Molecular signaling pathways controlling gene expression during chronic disease progression
Inflammation is increasingly being seen to have a significant impact on many chronic diseases such as arthritis, cancer, Alzheimer’s disease, obesity/type II diabetes and heart diseases. The socio-economic burden of inflammatory diseases is enormous both in terms of direct health care costs and indirect non-health care costs.
Granulocyte macrophage-colony stimulating factor (GM-CSF) is a prosurvival factor for monocytes/macrophages, but also act as a proinflammatory cytokine. Thus, GM-CSF has been targetted in a number of clinical trials associated with inflammation. However, this may lead to undesirable side-effects, such as infections, given its role in prosurvival of immune cells. We are examining GM-CSF-mediated molecular signalling pathways controlling the expression of inflammatory genes critical for the progression of such inflammatory diseases.
- Dr Adrian Achuthan, Project Leader
- Prof John Hamilton
- A/Prof Andrew Cook
- Dr Andrew Fleetwood
- Ms Ashlee Frye, Research Assistant
- Prof Stephen Nutt, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
- Prof Stephen Turner, Monash University, VIC, Australia
- Lacey DC, Achuthan A, Fleetwood AJ et al, Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models. J Immunol. 2012; 188 (11): 5752-65.
- Hamilton JA and Achuthan A, Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol. 2013; 34(2):81-9.
- Huynh J, Scholz GM, Aw J, Kwa MQ, Achuthan A, Hamilton JA, Reynolds EC. IRF6 Regulates the Expression of IL-36γ by Human Oral Epithelial Cells in Response to Porphyromonas gingivalis.
J Immunol. 2016 Mar 1;196(5):2230-8.
- Fleetwood AJ, O'Brien-Simpson NM, Veith PD, Lam RS, Achuthan A, Cook AD, Singleton W, Lund IK, Reynolds EC, Hamilton JA. Porphyromonas gingivalis-derived RgpA-Kgp Complex Activates the Macrophage Urokinase Plasminogen Activator System: IMPLICATIONS FOR PERIODONTITIS. J Biol Chem. 2015 Jun 26;290(26):16031-42.
- Fleetwood AJ, Achuthan A, Schultz H, Nansen A, Almholt K, Usher P, Hamilton JA. Urokinase plasminogen activator is a central regulator of macrophage three-dimensional invasion, matrix degradation, and adhesion. J Immunol. 2014 Apr 15;192(8):3540-7.
- Hamilton JA, Achuthan A. Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol. 2013 Feb;34(2):81-9.
- Lacey DC, Achuthan A, Fleetwood AJ, Dinh H, Roiniotis J, Scholz GM, Chang MW, Beckman SK, Cook AD, Hamilton JA. Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models. J Immunol. 2012 Jun 1;188(11):5752-65.
- Achuthan A, Masendycz P, Lopez JA, Nguyen T, James DE, Sweet MJ, Hamilton JA, Scholz GM. Regulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages. Mol Cell Biol. 2008 Oct;28(20):6149-59.
- Achuthan A, Elsegood C, Masendycz P, Hamilton JA, Scholz GM. CpG DNA enhances macrophage cell spreading by promoting the Src-family kinase-mediated phosphorylation of paxillin. Cell Signal. 2006 Dec;18(12):2252-61.
- Manes GA, Masendycz P, Nguyen T, Achuthan A, Dinh H, Hamilton JA, Scholz GM. A potential role for the Src-like adapter protein SLAP-2 in signaling by the colony stimulating factor-1 receptor. FEBS J. 2006 Apr;273(8):1791-804.