Molecular signaling pathways controlling gene expression during chronic disease progression

  • Project Lead

    Dr Adrian Achuthan
    T: +61 3 8344 3298
    E: aaa@unimelb.edu.au
    W: Personal web page

    Location: Dept of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia.

Project Details

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.

Researchers

Collaborators

  • Prof Stephen Nutt, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
  • Prof Stephen Turner, Monash University, VIC, Australia

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Outcomes

  1. 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.
  2. Hamilton JA and Achuthan A, Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol. 2013; 34(2):81-9.

Research Publications

  1. 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.
  2. 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.
  3. 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.
  4. Hamilton JA, Achuthan A. Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol. 2013 Feb;34(2):81-9.
  5. 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.
  6. 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.
  7. 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.
  8. 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.

Research Group

Hamilton Laboratory


Research Themes

Infection and Immunity


Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Medicine and Radiology