Cell Signalling and Lung Disease
- Dr Steve Bozinovski
Steven Bozinovski, PhD
CR Roper Senior Research Fellow
Department of Pharmacology
University of Melbourne
Email: bozis@unimelb.edu.au
Phone: +61 3 8344 4221
Dr Steven Bozinovski's research activities focus on the molecular mechanisms that drive persistent inflammation observed in chronic lung disease. Defects in the innate immune cells such as macrophages and neutrophils can contribute to chronic damage in lung diseases including COPD and asthma, which drive pathological airway changes in a manner that is resistant to standard therapies including Glucocorticosteroids (GCS). A major pathway responsible for recognition and response to pathogens and damaged tissue are the TLR receptors. Dr Bozinovski's group is particularly interested in understanding how TLRs are regulated in the airways and how these processes are altered in chronic lung disease. Another research stream is exploring how the setting of chronic inflammation can influence susceptibility and progression of lung cancer.
In collaboration with the Respiratory Department at Royal Melbourne Hospital, proteomic and molecular approaches are used to screen for predictive COPD exacerbation biomarkers in large clinical cohorts. This work has lead to the discovery of SAA as a marker of exacerbation severity that may help in identifying patients at greatest risk of hospitalisation due to respiratory failure. Since SAA exerts various biological activities we are now exploring its role in driving GCS resistant airway inflammation and the potential of therapeutically targeting SAA in chronic lung disease.
.....................................................
Key Publications
Bozinovski S, Vlahos R, Zhang Y, Lah L, Seow H, Mansell A and Anderson GP. Carbonylation caused by cigarette smoke extract is associated with defective macrophage immunity. (Am J Resp Cell Mol Biol Oct 8 Epub ahead of print).
Bozinovski S, Uddin M, Vlahos R, Thompson M, Merritt A-S, Wark PAB, Hutchinson A, Irving LB, Levy BD and Anderson GP. Serum Amyloid A and Lipoxin A4 Interact with ALX/FPR2 Receptors To Modulate Airway Mucosal Inflammation in COPD (Science TM in review September 2010).
Bozinovski S, Hutchinson A, Thompson M, Macgregor L, Black J, Giannakis E, Karlsson AS, Silvestrini R, Smallwood D, Vlahos R, Irving LB, Anderson GP. Serum Amyloid A is a Biomarker of Acute Exacerbations of COPD. Am Jour Resp Critical Care Med. 2008 Sep; 32(3):644-50
Liu K, Gualano RC, Hibbs M, Anderson GP, Bozinovski S . EGFR signalling to Erk1/2 and STATs control the intensity of epithelial inflammatory responses to rhinovirus infection. Jour Biol Chem. 2008 Apr 11; 283 (15):9977-85.
Liu K, Anderson GP, Bozinovski S . DNA vector augments inflammation in epithelial cells via EGFR dependent regulation of TLR4 and TLR2. Am Jour Resp Cell Mol Biol. 2008 Sep;39(3):305-11.
Ivanov S, Bozinovski S, Bossios A, Valadi H, Vlahos R, Malmhall C, Sjostrand M, Kolls JK, Anderson GP, Linden A. Functional Relevance of the IL-23-IL-17 Axis in Lungs in vivo. Am Jour Resp Cell Mol Biol. 2007 Apr; 36 (4):442-51.
Vlahos, R., Bozinovski S ., Jones, J.E., Lilja, A., Hansen, M.J., Gualano, R.C., Irving, L., & Anderson, G.P. Differential protease, innate immunity and NFkB induction profiles during lung inflammation induced by sub-chronic smoke exposure in Balb/c mice. Am Jour of Phys- Lung Cell Molecular Physiology 2006 May; 290 (5):L931-45
Bozinovski S, Cross M, Vlahos R, Jones J, Hsuu K, Tessier P, Reynolds E, Hume D, Hamilton J, Geczy C & Anderson G. S100A8 chemotactic protein is abundantly increased, but only a minor contributor to LPS-induced, steroid resistant neutrophilic lung inflammation in vivo. Jour Proteome Research 2005 Feb14; 4(1):136-145.
Bozinovski S, Jones J, Beavitt SJ, Cook AD, Hamilton JA, Anderson GP. Innate immune responses to lipopolysaccharide in mouse lung are suppressed and reversed by neutralization of GM-CSF via repression of TLR-4. Am Jour Phys- Lung Cell Molecular Physiology 2004 Apr; 286 (4):L877-85.
Anderson GP & Bozinovski S. Acquired somatic mutations in the molecular pathogenesis of COPD. Trends Pharmacological Sciences 2003 24(2): 71-6.
Bozinovski S, Jones JE, Vlahos R, Hamilton JA, Anderson GP. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) regulates lung innate immunity to lipopolysaccharide through Akt/Erk activation of NFkappa B and AP-1 in vivo. Jour Biol Chem 2002 (45): 42808-14.
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, Dunn AR. Constitutive activation of the SRC family kinase Hck results in spontaneous pulmonary inflammation and an enhanced innate immune response. Jour Exp Med; 2002 196(5): 589-604.
Mitchell B.H, Griffiths J, Tiganis T, Bozinovski S, Kemp B and Pearson R.B. Akt directly phosphorylates and activates eNOS in endothelial cells. Current Biology 1999 (15): 845-8.