Department of Pharmacology

Lung Disease Research Laboratory

LabPhoto

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 Publications


* Maxwell, M.J., Duan, M., Armes, J.E., Anderson, G.P., Tarlinton, D.M., and Hibbs, M.L., Genetic segregation of inflammatory lung disease and autoimmune disease severity in SHIP-1-/- mice. J Immunol. 186(12): p. 7164-75.

* Riise, G.C., Ericson, P., Bozinovski, S., Yoshihara, S., Anderson, G.P., and Linden, A., Increased net gelatinase but not serine protease activity in bronchiolitis obliterans syndrome. J Heart Lung Transplant. 29(7): p. 800-7.

* Lenzo, J.C., Turner, A.L., Cook, A.D., Vlahos, R., Anderson, G.P., Reynolds, E.C., and Hamilton, J.A., Control of macrophage lineage populations by CSF-1 receptor and GM-CSF in homeostasis and inflammation. Immunol Cell Biol.

* Tsantikos, E., Oracki, S.A., Quilici, C., Anderson, G.P., Tarlinton, D.M., and Hibbs, M.L., Autoimmune disease in Lyn-deficient mice is dependent on an inflammatory environment established by IL-6. J Immunol. 184(3): p. 1348-60.

* Ruwanpura, S.M., McLeod, L., Miller, A., Jones, J., Bozinovski, S., Vlahos, R., Ernst, M., Armes, J., Bardin, P.G., Anderson, G.P., and Jenkins, B.J., Interleukin-6 promotes Pulmonary Emphysema Associated with Apoptosis in Mice. Am J Respir Cell Mol Biol.

* Wong, Z.X., Jones, J.E., Anderson, G.P., and Gualano, R.C., Oseltamivir treatment of mice before or after mild influenza infection reduced cellular and cytokine inflammation in the lung. Influenza Other Respi Viruses.

* Duong, C., Seow, H.J., Bozinovski, S., Crack, P.J., Anderson, G.P., and Vlahos, R., Glutathione peroxidase-1 protects against cigarette smoke-induced lung inflammation in mice. Am J Physiol Lung Cell Mol Physiol. 299(3): p. L425-33.

* Hutchinson, A.F., Black, J., Thompson, M.A., Bozinovski, S., Brand, C.A., Smallwood, D.M., Irving, L.B., and Anderson, G.P., Identifying viral infections in vaccinated Chronic Obstructive Pulmonary Disease (COPD) patients using clinical features and inflammatory markers. Influenza Other Respi Viruses. 4(1): p. 33-9.

* Hutchinson, A.F., Thompson, M.A., Brand, C.A., Black, J., Anderson, G.P., and Irving, L.B., Community care assessment of exacerbations of chronic obstructive pulmonary disease. J Adv Nurs. 2010, 66(11): p. 2490-9.

* Tate, M.D., Deng, Y.M., Jones, J.E., Anderson, G.P., Brooks, A.G., and Reading, P.C., Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol, 2009. 183(11): p. 7441-50.

* Prause, O., Bossios, A., Silverpil, E., Ivanov, S., Bozinovski, S., Vlahos, R., Sjostrand, M., Anderson, G.P., and Linden, A., IL-17-producing T lymphocytes in lung tissue and in the bronchoalveolar space after exposure to endotoxin from Escherichia coli in vivo--effects of anti-inflammatory pharmacotherapy. Pulm Pharmacol Ther, 2009. 22(3): p. 199-207.

* Stampfli, M.R. and Anderson, G.P., How cigarette smoke skews immune responses to promote infection, lung disease and cancer. Nat Rev Immunol, 2009. 9(5): p. 377-84.

* Anderson, G.P., Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet, 2008. 372(9643): p. 1107-19.

* Chen, H., Hansen, M.J., Jones, J.E., Vlahos, R., Anderson, G.P., and Morris, M.J., Long-term cigarette smoke exposure increases uncoupling protein expression but reduces energy intake. Brain Res, 2008. 1228: p. 81-8.

* Glader, P., Eldh, B., Bozinovski, S., Andelid, K., Sjostrand, M., Malmhall, C., Anderson, G.P., Riise, G.C., Qvarfordt, I., and Linden, A., Impact of acute exposure to tobacco smoke on gelatinases in the bronchoalveolar space. Eur Respir J, 2008. 32(3): p. 644-50.

* Liu, K., Anderson, G.P., and Bozinovski, S., DNA vector augments inflammation in epithelial cells via EGFR-dependent regulation of TLR4 and TLR2. Am J Respir Cell Mol Biol, 2008. 39(3): p. 305-11.

* Bozinovski, S., Hutchinson, A., Thompson, M., Macgregor, L., Black, J., Giannakis, E., Karlsson, A.S., Silvestrini, R., Smallwood, D., Vlahos, R., Irving, L.B., and Anderson, G.P., Serum amyloid a is a biomarker of acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2008. 177(3): p. 269-78.

* Gualano, R.C., Hansen, M.J., Vlahos, R., Jones, J.E., Park-Jones, R.A., Deliyannis, G., Turner, S.J., Duca, K.A., and Anderson, G.P., Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice. Respir Res, 2008. 9: p. 53.

* Liu, K., Gualano, R.C., Hibbs, M.L., Anderson, G.P., and Bozinovski, S., Epidermal growth factor receptor signaling to Erk1/2 and STATs control the intensity of the epithelial inflammatory responses to rhinovirus infection. J Biol Chem, 2008. 283(15): p. 9977-85.

* Bozinovski, S., Vlahos, R., Zhang, Y., Lah, L.C., Seow, H.J., Mansell, A., and Anderson, G.P., Carbonylation Caused by Cigarette Smoke Extract is Associated with Defective Macrophage Immunity. Am J Respir Cell Mol Biol.

* Chen, H., Hansen, M.J., Jones, J.E., Vlahos, R., Bozinovski, S., Anderson, G.P., and Morris, M.J., Regulation of hypothalamic NPY by diet and smoking. Peptides, 2007. 28(2): p. 384-9.

* Chen, H., Hansen, M.J., Jones, J.E., Vlahos, R., Anderson, G.P., and Morris, M.J., Detrimental metabolic effects of combining long-term cigarette smoke exposure and high-fat diet in mice. Am J Physiol Endocrinol Metab, 2007. 293(6): p. E1564-71.

* Ivanov, S., Bozinovski, S., Bossios, A., Valadi, H., Vlahos, R., Malmhall, C., Sjostrand, M., Kolls, J.K., Anderson, G.P., and Linden, A., Functional relevance of the IL-23-IL-17 axis in lungs in vivo. Am J Respir Cell Mol Biol, 2007. 36(4): p. 442-51.

* Bozinovski, S., Vlahos, R., Hansen, M., Liu, K., and Anderson, G.P., Akt in the pathogenesis of COPD. Int J Chron Obstruct Pulmon Dis, 2006. 1(1): p. 31-8.

* O'Hehir, R.E., Sandrini, A., Anderson, G.P., and Rolland, J.M., Sublingual allergen immunotherapy: immunological mechanisms and prospects for refined vaccine preparation. Curr Med Chem, 2007. 14(21): p. 2235-44.

* Hutchinson, A.F., Ghimire, A.K., Thompson, M.A., Black, J.F., Brand, C.A., Lowe, A.J., Smallwood, D.M., Vlahos, R., Bozinovski, S., Brown, G.V., Anderson, G.P., and Irving, L.B., A community-based, time-matched, case-control study of respiratory viruses and exacerbations of COPD. Respir Med, 2007. 101(12): p. 2472-81.

* 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.

* 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.

* 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.

* 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.

* 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.

* 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.

* 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.

 

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