Current Position:
Senior Research Officer, Allergy Research Laboratory
Phone: + 61 3 9903 0697
Facsimile: + 61 3 9903 0038
Email: charles.hardy@monash.edu
Office and Laboratory:
Department of Immunology
Level 2, Monash University Building, AMREP
Commercial Road
Melbourne 3004
Background, skills and publications
Dr. Hardy completed his PhD at the University of Melbourne in 1996, and undertook post-doctoral studies with Prof. Dale Godfrey (Centenary Institute of Cancer Medicine and Cell Biology) and Dr. Marcia Blackman in the Department of Immunology chaired by Nobel Laureate Peter Doherty (St Jude Children’s Research Hospital). He is currently a Senior Research Fellow in the laboratories of Profs Robyn O’Hehir and Jennifer Rolland in the Department of Immunology, Monash University. He supervises a research team of PhD students and RA on projects investigating pulmonary immunomodulation, fibrosis and the effect of diet and gut microbiota on asthma. He has extensive experience developing and characterising mouse models of lung immunopathologies, including lung virus infection models, models of acute and chronic asthma, and cystic fibrosis. He has 21 publications, including 12 as first author. These include publications in the field of lung viral immunology, and recent publications on the role of activin A in pulmonary immune function and fibrosis in allergic asthma, as well as the role of inert nanoparticles in the inhibition of experimental asthma. He has several papers currently under review or being prepared for publication including work investigating the fibrotic role of activin A in asthmatic airway remodelling (fibrosis) and cystic fibrosis, and the effects of ultrafine nanoparticles on pulmonary immune function.
Grant and patents
Dr. Hardy’s research on the role of activin A in asthma has been recognised by the awarding of a Monash University strategic grant, and two recent grants by the philanthropic CASS Foundation ‘Follistatin therapy for cystic fibrosis and other lung inflammatory diseases’ (2010 & 2011). He was CI on an NHMRC Project Grant (2008–2010) ‘Inhibition of allergic airway inflammation by nanoparticles’. This project provided highly novel insights into the effects of nanoparticles on lung immunobiology, with several manuscripts currently under review. He is CI on a recently awarded NHMRC Project Grant (2011–2013) ‘Mechanisms of nanoparticle-mediated inhibition of asthma’ which is an extension of this research. He is a co-inventor on a related Patent ‘A method for prophylaxis and agents for use therein’. Most recently he was awarded an NHMRC Project Grant (2012–2014) to investigate the effect of diet and gut microbiota on respiratory immunological tolerance in asthma.
Scientific community
Dr Hardy contributes to the scientific community as a peer reviewer for top-ranked Immunology and Allergy scientific journals. He is a grant reviewer for the Asthma Foundation of Western Australia, National Health & Medical Research Council, the Child Health Research Foundation, Western Australia, and the Asthma Foundation of Victoria. He served as scientific member on the Alfred Medical Research and Education Precinct (AMREP) Animal Ethics Committee from 2008–2010. He is currently on the organising committee for the International Day of Immunology (Victoria), where he co-developed a competition for Victorian primary school children aimed at increasing awareness of the vital role that the immune system plays in maintaining good health. This competition is being run for the first time in 2011.
Current Research Focus:
Regulation of pulmonary immunity by ultrafine nanoparticles.
In collaboration with Professor Magdalena Plebanski (CRC for Asthma and Airways and NHMRC Project Grants).
Airborne particulate matter can be classified as coarse, fine and ultrafine particle sizes. There is a large body of evidence suggesting that fine and ultrafine particulate matter is associated with asthma exacerbations. We have identified a novel pathway via which inert ultrafine particles surprisingly inhibit allergic airway inflammation in mice. We are currently exploring the mechanism of action and have evidence suggesting that polystyrene nanoparticles leave a distinct ‘immunological imprint’ in the lung which modifies the immune-regulatory function of lung dendritic cells and regulatory T cell (Treg).
The role of activin A in asthma – effect of inhibition with follistatin
(NHMRC Program Grants and CRC for Asthma and Airways).
Work by us and others has shown that activin A, a member of the TGF-b superfamily, is involved in regulating inflammation in the lung. We previously showed that blocking activin A with its natural antagonist follistatin, a high-affinity binding protein, attenuates allergic airway inflammation. More recently we showed that blocking activin A with follistatin during chronic allergen challenge inhibits the tissue structural changes, termed airway remodelling, in a mouse model of chronic asthma.
The role of activin A in cystic fibrosis – effect of inhibition with follistatin.
In collaboration with Professor Fabienne Mackay and Professor David de Kretser, Monash Institute of Medical Research (CASS Foundation Research Grants).
Cystic fibrosis is one of the most common inherited genetic disorders, and results in severely decreased quality of life, and shortened lifespan. The main life-threatening complication is loss of lung function, the only treatment currently being lung transplantation. Mice which have an introduced mutation in the lung epithelial sodium chloride channel (Scnn1b transgenic mice) replicate several key features of the human disease including increased mucus production in the lung airways and greatly decreased lifespan. We are currently investigating whether blocking activin A via follistatin instillation into the lungs of newborn mice affects cystic fibrosis lung pathology and life-span.
The effect of diet and gut microbiota on respiratory inhalational tolerance – the link with asthma.
In collaboration with Professor Fabienne Mackay and Professor Charles Mackay, Monash University and Clinton Bruce, Baker IDI (NHMRC Project Grant)
There is now strong evidence that the bacteria which inhabit our gut (gut microbiota) directly regulate the immune system in a variety of ways. Our gut microbial populations are shaped by the foods that we eat. This project will investigate the observed correlation between obesity and asthma by exploring the hypothesis that obesity-associated alterations in the gut microbiota impair the development of inhalational respiratory tolerance, a key mechanism thought to prevent the development of allergic asthma.
Selected Publications
For a full list of publications see Dr Charles Hardy's bibliography
- Hardy CL, LeMasurier JS, Belz GT, Scalzo-Inguanti K, Yao J, Xiang SD, Kanellakis P, Bobik A, Strickland DH, Rolland JM, O’Hehir RE and Plebanski M. Inert 50 nm polystyrene nanoparticles that modify pulmonary dendritic cell function and inhibit allergic airway inflammation. J. Immunol. 2011, in press.
- de Kretser DM, O'Hehir RE, Hardy CL, Hedger MP. The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair. Mol Cell Endocrinol 2011; In press.
- Hardy CL, Nguyen HA, Mohamud R, Yao J, Plebanski M, Rolland JM, O’Hehir RE. Follistatin inhibits airway remodelling in a murine model of chronic asthma. Collegium Internationale Allergologicum 28th Symposium. Accepted.
- Hardy CL, Lemasurier JS, Olsson F, Dang T, Yao J, Yang M, Plebanski M, Phillips DJ, Mollard R, Rolland JM, O'Hehir RE. IL-13 regulates secretion of the TGF- superfamily cytokine activin A in allergic airway inflammation. Am. J. Respir. Cell Mol Biol. 2010 42: 667–675.
- Xiang SD, Scalzo-Inguanti K, Minigo G, Park A, Hardy CL, Plebanski M. Promising particle-based vaccines in cancer therapy. Expert Rev. Vaccines 2008; 7(7) 1103–1119. Citations 4.
- Hardy CL, O’Connor AE, Yao J, Sebire K, de Kretser DM, Rolland JM, Anderson, GP, Phillips DJ, and O’Hehir RE. Follistatin is a candidate endogenous negative regulator of activin A in experimental allergic asthma. Clin. Exp. Allergy, 2006 36: 941–950. Citations 11.
- Hardy CL, Rolland JM, O’Hehir RE. Blocking antibodies in allergen immunotherapy: the Yin and Yang. Clin. Exp. Allergy, 2004; 34: 510–512. Citations 8.
- Flaño E, Hardy CL, Kim IJ, Frankling C, Coppola MA, Nguyen P, Woodland DL, Blackman MA. T cell reactivity during infectious mononucleosis and persistent gammaherpesvirus infection in mice. J. Immunol. 2004; 172(5): 3078–3085. Citations 6.
- Hardy CL, Kenins L, Drew AC, Rolland JM, O’Hehir RE. Characterisation of a mouse model of allergy to a major occupational latex glove allergen Hev b 5. Am J Respir Crit Care Med 2003; 167: 1393–1399.
