The Walter and Eliza Hall Institute of Medical Research

Professor Ian Wicks

Details

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Division: Inflammation

Research Overview

This laboratory focuses on the intersection between inflammation and autoimmunity, as exemplified by diseases such as rheumatoid arthritis (RA). RA is a common human disease which targets synovial joints, causing chronic joint pain, stiffness, progressive joint deformity and disability. Chronic systemic inflammation also causes accelerated atherosclerosis and cardiovascular disease is the main cause of the premature mortality that occurs in RA. The autoantigens driving RA remain obscure, but prominent activation of innate as well as adaptive immune mechanisms is characteristic of RA. In particular, there is sustained over- production of pro-inflammatory cytokines, such as TNF. Therapeutic antagonism of TNF is now used in the clinic for RA and associated diseases. However, not all patients respond to anti-TNF treatment and this is likely to be the first wave of a new era in anti-cytokine therapeutics. In addition to understanding fundamental pathological responses during inflammation, we aim to identify potential biomarkers and evaluate new therapeutic targets for diseases such as RA. We also believe that what we learn from studying RA is highly likely to be relevant to many other inflammatory diseases.

Our research has relied on well-characterised experimental models to uncover roles in inflammation for cytokines that were originally discovered at the Walter and Eliza Hall Institute in the context of haematopoeisis – particularly G-CSF and GM-CSF. We have been exploring how these cytokines amplify autoimmune responses to cause disease, especially via the contributions of neutrophils and macrophages. We have also recently become interested in how cell death pathways help resolve established joint inflammation. Our work has generated biotechnology partnerships to develop antibody-based therapeutics targeting G-CSF and GM-CSF.

Research Interests

• How do endogenous G-CSF, GM-CSF and IL-17 amplify autoimmunity during inflammatory arthritis and other inflammatory diseases?
• Understanding the role of SOCS-3 in different cell types during inflammatory arthritis
• How does the p50 subunit of NF-kB regulate inflammatory arthritis?
• How do interactions between cells of the inflammatory synovial microenvironment and T cells influence subsequent T cell differentiation?
• The role of AIRE and central tolerance in collagen induced arthritis

Wicks Laboratory supporters

Selected Publications

1. Campbell IK, Hamilton J, Wicks IP. Collagen-induced arthritis in C57BL/6 mice (H-2b): new insights into an important disease model of rheumatoid arthritis. Eur J Immunol. 2000 Jun;30(6):1568-75 PMID: 10898492 [PubMed - indexed for MEDLINE]
2. Campbell IK, Gerondakis S, O'Donnell K, Wicks IP. Distinct roles for the NF-kappaB1 (p50) and c-Rel transcription factors in inflammatory arthritis. J Clin Invest. 2000 Jun;105(12):1799-806. PMID: 10862795 [PubMed - indexed for MEDLINE]
3. Campbell IK, O'Donnell K, Lawlor KE, Wicks IP. Severe inflammatory arthritis and lymphadenopathy in the absence of TNF. J Clin Invest. 2001 Jun;107(12):1519-27. PMID: 11413159 [PubMed - indexed for MEDLINE]
4. Egan PJ, Lawlor KE, Alexander WS, Wicks IP. Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation. J Clin Invest. 2003 Mar;111(6):915-24. PMID: 12639998 [PubMed - indexed for MEDLINE]
5. Lawlor KE, Campbell IK, Metcalf D, O'Donnell K, van Nieuwenhuijze A, Roberts AW, Wicks IP. Critical role for granulocyte colony-stimulating factor in inflammatory arthritis. Proc Natl Acad Sci USA. 2004 Aug 3;101(31):11398-403. Epub 2004 Jul 22. PMID: 15272075 [PubMed - indexed for MEDLINE]
6. Wong PK, Quinn JM, Sims NA, van Nieuwenhuijze A, Campbell IK, Wicks IP. Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum. 2006 Jan;54(1):158-68 PMID: 16385511 [PubMed - indexed for MEDLINE]
7. Wong PK, Egan PJ, Croker BA, O'Donnell K, Sims NA, Drake S, Kiu H, McManus EJ, Alexander WS, Roberts AW, Wicks IP. SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J Clin Invest. 2006 Jun;116(6):1571-81 PMID: 16710471 [PubMed - indexed for MEDLINE]
8. Eyles JL, Hickey MJ, Norman MU, Croker BA, Roberts AW, Drake SF, James WG, Metcalf D, Campbell IK, Wicks IP. A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis. Blood. 2008 Dec 15;112(13):5193-201. Epub 2008 Sep 29. PMID: 18824600 [PubMed - indexed for MEDLINE]
9. Egan PJ, van Nieuwenhuijze A, Campbell IK, Wicks IP. Promotion of the local differentiation of murine Th17 cells by synovial macrophages during acute inflammatory arthritis. Arthritis Rheum. 2008 Dec;58(12):3720-9. PMID: 19035489 [PubMed - indexed for MEDLINE]
10. Cornish AL, Campbell IK, McKenzie BS, Chatfield S, Wicks IP. G-CSF and GM-CSF as therapeutic targets in rheumatoid arthritis. Nat Rev Rheumatol. 2009 Oct;5(10):554-9. PMID: 19798030 [PubMed - in process]

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Current Laboratory Members

Faculty Member: Ian Wicks, FRACP MB BS Syd PhD Melb

Senior Postdoctoral Fellow: Gabrielle Goldberg, BSc(Hons) Mon PhD Mon

Postdoctoral Fellow: Willy-John Martin, BSc MSc Waikato PhD Wellington

Research Assistant:Yen Huynh

Research Assistant: Jane Murphy, BSc(Hons) Adelaide

Research Assistant: Annemarie van Nieuwenhuijze, BSc MSc Amsterdam

Postgraduate Student: Simon Chatfield, MB BS Melb

Postgraduate Student: Xiao (Tommy) Liu BSc Otago MSc VUT

Scientific Coordinator: Rhiannon Jones BSc(Hons) PhD Adelaide