Other areas of research

Researchers

Dr J. Margaret Hughes,
NHMRC Senior Researcher Pharmacy Practice

Dr Maria Sukkar,
Lecturer Pharmacy Practice

Dr Lisa Pont,
Lecturer Pharmacy Practice

Dr Betty Chaar,
Lecturer Pharmacy Practice

Research summary

Some research - ongoing within the Discipline - stands to one side of the main stream, for example

• Patient perspectives
• Tertiary teaching and learning
• Respiratory disease mechanisms
• Rural and aboriginal health, and
• Professional ethics.

Respiratory research mechanisms

Mast cell - airway smooth muscle interactions

We hypothesise that changes in intracellular signalling in airway smooth muscle cells from asthmatics cause their failure to release factor(s) that prevent mast cell chemotaxis and thus mast cell microlocalisation to the muscle in asthma. We hypothesised that altered intracellular signalling in airway smooth muscle (ASM) cells from asthmatics cause their failure to release factor(s) that reduce mast cell (MC) chemotaxis. Thus changes in ASM underlie mast cell localisation to the ASM and cellular abnormalities in asthma. We aim to identify signalling pathways involved in ASM production of factor(s) which inhibit MC chemotaxis to the ASM. we further aim to determine if differences in cell signalling underlie the failure of asthmatic ASM cells to release those inhibitory factor(s).
In asthma degranulating MC numbers on the ASM are increased and correlate with hyperresponsiveness and severity. Clearly MC-ASM interactions may contribute to the pathogenesis of asthma. To address the first aim, a list of candidate inhibitory factors will be prepared. Differences in protein release by ASM cells from 5-8 asthmatics and non-asthmatics will be explored by protein microarrays and any differences in candidate proteins identified and confirmed by real-time PCR and ELISA and their inhibitory activity tested in chemotaxis assays. To address the second aim, the signalling pathways involved in release of the inhibitory factor(s) by ASM cells from 5-8 non-asthmatic subjects will be determined using activity assays, immunoblotting, specific inhibitors, ELISAs and real-time PCR. Any changes in the signalling pathways leading to inhibitory factor production will then be detected in ASM cells from 5-8 asthmatic subjects. The identification of the endogenous inhibitory factor(s) will provide a key to understanding MC-ASM interactions in the pathogenesis of asthma and how to prevent them.

Airway smooth muscle innate immune receptor expression in inflammation of obstructive airway diseases

• TBA

Competitive Research Grants

• "Corticosteroids, mast cells, airway smooth muscle and remodelling in asthma"
  Hughes, Oliver, Armour
  Asthma Foundation NSW
  $50,000
  2009
• "Expression and function of the damage: Associated protein high-mobility Box-1 (HMGB1) in human airway smooth muscle"
  Sukkar
  Pharmacy Research Trust NSW
  $20,000
  2008 - 2009
• "High mobility group-box 1 and airway smooth muscle synthetic, proliferative and migratory function"
  Sukkar
  Asthma Foundation NSW
  $50,000
  2009
• "Airway smooth muscle control of mast cells in asthma"
  Hughes, Brightling, Ammit, Burgess, Armour
  NHMRC Project Grant # 457457
  $618,000
  2007 - 2009

Recent publications

1. Krimmer DI, Loseli M, Hughes JM, Oliver BGG, Moir L, Hunt NH, Black JL, Burgess JK (2009). CD40 and Ox40L are differentially regulated on asthmatic airway smooth muscle. Allergy 64: 1074-82.
2. Ammit AJ, Burgess JK, Hirst SJ, Hughes JM, Manminder Kaur, JYL, Zuyderduyn S (2008). The Effect of Asthma Therapeutics on Signalling and Transcriptional Regulation of Airway Smooth Muscle Function. In press, Pulmonary Pharmacol & Therapeutics doi:10.1016/j.pupt.2008.10.006.
3. Seidel P, Merfort I, Hughes JM, Oliver B, Tamm M, Roth M (2009). Dimethyl fumarate inhibit the NFkB pathway at multiple levels to limit airway smooth muscle cell cytokine secretion. In press, Amer J Physiol: Lung Cell Mol Physiol doi:10.1152/ajplung.90624.2008.
4. Parmentier P, Quante T, Ramsay EE, Schulz V, Schuster F, Henness S, Allen.C, Ge Q, Armour CL, Ammit AJ (submitted). Corticosteroids inhibit sphingosine 1-phosphate-induced IL-6 secretion from human airway smooth muscle. Am. J. Physiol.