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Dr. Charles Hardy BSc, PhD

Current Position:
Senior Research Officer, Allergy Research Laboratory

Phone:
+ 61 3 9903 0697

Facsimile:
+ 61 3 9903 0038

Email:
charles.hardy@med.monash.edu.au

Office and Laboratory:
Department of Immunology
Level 2, Monash University Building, AMREP
Commercial Road
Melbourne 3004

Research Background:
Dr. Charles Hardy completed his PhD at the University of Melbourne in 1996. Since then he has worked with Drs Roland Scollay and Dale Godfrey at the Centenary Institute of Cancer Medicine and Cell Biology, and with Professor Peter Doherty and Dr. Marcia Blackman at St Jude Children’s Research Hospital, Memphis USA.  In 2000 he relocated to Australia to join ProfessorRobyn O’Hehir and Associare Professor Jennifer Rolland as Senior Research Officer in the CRC for Asthma. He supervises a small research team including an Honours and PhD student, studying immunomodulation in mouse models of allergic airway inflammation within the larger allergy group.

He has established and maintains productive collaborations investigating novel vaccine technologies in experimental asthma with Associate Professor Magdalena Plebanski (Austin Research Institute), and the role of activin (a member of the TGF-b superfamily) in pulmonary inflammation and airway remodelling with Dr. David Phillips and Professor David de Kretser (Monash Institute of Reproduction and Development). This latter project is ongoing, and was recently awarded a Monash Small Grant.  He has published consistently in top-ranked specialty journals in the fields of virology and allergy over the last 5 years, including J Immunol, Eur J Immunol,  J Virol and Am J Respir and Crit Care Med.

Dr. Hardy has extensive experience studying immunopathological processes in mouse models of human disease, and is familiar with techniques ranging from production of transgenic animals through to molecular biology and cellular immunology.  He is a member of the Australian Society for Immunology, and a regular invited reviewer for The Journal of Allergy and Clinical Immunology, Clinical and Experimental Allergy, and International Archives of Allergy and Immunology.  From 2001–2004 he co-ordinated the Department of Immunology and Macfarlane Burnet Institute joint seminar series, and in 2005 co-ordinated the Department of Immunology Annual Symposium.  He has presented his research at numerous national and international conferences, and was recently invited to write an editorial on recombinant allergen immunotherapy for the Journal Clinical and Experimental Allergy.

Current Research Focus:

Work funded by the Asthma CRC:
We have developed mouse models of allergic airway inflammation to the occupational allergen latex, and to the seasonal aeroalleren couch grass (Bermuda).  We have identified immunodominant T cell epitopes (protein fragments which potently stimulate immune responses) within key latex and couch grass allergens, Hev b 6 and Cyn d 1, respectively.  Using these immunodominant epitopes and modified allergens with reduced allergic potential (hypoallergenic allergens) we aim to identify mechanisms which downregulate experimental allergic asthma symptoms. 

Work funded by NHMRC Program Grant (Professor Robyn O'Hehir, Associate Professor Gary Anderson, Professor John Hamilton, Associate Professor Jennifer Rolland):
We are exploring the role of activin A, a member of the transforming growth factor-beta superfamily, in allergic airway inflammation and airway remodelling.  Growing evidence supports a role for activin A in human and experimental asthma.  We have recently shown that expression/compartmentalization of activin A and its natural inhibitor, follistatin, is markedly altered in a mouse model of allergic airway inflammation.  Our findings suggest that activin A and follistatin are pre-stored in normal airway epithelium, and released into the surrounding tissue during airway inflammation, both in mice receiving acute (short term) and chronic (long term) allergen challenges.  Taken together with data from other groups our findings support the idea that activin A is involved in airway remodelling, a key feature of chronic asthma in humans.  We are currently exploring whether airway remodelling can be inhibited by follistatin and other molecules which interfere with activin receptor signalling. 

Collaborative work with Associate Professor Magdalena Plebanski:
Airborne particulate matter can be graded into 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 these particles exert their effect on lung dendritic cells (a cell population which critically regulates immune responses).

Selected Publications:

  1. 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.
  2. Hardy CL, Rolland JM, O’Hehir RE. Blocking antibodies in allergen immunotherapy: the Yin and Yang.  Clin Exp Allergy, 2004; 34: 510–512.
  3. 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.
  4. 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.
  5. Purton JF, Zhan Y, Liddicoat DR, Hardy CL, Lew AM, Cole TJ, Godfrey DI. Glucocorticoid receptor deficient thymic and peripheral T cells develop normally in adult mice. Eur J Immunol. 2002; 32(12): 3546-55.
  6. Ng DP, Hardy CL, Burns WC, Muggli EE, Kerr N, McCausland J, Alcorn D, Adams TE, Zajac JD, Larkins RG, Dunlop ME.  Prevention of diabetes-induced albuminuria in transgenic rats overexpressing human aldose reductase. Endocrine. 2002; 18(1):47-56.
  7. Hardy CL, Flano E, Cardin RD, Kim IJ, Nguyen P, King S, Woodland DL, Blackman MA.  Factors controlling levels of CD8+ T-cell lymphocytosis associated with murine gammaherpesvirus infection. Viral Immunol. 2001; 14(4):391-402.
  8. Hardy CL, Godfrey DI, Scollay R.  The effect of antigen stimulation on the migration of mature T cells from the peripheral lymphoid tissues to the thymus. Dev Immunol. 2001;8(2):123-31.
  9. Hardy CL, Lu L, Nguyen P, Woodland DL, Williams RW, Blackman MA.  Identification of quantitative trait loci controlling activation of TRBV4 CD8+ T cells during murine gammaherpesvirus-induced infectious mononucleosis. Immunogenetics. 2001; 53(5):395-400.
  10. Grech AP, Riminton DS, Gabor MJ, Hardy CL, Sedgwick JD, Godfrey DI.  Increased thymic B cells but maintenance of thymic structure, T cell differentiation and negative selection in lymphotoxin-alpha and TNF gene-targeted mice. Dev Immunol. 2000; 8(1):61-74.