Department of Pharmacology

Lung Disease Research Laboratory

Research

Research in our laboratory is aimed at understanding the molecular processes that underly induction, progression, severity and exacerbation of chronic inflammatory lung conditions, especially asthma and chronic obstructive lung disease (COPD).

Our group is a core laboratory of the Cooperative Research Centre for Chronic Inflammatory Diseases (CRC-CID) providing lung biology expertise. The CRC-CID (website: macrophages.com) is a national organisation of around 100 scientists focussed on identifying novel therapeutic targets for chronic inflammatory disease of the lungs and joints, in partnership with AstraZeneca Pharmaceuticals.

Our current research is centred on the macrophage biology of lung inflammation, innate immunity signalling in vivo, and murine models of asthma and COPD including viral exacerbations of these conditions. Our laboratory has a special interest in defining disease pathways thorough the in vivo application of genomic and proteomic profiling methods.
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Key References

* Prause O, Bozinovski S, Anderson GP, Linden A. Increased matrix metalloproteinase-9 concentration and activity after stimulation with interleukin-17 in mouse airways. Thorax. 2004 59:313-7.
* Bozinovski S, Jones J, Beavitt SJ, Cook AD, Hamilton JA, Anderson GP. Innate immune responses to LPS in mouse lung are suppressed and reversed by neutralization of GM-CSF via repression of TLR-4. Am J Physiol Lung Cell Mol Physiol. 2004;286(4):L877-85. Epub 2003 Nov 14.
* Anderson GP and Bozinovski S. Acquired somatic mutations in the molecular pathogenesis of COPD. Trends Pharmacol Sci. 2003;24:71-76.
* Shinagawa K, Trifilieff A and Anderson GP. Involvement of CCR3-reactive chemokines in eosinophil survival. Int Arch Allergy Immunol. 2003;130:150-157.
* Ernst M, Inglese M, Scholz GM, Harder KW, Clay FJ, Bozinovski S, Waring P, Darwiche R, Kay T, Sly P, Collins R, Turner D, Hibbs ML, Anderson GP and Dunn AR. Constitutive activation of the SRC family kinase Hck results in spontaneous pulmonary inflammation and an enhanced innate immune response. J Exp Med. 2002;196(5):589-604.
* Bozinovski S, Jones JJ, Vlahos R, Hamilton JA and Anderson GP. GM-CSF regulates lung innate immunity to LPS through Akt/Erk activation of NFkB and AP-1 in vivo. J Biol Chem. 2002;277:42808-42814.
* Anderson GP. Therapeutic prospects for early asthma. Med J Aust. 2002;177(6 Suppl):S66-69.
* Anderson GP. The immunobiology of early asthma. Med J Aust. 2002;177(6 Suppl):S47-49.
* Mah R, Gerspacher M, von Sprecher A, Stutz S, Tschinke V, Anderson GP, Bertrand C, Subramanian N and Ball HA. Biphenyl derivatives as novel dual NK(1)/NK(2)-receptor antagonists. Bioorg Med Chem Lett. 2002;12(16):2065-2068.
* Gerspacher M, La Vecchia L, Mah R, von Sprecher A, Anderson GP, Subramanian N, Hauser K, Bammerlin H, Kimmel S, Pawelzik V, Ryffel K and Ball HA. Dual neurokinin NK(1)/NK(2) antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N’-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N’-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides. Bioorg Med Chem Lett. 2001;11(23):3081-3084.
* Roth M, Johnson PRA, Rudiger JJ, King GG, Ge Q, Burgess JK, Anderson GP, Black JL, and Tam M. Interactions between glucocortiosteroids and beta-agonist on bronchial airway smooth muscle through synchronized cellular signaling, Lancet, 2002;360:1293-1299.
* Bozinovski S, Cristiano BE, Marmy-Conus N, Pearson RB. The Synthetic Peptide RPRAATF Allows Specific Assay of Akt Activity in Cell Lysates. Anal Biochem. 2002;305(1):32-39.
* Ivanov, S.N., Vlahos, R., Bozinovski, S., Bossios, A., Malmhall, C., Sjostrand, M., Kolls, J.K., Anderson, G.P. & Linden, A. (2006) Functional relevance of the IL-23 – IL-17 axis in intact lungs in vivo. American Journal of Respiratory Cell and Molecular Biology , Dec 1; [Epub ahead of print].
* Chen, H., Hansen, M.J., Jones, J.E., Vlahos, R., Bozinovski, S., Anderson, G.P. & Morris, M.J. (2006) Cigarette smoke exposure reprograms the hypothalamic neuropeptide Y appetite axis to promote anorexic associated weight loss. American Journal of Respiratory and Critical Care Medicine, 173, 1248-1254.
* Vlahos, R., Bozinovski, S., Hamilton, J.A. & Anderson, G.P. (2006) Therapeutic potential of treating COPD by neutralising GM-CSF. Pharmacology and Therapeutics, 112 (1), 106-115.
* Bozinovski, S., Vlahos, R., Hansen, M.J., Liu, K. & Anderson, G.P. (2006) Akt in the pathogenesis of COPD. International Journal of COPD, 1, 31-38.
* Vlahos, R., Bozinovski, S., Jones, J.E., Powell, J., Gras, J., Lilja, A., Hansen, M.J., Gualano, R.C., Irving, L, & Anderson, G.P. (2006) Differential protease, innate immunity and NFkB induction profiles during lung inflammation induced by sub-chronic cigarette smoke exposure in mice. American Journal of Physiology – Lung Cellular and Molecular Physiology, 290(5), L931-L945.
* Hansen, M.J., Gualano, R.C., Bozinovski, S., Vlahos, R. & Anderson, G.P. (2006) Therapeutic prospects to treat skeletal muscle wasting in COPD. Pharmacology and Therapeutics, 109 (1-2), 162-172.
* Gualano, R.C., Vlahos, R. & Anderson, G.P. (2006) What is the contribution of respiratory viruses and lung proteases to airway remodelling in asthma and chronic obstructive pulmonary disease? Pulmonary Pharmacology and Therapeutics, 19 (1), 18-23.
* Vlahos, R., Bozinovski, S., Gualano, R.C., Ernst, M. & Anderson, G.P. (2006) Modelling COPD in mice. Pulmonary Pharmacology and Therapeutics, 19 (1), 12-17.
* Bozinovski, S., Cross, L., Vlahos, R., Tessier, P., Geczy, C., Hume, D., Hamilton, J.A. & Anderson, GP. (2005) S100A8 chemotactic protein is abundantly increased, but only a minor contributor to LPS-induced, steroid resistant neutrophilic lung inflammation in vivo. Journal of Proteome Research, 4(1), 136-45.
* Chen, H., Vlahos, R., Bozinovski, J., Jones, J.E., Anderson, G.P. & Morris, M.J. (2005) Effect of Short-Term Cigarette Smoke Exposure on Body Weight, Appetite and Brain Neuropeptide Y in Mice. Neuropsychopharmacology, 30(4), 713-719.

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