding the pathogenesis of lung disease, identifying novel targets and therapeutics has been recognised by at the Thoracic Society of Australia and New Zealand and the Australasian Society of Clinical Pharmacologists and Toxicologists society meetings.

A prestigious British Pharmacological Society/ASCEPT Outstanding Young Investigator Award and an array of competitive grants, visiting fellowships and travel awards are testament to Chantal’s standing in the field. Chantal was invited to session chair at the 2016 European Respiratory Society Annual Scientific Meeting in London, and has been a reviewer for a range of journals.

Finding world class facilities in Newcastle

An early career researcher, Chantal has been extremely busy since submitting her PhD in August 2015. The move to Newcastle was considered: Chantal knew she wanted to work with a lung-research lab – so she set about researching the best. And this search led her to the renowned work of Professor Phil Hansbro and his research team. “Of all the labs I’ve looked at in the world, none compares to Phil’s,” Chantal enthuses. “It was quite an easy decision to come here to be honest.”

Before moving from Melbourne, Chantal applied for an NHMRC Early Career Fellowship to work with Phil’s team exploring lung diseases and potential new treatments and preventions. Lung diseases are a major burden on the Australian population and economy. With this work, the team will assess the potential of a new target (IL-33) and therapy (anti-IL-33) in suppressing remodelling in experimental models and human tissues.

Thanks to the success of this application, this work will be a continuation of some of the work that Chantal explored for her PhD “It’s a nice trajectory really,” she adds.

Chantal’s work into IL-33 will explore the role that this protein plays in a number of viral infections and inflammation of the lung. “We know it’s involved, but what’s unknown is how it affects ‘airway remodelling’ which is the scarring of the tissue that you get over time with lung disease.”

“We do know that when you have reduced remodelling you also have reduced IL-33, so what we’re trying to do is understand how and why this happens and whether we can use this information to target the remodelling.”

This work has potential applications for a whole range of lung diseases such as asthma, COPD and IPF. “Remodelling is currently untreated in a whole range of different diseases, so hopefully we can find a link that we can then target.”

Sharing science with parliament

Passionate about raising the profile of science, Chantal attended Science Meets Parliament in Canberra in March 2017. This bi-partisan annual event has been held since 1999 with the aim of urging “all political parties to recognise the importance of science to the nation’s future; economically, socially, culturally and environmentally”.

Chantal was thrilled to have the opportunity to put her respiratory research before the nation’s political leaders. “This event showcases scientific research across all aspects of STEM and provides opportunities to raise issues about the future of research in Australia.”

“By bringing together scientists and politicians, it provides a platform to bridge the gap in knowledge, in particular the needs and concerns of scientists at a government level, with the ultimate goal raising the profile of science in Australia.

“During the meeting I had the honour of meeting the Australian of the Year Emeritus Professor Alan Mackay-Sim and the Honorable Bill Shorten and this two day meeting really provided an eye-opening experience.”

Ensuring that research into lung diseases is effectively funded is a focus on Chantal’s, who acknowledges that science communications and outreach is just another item on a researcher’s to-do list.

Australia has one of the highest rates of lung disease in the world, with one in ten Australians living with a respiratory illness. Chantal’s aim is to help identify gaps in our knowledge which will start to help us identify new therapeutic targets and biomarkers. Watch this space.

Dr Chantal Donovan

Opening up an interest in airways

A job in a lab over winter sparked a career focus on lung disease Dr Chantal Donovan’s move to a world-leading respiratory medicine research centre.

Read more

Career Summary

Biography

Dr Donovan is an NHMRC Early Career Post-doctoral Fellow (Peter Doherty Biomedical Fellow) for the Priority Centre for Healthy Lungs and School of Biomedical Science and Pharmacy. She is a member of Professor Phil Hansbro's research team based at the Hunter Medical Research Institute. She completed her PhD (January 2012-April 2015) in the Department of Pharmacology and Therapeutics at the University of Melbourne and Bachelor of Science (Honours) with first class at the University of Melbourne. She completed her first postdoctoral training (April 2015-December 2016) in the Department of Pharmacology at Monash University, with additional training under precision cut lung slice expert Professor Michael Sanderson at the University of Massachusetts Medical School in the USA. 

Dr Donovan has 19 peer reviewed publications (13 manuscripts, 6 reviews). She has presented 25 abstracts as 1st/last author and 15 co-author at 13 national & 7 international conferences. 

Her research on understanding the pathogenesis of lung disease, identifying novel targets and new therapeutics, is recognised by prestigious oral (x7) and poster (x7) awards at the national respiratory (Thoracic Society of Australia and New Zealand)  and pharmacological (Australasian Society of Clinical Pharmacologists and Toxicologist) society meetings. Including the prestigious British Pharmacological Society/ASCEPT Outstanding Young Investigator Award (2016), finalist in the Young Investigator Award (TSANZ, 2014), and the Garth McQueen oral presentation prize for best PhD student (ASCEPT, 2012).

She has obtained over $500k in competitive grants/fellowships, including equipment grants, visiting fellowships, prestigious national (University of Melbourne, UoN) and international (American Thoracic Society, ATS) travel awards, and an international trainee scholarship from the ATS (2016).

Dr Donovan is an expert in a range of mouse models (allergic, bacterial, viral, cigarette smoke) of respiratory disease, assessment of lung function (whole lung mechanics, DLCO, large airway organ bath, small airway myography, precision cut lung slices), and molecular biology (PCR, Western blot, ELISA). She played an integral role in extending the standard outcomes of PCLS in Australia including integrated assessment of molecular signaling pathways and cytokine release.


Qualifications

  • Doctor of Philosophy, University of Melbourne
  • Bachelor of Science (Honours), University of Melbourne

Keywords

  • COPD
  • airway remodelling
  • asthma
  • precision cut lung slices

Fields of Research

Code Description Percentage
110203 Respiratory Diseases 100
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (34 outputs)

Year Citation Altmetrics Link
2020 Ali MK, Kim RY, Brown AC, Donovan C, Vanka KS, Mayall JR, et al., 'Critical role for iron accumulation in the pathogenesis of fibrotic lung disease.', J Pathol, 251 49-62 (2020)
DOI 10.1002/path.5401
Citations Scopus - 10Web of Science - 8
Co-authors Liz Milward, Jay Horvat, Philip Hansbro, Alexandra Brown, Jemma Mayall
2020 Lo Bello F, Hansbro PM, Donovan C, Coppolino I, Mumby S, Adcock IM, Caramori G, 'New drugs under development for COPD.', Expert Opin Emerg Drugs, 1-13 (2020)
DOI 10.1080/14728214.2020.1819982
Co-authors Philip Hansbro
2020 Ali MK, Kim RY, Brown AC, Mayall JR, Karim R, Pinkerton JW, et al., 'Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma.', Eur Respir J, 55 (2020)
DOI 10.1183/13993003.01340-2019
Citations Scopus - 1Web of Science - 2
Co-authors Jemma Mayall, Alexandra Brown, Philip Hansbro, Jay Horvat, Peter Wark, Paul Foster, Liz Holliday, Liz Milward, Malcolm Starkey
2020 Malyla V, Paudel KR, Shukla SD, Donovan C, Wadhwa R, Pickles S, et al., 'Recent advances in experimental animal models of lung cancer', FUTURE MEDICINAL CHEMISTRY, 12 567-570 (2020)
DOI 10.4155/fmc-2019-0338
Citations Scopus - 2
Co-authors Philip Hansbro
2020 Donovan C, Liu G, Shen S, Marshall JE, Kim RY, Alemao CA, et al., 'The role of the microbiome and the NLRP3 inflammasome in the gut and lung', Journal of Leukocyte Biology, 108 925-935 (2020)

©2020 Society for Leukocyte Biology The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one ... [more]

©2020 Society for Leukocyte Biology The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut¿lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut¿lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.

DOI 10.1002/JLB.3MR0720-472RR
Citations Scopus - 1Web of Science - 1
Co-authors Philip Hansbro
2020 Donovan C, Hansbro PM, 'IL-33 in Chronic Respiratory Disease: From Preclinical to Clinical Studies', ACS Pharmacology and Translational Science, 3 56-62 (2020) [C1]

Copyright © 2019 American Chemical Society. IL-33 has been deorphanized as a member of the IL-1 family and has key roles as an alarmin and cytokine with potent capacity to drive t... [more]

Copyright © 2019 American Chemical Society. IL-33 has been deorphanized as a member of the IL-1 family and has key roles as an alarmin and cytokine with potent capacity to drive type 2 inflammation. This has led to a plethora of studies surrounding its role in chronic diseases with a type 2 inflammatory component. Here, we review the roles of IL-33 in two chronic respiratory diseases, asthma and chronic obstructive pulmonary disease (COPD). We discuss the hallmark and paradigm-shifting studies that have contributed to our understanding of IL-33 biology. We cover animal studies that have elucidated the mechanisms of IL-33 and assessed the role of anti-IL-33 treatment and immunization against IL-33. We highlight key clinical evidence for the potential of targeting increased IL-33 in respiratory diseases including exacerbations, and we outline current clinical trials using an anti-IL-33 monoclonal antibody in asthma patients. Finally, we discuss some of the challenges that have arisen in IL-33 biology and highlight potential future directions in targeting this cytokine in chronic respiratory diseases.

DOI 10.1021/acsptsci.9b00099
Citations Scopus - 1
Co-authors Philip Hansbro
2020 Alemao CA, Budden KF, Gomez HM, Rehman SF, Marshall JE, Shukla SD, et al., 'Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders.', Allergy, (2020)
DOI 10.1111/all.14548
Co-authors Philip Hansbro, Simon Keely
2020 Johansen MD, Irving A, Montagutelli X, Tate MD, Rudloff I, Nold MF, et al., 'Animal and translational models of SARS-CoV-2 infection and COVID-19.', Mucosal Immunol, 13 877-891 (2020)
DOI 10.1038/s41385-020-00340-z
Citations Scopus - 1Web of Science - 1
Co-authors Philip Hansbro, Peter Wark, Nicole Hansbro
2020 Prihandoko R, Kaur D, Wiegman CH, Alvarez-Curto E, Donovan C, Chachi L, et al., 'Pathophysiological regulation of lung function by the free fatty acid receptor FFA4.', Sci Transl Med, 12 (2020)
DOI 10.1126/scitranslmed.aaw9009
Citations Scopus - 1Web of Science - 1
Co-authors Philip Hansbro
2019 Donovan C, Starkey MR, Kim RY, Rana BMJ, Barlow JL, Jones B, et al., 'Roles for T/B lymphocytes and ILC2s in experimental chronic obstructive pulmonary disease', Journal of Leukocyte Biology, 105 143-150 (2019) [C1]

©2018 Society for Leukocyte Biology Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however,... [more]

©2018 Society for Leukocyte Biology Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however, their specific roles in the pathogenesis of COPD are unclear. Therefore, we investigated the roles of T and B lymphocytes and group 2 innate lymphoid cells (ILC2s) in airway inflammation and remodelling, and lung function in an experimental model of COPD using mice that specifically lack these cells (Rag1 -/- and Rora fl/fl Il7r Cre [ILC2-deficient] mice). Wild-type (WT) C57BL/6 mice, Rag1 -/- , and Rora fl/fl Il7r Cre mice were exposed to cigarette smoke (CS; 12 cigarettes twice a day, 5 days a week) for up to 12¿weeks, and airway inflammation, airway remodelling (collagen deposition and alveolar enlargement), and lung function were assessed. WT, Rag1 -/- , and ILC2-deficient mice exposed to CS had similar levels of airway inflammation and impaired lung function. CS exposure increased small airway collagen deposition in WT mice. Rag1 -/- normal air- and CS-exposed mice had significantly increased collagen deposition compared to similarly exposed WT mice, which was associated with increases in IL-33, IL-13, and ILC2 numbers. CS-exposed Rora fl/fl Il7r Cre mice were protected from emphysema, but had increased IL-33/IL-13 expression and collagen deposition compared to WT CS-exposed mice. T/B lymphocytes and ILC2s play roles in airway collagen deposition/fibrosis, but not inflammation, in experimental COPD.

DOI 10.1002/JLB.3AB0518-178R
Citations Scopus - 14Web of Science - 12
Co-authors Philip Hansbro, Jay Horvat, Peter Wark, Malcolm Starkey, Paul Foster
2019 Caramori G, Ruggeri P, Mumby S, Ieni A, Lo Bello F, Chaminka V, et al., 'Molecular links between COPD and lung cancer: new targets for drug discovery?', Expert Opinion on Therapeutic Targets, 23 539-553 (2019) [C1]

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Introduction: COPD and lung cancer are leading causes of morbidity and mortality worldwide, and they sh... [more]

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Introduction: COPD and lung cancer are leading causes of morbidity and mortality worldwide, and they share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by their incidence in only a fraction of smokers. This reflects the ability of cigarette smoke to induce an inflammatory response in the airways of susceptible smokers. Moreover, COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage and repression of the DNA repair mechanisms, chronic exposure to pro-inflammatory cytokines, repression of innate immunity and increased cellular proliferation. Areas covered: We have focused our review on the potential pathogenic molecular links between tobacco smoking-related COPD and lung cancer and the potential molecular targets for new drug development by understanding the common signaling pathways involved in COPD and lung cancer. Expert commentary: Research in this field is mostly limited to animal models or small clinical trials. Large clinical trials are needed but mostly combined models of COPD and lung cancer are necessary to investigate the processes caused by chronic inflammation, including genetic and epigenetic alteration, and the expression of inflammatory mediators that link COPD and lung cancer, to identify new molecular therapeutic targets.

DOI 10.1080/14728222.2019.1615884
Citations Scopus - 6Web of Science - 6
Co-authors Philip Hansbro
2019 Donovan C, Hansbro PM, 'TRPA1: A potential target for cold-induced airway disease?', RESPIROLOGY, 24 193-194 (2019)
DOI 10.1111/resp.13453
Co-authors Philip Hansbro
2019 Starkey MR, Plank MW, Casolari P, Papi A, Pavlidis S, Guo Y, et al., 'IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis', EUROPEAN RESPIRATORY JOURNAL, 54 (2019) [C1]
DOI 10.1183/13993003.00174-2018
Citations Scopus - 8Web of Science - 7
Co-authors Philip Hansbro, Jay Horvat, Gerard Kaiko, Paul Foster, Nicole Hansbro, Malcolm Starkey, Peter Wark
2018 Terlizzi M, Molino A, Colarusso C, Donovan C, Imitazione P, Somma P, et al., 'Activation of the Absent in Melanoma 2 Inflammasome in Peripheral Blood Mononuclear Cells From Idiopathic Pulmonary Fibrosis Patients Leads to the Release of Pro-Fibrotic Mediators', FRONTIERS IN IMMUNOLOGY, 9 (2018) [C1]
DOI 10.3389/fimmu.2018.00670
Citations Scopus - 7Web of Science - 6
Co-authors Philip Hansbro
2018 Schofield ZV, Croker D, Robertson AAB, Massey NL, Donovan C, Tee E, et al., 'Characterisation of small molecule ligands 4CMTB and 2CTAP as modulators of human FFA2 receptor signalling', SCIENTIFIC REPORTS, 8 (2018) [C1]
DOI 10.1038/s41598-018-36242-1
Citations Scopus - 3Web of Science - 3
Co-authors Philip Hansbro
2017 Hansbro PM, Kim RY, Starkey MR, Donovan C, Dua K, Mayall JR, et al., 'Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma', Immunological Reviews, 278 41-62 (2017) [C1]

© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Severe, steroid-resistant asthma is clinically and economically important since affected individuals d... [more]

© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid-resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid-resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid-resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity-or pollution-associated asthma.

DOI 10.1111/imr.12543
Citations Scopus - 53Web of Science - 48
Co-authors Paul Foster, Jodie Simpson, Nicole Hansbro, Malcolm Starkey, Lisa Wood, Jay Horvat, Darryl Knight, Jemma Mayall, Philip Hansbro
2017 Jones B, Donovan C, Liu G, Gomez HM, Chimankar V, Harrison CL, et al., 'Animal models of COPD: What do they tell us?', Respirology, 22 21-32 (2017) [C1]

© 2016 Asian Pacific Society of Respirology COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mec... [more]

© 2016 Asian Pacific Society of Respirology COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.

DOI 10.1111/resp.12908
Citations Scopus - 54Web of Science - 56
Co-authors Darryl Knight, Philip Hansbro
2017 Liu G, Cooley MA, Nair PM, Donovan C, Hsu AC, Jarnicki AG, et al., 'Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c', JOURNAL OF PATHOLOGY, 243 510-523 (2017) [C1]
DOI 10.1002/path.4979
Citations Scopus - 30Web of Science - 28
Co-authors Darryl Knight, Hock Tay, Jay Horvat, Philip Hansbro, Alexandra Brown, Alan Hsu, Christopher Grainge, Paul Foster, Nicole Hansbro, Peter Wark
2016 Kim RY, Rae B, Neal R, Donovan C, Pinkerton J, Balachandran L, et al., 'Elucidating novel disease mechanisms in severe asthma', CLINICAL & TRANSLATIONAL IMMUNOLOGY, 5 (2016) [C1]
DOI 10.1038/cti.2016.37
Citations Web of Science - 19
Co-authors Malcolm Starkey, Philip Hansbro, Jay Horvat, Darryl Knight
2016 Thorburn AN, Tseng H-Y, Donovan C, Hansbro NG, Jarnicki AG, Foster PS, et al., 'TLR2, TLR4 AND MyD88 Mediate Allergic Airway Disease (AAD) and Streptococcus pneumoniae-Induced Suppression of AAD.', PLoS One, 11 e0156402 (2016) [C1]
DOI 10.1371/journal.pone.0156402
Citations Scopus - 17Web of Science - 17
Co-authors Nicole Hansbro, Peter Gibson, Paul Foster, Philip Hansbro
2016 Lam M, Royce SG, Donovan C, Jelinic M, Parry LJ, Samuel CS, Bourke JE, 'Serelaxin Elicits Bronchodilation and Enhances ß-Adrenoceptor-Mediated Airway Relaxation', Frontiers in Pharmacology, 7 406-406 (2016) [C1]
DOI 10.3389/fphar.2016.00406
Citations Scopus - 8
2016 Donovan C, Bourke JE, Vlahos R, 'Targeting the IL-33/IL-13 Axis for Respiratory Viral Infections', Trends in Pharmacological Sciences, 37 252-261 (2016) [C1]
DOI 10.1016/j.tips.2016.01.004
Citations Scopus - 17Web of Science - 17
2016 Faiz A, Donovan C, Nieuwenhuis MAE, van den Berge M, Postma D, Yao S, et al., 'Latrophilin receptors: novel bronchodilator targets in asthma', Thorax, (2016)
Citations Scopus - 6Web of Science - 6
2016 Royce SG, Nold MF, Bui C, Donovan C, Lam M, Lamanna E, et al., 'Airway remodeling and hyperreactivity in a model of Bronchopulmonary dysplasia and their modulation by IL-1 receptor antagonist', American Journal of Respiratory Cell and Molecular Biology, 55 858-868 (2016) [C1]
DOI 10.1165/rcmb.2016-0031OC
Citations Scopus - 17
2016 Donovan C, Seow HJ, Bourke JE, Vlahos R, 'Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to ß-adrenoceptor agonists in mouse precision cut lung slices', Clinical Science, 130 829-837 (2016) [C1]
DOI 10.1042/CS20160093
Citations Scopus - 10
2015 Donovan C, Bailey SR, Tran J, Haitsma G, Ibrahim ZA, Foster SR, et al., 'Rosiglitazone elicits in vitro relaxation in airways and precision cut lung slices from a mouse model of chronic allergic airways disease', American Journal of Physiology - Lung Cellular and Molecular Physiology, 309 L1219-L1228 (2015) [C1]
DOI 10.1152/ajplung.00156.2015
Citations Scopus - 13
2015 Donovan C, Seow HJ, Royce SG, Bourke JE, Vlahos R, 'Alteration of Airway Reactivity and Reduction of Ryanodine Receptor Expression by Cigarette Smoke in Mice', American Journal of Respiratory Cell and Molecular Biology, 53 471-478 (2015) [C1]
DOI 10.1165/rcmb.2014-0400OC
Citations Scopus - 10Web of Science - 11
2015 Donovan C, Royce SG, Vlahos R, Bourke JE, 'Lipopolysaccharide does not alter small airway reactivity in mouse lung slices', PLoS One, 10 (2015) [C1]
DOI 10.1371/journal.pone.0122069
Citations Scopus - 4
2014 Bourke JE, Bai Y, Donovan C, Esposito JG, Tan X, Sanderson MJ, 'Novel small airway bronchodilator responses to rosiglitazone in mouse lung slices', American Journal of Respiratory Cell and Molecular Biology, 50 748-756 (2014) [C1]

There is a need to identify novel agents that elicit small airway relaxation when ß2-adrenoceptor agonists become ineffective in difficult-to-treat asthma. Because chronic treatme... [more]

There is a need to identify novel agents that elicit small airway relaxation when ß2-adrenoceptor agonists become ineffective in difficult-to-treat asthma. Because chronic treatment with the synthetic peroxisome proliferator activated receptor (PPAR)¿ agonist rosiglitazone (RGZ) inhibits airway hyperresponsiveness in mouse models of allergic airways disease, we tested the hypothesis that RGZ causes acute airway relaxation by measuring changes in small airway size in mouse lung slices. Whereas the ß-adrenoceptor agonists albuterol (ALB) and isoproterenol induced partial airway relaxation, RGZ reversed submaximal and maximal contraction to methacholine (MCh) and was similarly effective after precontraction with serotonin or endothelin-1. Concentration-dependent relaxation to RGZ was not altered by the ß-adrenoceptor antagonist propranolol and was enhanced by ALB. RGZ-induced relaxation wasmimicked by other synthetic PPAR¿ agonists but not by the putative endogenous agonist 15-deoxy-PGJ2 and was not prevented by the PPAR¿ antagonist GW9662. To induce airway relaxation, RGZ inhibited the amplitude and frequency of MCh-induced Ca2+ oscillations of airway smooth muscle cells (ASMCs). In addition, RGZ reduced MCh-induced Ca2+ sensitivity of the ASMCs. Collectively, these findings demonstrate that acute bronchodilator responses induced by RGZ are PPAR¿ independent, additive with ALB, and occur by the inhibition of ASMC Ca2+ signaling and Ca2+ sensitivity. Because RGZ continues to elicit relaxation when ß-adrenoceptor agonists have a limited effect, RGZ or related compounds may have potential as bronchodilators for the treatment of difficult asthma. Copyright © 2014 by the American Thoracic Society.

DOI 10.1165/rcmb.2013-0247OC
Citations Scopus - 18
2014 FitzPatrick M, Donovan C, Bourke JE, 'Prostaglandin E

Background: Current asthma therapy may not adequately target contraction of smaller intrapulmonary airways, which are a major site of airway obstruction and inflammation. The aim ... [more]

Background: Current asthma therapy may not adequately target contraction of smaller intrapulmonary airways, which are a major site of airway obstruction and inflammation. The aim of this study was to characterise responses of mouse intrapulmonary airways to prostaglandin E2 (PGE2) and compare its dilator efficacy with the ß2-adrenoceptor agonist salbutamol in situ, using lung slices. Methods: Lung slices (150 µm) were prepared from male Balb/C mice. Changes in intrapulmonary airway lumen area were recorded and analysed by phase-contrast microscopy. Relaxation to PGE2 and salbutamol were assessed following various levels of pre-contraction with methacholine, serotonin or endothelin-1, as well as following overnight incubation with PGE2 or salbutamol. The mechanism of PGE2-mediated relaxation was explored using selective EP antagonists (EP1/2 AH6809; EP4 L-161982) and Ca2+-permeabilized slices, where airway responses are due to regulation of Ca2+-sensitivity alone. Results: PGE2 elicited EP1/2-mediated relaxation of intrapulmonary airways. PGE2 was more potent than salbutamol in opposing submaximal pre-contraction to all constrictors tested, and only PGE2 opposed maximal pre-contraction with endothelin-1. Relaxation to PGE2 was maintained when contraction to methacholine was mediated via increased Ca2+-sensitivity alone. PGE2 was less sensitive to homologous or heterologous desensitization of its receptors than salbutamol. Conclusion: The greater efficacy and potency of PGE2 compared to salbutamol in mouse intrapulmonary airways supports further investigation of the mechanisms underlying this improved dilator responsiveness for the treatment of severe asthma. © 2013.

DOI 10.1016/j.pupt.2013.11.005
Citations Scopus - 8
2014 Baker KE, Bonvini SJ, Donovan C, Foong RE, Han B, Jha A, et al., 'Novel drug targets for asthma and COPD: Lessons learned from invitro and invivo models', Pulmonary Pharmacology and Therapeutics, 29 181-198 (2014) [C1]

© 2014. Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent respiratory diseases characterized by airway inflammation, airway obstruction and airway hyper... [more]

© 2014. Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent respiratory diseases characterized by airway inflammation, airway obstruction and airway hyperresponsiveness. Whilst current therapies, such as ß-agonists and glucocorticoids, may be effective at reducing symptoms, they do not reduce disease progression. Thus, there is a need to identify new therapeutic targets. In this review, we summarize the potential of novel targets or tools, including anti-inflammatories, phosphodiesterase inhibitors, kinase inhibitors, transient receptor potential channels, vitamin D and protease inhibitors, for the treatment of asthma and COPD.

DOI 10.1016/j.pupt.2014.05.008
Citations Scopus - 21
2014 Donovan C, Simoons M, Esposito J, Ni Cheong J, FitzPatrick M, Bourke JE, 'Rosiglitazone is a superior bronchodilator compared to chloroquine and ß-adrenoceptor agonists in mouse lung slices', Respiratory Research, 15 (2014) [C1]

Background: Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characte... [more]

Background: Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where ß-adrenoceptor agonist efficacy was limited or impaired in mouse small airways within lung slices.Methods: Relaxation to RGZ and CQ was assessed following submaximal methacholine (MCh) pre-contraction, in slices treated overnight with either RGZ, CQ or albuterol (ALB) (to induce ß-adrenoceptor desensitization), and in slices treated with caffeine/ryanodine in which contraction is associated with increases in Ca2+ sensitivity in the absence of contractile agonist-induced Ca2+ oscillations. Furthermore, the effects of RGZ, CQ, ALB and isoproterenol (ISO) on the initiation and development of methacholine-induced contraction were also compared.Results: RGZ and CQ, but not ALB or ISO, elicited complete relaxation with increasing MCh pre-contraction and maintained their potency and efficacy following ß-adrenoceptor desensitization. RGZ, CQ and ALB maintained efficacy following overnight incubation with RGZ or CQ. Relaxation responses to all dilators were generally maintained but delayed after caffeine/ryanodine. Pre-treatment with RGZ, but not CQ, ALB or ISO, reduced MCh potency.Conclusions: This study demonstrates the superior effectiveness of RGZ in comparison to CQ and ß-adrenoceptor agonists as a dilator of mouse small airways. Further investigation of the mechanisms underlying the relatively greater efficacy of RGZ under these conditions are warranted and should be extended to include studies in human asthmatic airways. © 2014 Donovan et al.; licensee BioMed Central Ltd.

DOI 10.1186/1465-9921-15-29
Citations Scopus - 9
2013 Donovan C, Royce SG, Esposito J, Tran J, Ibrahim ZA, Tang MLK, et al., 'Differential Effects of Allergen Challenge on Large and Small Airway Reactivity in Mice', PLoS ONE, 8 (2013) [C1]

The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways dis... [more]

The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways disease to induce inflammation and remodelling and determine whether in vivo hyperresponsiveness to methacholine is consistent with in vitro reactivity of trachea and small airways. Balb/C mice were sensitised (days 0, 14) and challenged (3 times/week, 6 weeks) with ovalbumin. Airway reactivity was compared with saline-challenged controls in vivo assessing whole lung resistance, and in vitro measuring the force of tracheal contraction and the magnitude/rate of small airway narrowing within lung slices. Increased airway inflammation, epithelial remodelling and fibrosis were evident following allergen challenge. In vivo hyperresponsiveness to methacholine was maintained in isolated trachea. In contrast, methacholine induced slower narrowing, with reduced potency in small airways compared to controls. In vitro incubation with IL-1/TNFa did not alter reactivity. The hyporesponsiveness to methacholine in small airways within lung slices following chronic ovalbumin challenge was unexpected, given hyperresponsiveness to the same agonist both in vivo and in vitro in tracheal preparations. This finding may reflect the altered interactions of small airways with surrounding parenchymal tissue after allergen challenge to oppose airway narrowing and closure. © 2013 Donovan et al.

DOI 10.1371/journal.pone.0074101
Citations Scopus - 20Web of Science - 20
2012 Donovan C, Tan X, Bourke JE, 'PPAR ligands regulate noncontractile and contractile functions of airway smooth muscle: Implications for asthma therapy', PPAR Research, (2012) [C1]
DOI 10.1155/2012/809164
Citations Scopus - 12
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Conference (4 outputs)

Year Citation Altmetrics Link
2019 Budden K, Shukla S, Rehman SF, Sahu P, Donovan C, Bowerman KL, et al., 'The Role of the Gastrointestinal Microbiome in Lung Cancer Pathogenesis', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2019)
Co-authors Philip Hansbro
2017 Horvat JC, Alit M, Johnstone D, Essilfie A-T, Mayall J, Pinkerton JW, et al., 'Role Of Increased Iron Levels In The Pathogenesis Of Lung Disease', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Washington, DC (2017)
Co-authors Jay Horvat, Philip Hansbro, Liz Milward
2017 Tay HL, Hsu A, Nguyen T, Donovan C, Collison A, Mattes J, et al., 'Interleukin-36 gamma: Roles in lungs innate immunity, inflammation and allergy', CYTOKINE, Int Cytokine & Interferon Soc, Kanazawa, JAPAN (2017)
Co-authors Adam Collison, Alan Hsu, Gerard Kaiko, Ming Yang, Philip Hansbro, Paul Foster, Joerg Mattes, Hock Tay
2017 Ali MK, Kim R, Johnstone D, Essilfie A-T, Mayall J, Karim R, et al., 'ROLE OF INCREASED IRON LEVELS IN THE PATHOGENESIS OF LUNG DISEASE', RESPIROLOGY (2017)
Co-authors Jay Horvat, Philip Hansbro, Liz Milward
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Grants and Funding

Summary

Number of grants 5
Total funding $650,491

Click on a grant title below to expand the full details for that specific grant.


20182 grants / $416,411

Targeting remodelling in chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF)$396,411

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Doctor Chantal Donovan
Scheme Project Grant
Role Lead
Funding Start 2018
Funding Finish 2020
GNo G1700056
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Investigating the Genetics of the Development of Lung Cancer$20,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Miss Vrushali Chimankar, Associate Professor Jay Horvat, Doctor Chantal Donovan, Professor Philip Hansbro
Scheme Emlyn and Jennie Thomas Postgraduate Medical Research Scholarship
Role Investigator
Funding Start 2018
Funding Finish 2019
GNo G1800717
Type Of Funding C3120 - Aust Philanthropy
Category 3120
UON Y

20173 grants / $234,080

Targeting IL-33 in chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF)$213,007

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Doctor Chantal Donovan
Scheme Early Career Fellowships
Role Lead
Funding Start 2017
Funding Finish 2020
GNo G1600099
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

DVCRI Research Support for ECF$11,073

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Chantal Donovan
Scheme NHMRC ECF Support
Role Lead
Funding Start 2017
Funding Finish 2020
GNo G1700658
Type Of Funding Internal
Category INTE
UON Y

Flexivent FX base unit controller and software$10,000

Funding body: NSW Ministry of Health

Funding body NSW Ministry of Health
Project Team Associate Professor Jay Horvat, Doctor Chantal Donovan, Doctor Richard Kim, Doctor Shakti Shukla, Doctor Atiqur Rahman
Scheme Medical Research Support Program (MRSP)
Role Investigator
Funding Start 2017
Funding Finish 2017
GNo G1701220
Type Of Funding C2220 - Aust StateTerritoryLocal - Other
Category 2220
UON Y
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Research Supervision

Number of supervisions

Completed0
Current8

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2018 PhD Developing New Treatments in COPD PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2018 PhD Understand the Roles and Therapeutic Targeting of Macrophages in COPD PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2018 PhD Investigating Asthma-COPD Overlap Using Mouse Models PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2017 PhD Understanding the Molecular Basis of Chronic Respiratory Diseases through Multi-Omics Approaches PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2017 PhD Investigating the Development of New Treatments for Lung Cancer PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2017 PhD Elucidating and Targeting Genomic and Epigenetic Changes in the Development and Progression of Lung Cancer PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2016 PhD Investigating the Genetics and Epigenetics of the Development of Lung Cancer PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2016 PhD Mechanisms and Therapeutic Targeting of Immunometabolism in Lung Disease PhD (Immunology & Microbiol), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
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Dr Chantal Donovan

Position

Conjoint Fellow
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email chantal.donovan@newcastle.edu.au
Phone (02) 4042 0509
Link Twitter
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