Arthritis & Inflammation
Arthritis and Inflammation Research Centre
In general the Hamilton group conducts research into inflammatory diseases within the Arthritis and Inflammation Research Centre and the Cooperative Research Centre for Chronic Inflammatory Diseases.
The major diseases studied are arthritis, atherosclerosis and cancer. The core biology involves that of the macrophage lineage. A variety of techniques and strategies are utilised including gene-based strategies (for example, micro-array technology) to understand disease causation, protein-based strategies (including proteomics, immunoprecipitation, cell transfection) to study the cellular signal transduction pathways associated with disease, and mouse models and clinical material to analyse disease in vivo.
Key components of the biology involve an analysis of how macrophage lineage cells are altered during inflammatory disease, how at a molecular level these cells survive, proliferate, differentiate or are activated, and how to down-regulate the cellular functions aberrant in disease. There is some emphasis on growth factor biology/biochemistry and on signal transduction pathways implicated strongly in human arthritis.
Current Projects
Title: GM-CSF and arthritis
Project Leader(s): Dr Andrew Cook
Staff/students: Mr Jarrad Pobjoy
For more information: adcook@unimelb.edu.au
Title: Plasminogen activators and arthritis
Project Leader(s): Dr Andrew Cook
Staff/students: Mr Jarrad Pobjoy
For more information: adcook@unimelb.edu.au
Title: The role of GM-CSF and CSF-1 in the control of macrophage lineage populations
Project Leader: Prof John Hamilton
Staff: Dr Jason Lenzo
For more information: jahami@unimelb.edu.au
Title: Macrophages in hypoxia
Project Leader: Prof John Hamilton
Staff: Amanda Turner
For more information: jahami@unimelb.edu.au
Title: Phenotypes of macrophage populations
Project Leader: Prof John Hamilton
Staff: Kaye Beckman; Dominic de Nardo
For more information: jahami@unimelb.edu.au
Title : Human macrophage and osteoclast development
Project Leader: Prof John Hamilton
Staff: Dominic de Nardo
For more information: jahami@unimelb.edu.au
Title: Stem cells, Inflammation and Wnt signalling
Project Leader(s): Dr Derek Lacey
Staff/students: Ms Nadene Tam
For more information: dlacey@unimelb.edu.au
Title: Arthritis, Macrophages and Wnt signalling
Project Leader(s): Dr Derek Lacey
For more information: dlacey@unimelb.edu.au
Title: Toll-like receptors and host defence against infection Project Leader: Dr Glen Scholz For more information: glenms@unimelb.edu.au
Title: SNAREs in the immune system
Project Leader: Dr Glen Scholz
For more information: glenms@unimelb.edu.au
Publications
- Cook AD, Braine EL, Campbell IK, Rich MJ, Hamilton JA. Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res. 2001;3:293-298.
- Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nature Reviews Immunol. 2008; 8:533-544.
- Hamilton JA, Tak PP. The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases. Arthritis & Rheum. 2009; 60: 1210-1221.
- Cook AD, Braine EL, Campbell IK, Hamilton JA. Differing roles for urokinase and tissue-type plasminogen activator in collagen-induced arthritis. Am J Pathol. 2002;160:917-926.
- Cook AD, Vlahos R, Massa CM, Braine EL, Lenzo JC, Turner AL, Way KJ, Hamilton JA. The effect of tissue type-plasminogen activator deletion and associated fibrin(ogen) deposition on macrophage localization in peritoneal inflammation. Thrombosis and Haemostasis 2006;95:659-667.
- Roiniotis J, Dinh H, Masendycz P, Turner A, Elsegood CL, Scholz GM, Hamilton JA. Hypoxia prolongs monocyte/macrophage survival and enhanced glycolysis is associated with their maturation under aerobic conditions. J. Immunol. 2009; 182:7974-7981.
- Fleetwood AJ, Lawrence T, Hamilton JA, Cook AD. GM-CSF- and M-CSF (CSF-1)-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities - implications for CSF blockade in inflammation, J. Immunol. 2007; 178:5245-5252.
- Fleetwood AJ, Hang D, Cook AD, Hertzog PJ, Hamilton JA. GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on Type I interferon signaling. J. Leuk. Biol. 2009;
- Way KJ, Dinh H, Keene MR, White KE, Clanchy FIL, Lusby P, Roiniotis J, Cook AD, Cassady AI, Curtis D, Hamilton JA. The generation and properties of human macrophage populations from hemopoietic stem cells. J. Leuk Biol. 2009; 85: 766-778.
- Lacey DC, Simmons PJ, Graves SE, Hamilton JA. Pro-Inflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation. Osteoarthritis and Cartilage 2009; 17: 735-742.
- De Nardo D, Masendycz P, Ho S, Cross M, Fleetwood AJ, Reynolds EC, Hamilton JA, Scholz GM. A central role for the Hsp90-Cdc37 molecular chaperone module in Interleukin-1 receptor-associated-kinase-dependent dependent signaling by toll-like receptors. J. Biol. Chem. 2005;280: 9813-9822.
- De Nardo D, Nguyen T, Hamilton JA, Scholz GM. Down-regulation of IRAK-4 is a component of LPS- and CpG DNA-induced tolerance in macrophages. Cellular Signalling, 2009;21(2):246-252.
- Nguyen T, De Nardo D, Masendycz P, Hamilton JA, Scholz GM. Regulation of IRAK-1 activation by its C-terminal domain. Cellular Signalling 2009; 21(5):719-726.
- Achuthan A, Masendycz P, Lopez JA, Nguyen T, James DE, Sweet MJ, Hamilton JA, Scholz GM. (2008) Regulation of endosomal SNARE protein syntaxin 7 by colony stimulating factor-1 in macrophages. 2008; Molecular and Cellular Biology 28:6149-59.