Prof Ian Wicks, Lab Head | WEHI Researcher Profile

Q: Cytokine antagonists in rheumatoid arthritis

Rheumatoid arthritis (RA) is a common human inflammatory disease that targets synovial joints, causing chronic joint pain and leading to joint damage and progressive disability. The cause of RA remains unclear, although activation of innate and adaptive immune systems and increased production of cytokines are prominent features of RA. We aim to understand the biology of key effector cells and dysregulation of cytokine production and cytokine signalling in RA, in order to identify new therapeutic targets and biomarkers to more effectively treat RA. We have established a wide range of experimental systems to study RA, employing WEHI's advanced technologies. In conjunction with the Centre for Biologic Therapies, we are developing several therapeutic antibodies to new targets.

Q: Kawasaki disease and temporal arteritis

Kawasaki Disease (KD) causes cardiac vasculitis in children. Temporal arteritis (also called giant cell arteritis, GCA) is a similar condition in older adults. We have established an experimental model of KD and have been determining which cells and cytokines are the most suitable candidates for therapeutic intervention. We showed that GM-CSF is a critical cytokine in KD. Based on this and other research, an anti-GM-CSF receptor antibody has undergone clinical trials in GCA. We have also recently identified the mTOR pathway and its inhibitor rapamycin as another important pathway in KD.

Q: Molecular pathology of myositis

Myositis comprises a spectrum of poorly understood inflammatory diseases involving muscles. This is a new area of research for the Lab, employing in vitro and in vivo experimental models and advanced technologies, including spatial transcriptomics applied to human muscle biopsies.

Q: Hemolytic disease of the newborn (HDN)

Rhesus D incompatability between mother and baby is a well recognised cause of HDN. remarkably, it can be largely prevented by administration of pooled anti-RhD immunoglobulins during pregnancy, derived from blood donors. As part of our Lab's interests in therapeutic antibodies, we are collaborating with Australian Red Cross Lifeblood to fully characterise these naturally occurring anti-RhD antibodies.

About

My lab research is focused on molecular analysis of inflammatory and autoimmune diseases. We use murine and human experimental systems and apply ‘omics’ technologies in order to improve understanding of disease pathogenesis, find better biomarkers and develop targeted therapeutics.

Our primary focus has been on rheumatoid arthritis (RA), but we’ve found that experimental systems and techniques used to study RA are relevant to many other inflammatory diseases, and we now have active research programs in vasculitis, myositis and lupus. We also have a strong interest in developing therapeutic antibodies and several of these have gone into clinical trials. In addition to engineered antibodies, we have formed a collaboration with Australian Red Cross Lifeblood to study the naturally occurring human antibody repertoire in hemolytic disease of the newborn.

A major research theme of my lab is to investigate how the cytokines G-CSF and GM-CSF promote inflammatory diseases. This has led to collaborations with the biotechnology sector (CSL, MedImmune and Kiniksa) and the development of antibody-based therapies to the G- and GM-CSF receptors that are currently in clinical trials.

Skills and expertise:
– Human inflammatory and immune-mediated diseases, including clinical trials
– Experimental models of inflammatory diseases
– Antibody-based therapies

Education

Joint appointments

Grants and funding

Publications

Selected publications from Prof Ian Wicks

Heydarchi B, D’Silva DB, Wong HL, Goddard-Borger ED, Wicks IP. Fc mutagenesis enhances the functionality of anti-RhD monoclonal antibodies. Blood Advances. 2024;:10.1182/bloodadvances.2024015082

Wicks I. Vagus. BioScience. 2024;74(10):10.1093/biosci/biae021

Oxley EP, Kershaw NJ, Louis C, Goodall KJ, Garwood MM, Jee Ho SM, Voo VTF, Park H-Y, Iaria J, Wong LLL, Lebenbaum AG, Wiranata S, Pang ES, Edwards ESJ, D’Silva DB, Hansen J, van Zelm MC, O’Keeffe M, Hogarth PM, Haynes NM, Huntington ND, Wicks IP, Dickins RA. Context-restricted PD-(L)1 checkpoint agonism by CTLA4-Ig therapies inhibits T cell activity. Cell Reports. 2024;43(10):10.1016/j.celrep.2024.114834

Maxwell S, Ross L, Oon S, Wicks IP, Day J. Muscle biopsy practices in the evaluation of idiopathic inflammatory myopathies: An international survey of expert clinicians. Seminars in Arthritis and Rheumatism. 2024;68:10.1016/j.semarthrit.2024.152519

Stock AT, Parsons S, Hansen JA, D’Silva DB, Starkey G, Fayed A, Lim XY, D’Costa R, Gordon CL, Wicks IP. mTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis. EMBO Reports. 2024;25(10):10.1038/s44319-024-00251-1

Chiou S, Al-Ani AH, Pan Y, Patel KM, Kong IY, Whitehead LW, Light A, Young SN, Barrios M, Sargeant C, Rajasekhar P, Zhu L, Hempel A, Lin A, Rickard JA, Hall C, Gangatirkar P, Yip RK, Cawthorne W, Jacobsen AV, Horne CR, Martin KR, Ioannidis LJ, Hansen DS, Day J, Wicks IP, Law C, Ritchie ME, Bowden R, Hildebrand JM, O’Reilly LA, Silke J, Giulino-Roth L, Tsui E, Rogers KL, Hawkins ED, Christensen B, Murphy JM, Samson AL. An immunohistochemical atlas of necroptotic pathway expression. EMBO Molecular Medicine. 2024;16(7):10.1038/s44321-024-00074-6

Aymonnier K, Bosetta E, Leborgne NGF, Ullmer A, Le Gall M, De Chiara A, Salnot V, Many S, Scapini P, Wicks I, Chatfield S, Martin KR, Witko-Sarsat V. G-CSF reshapes the cytosolic PCNA scaffold and modulates glycolysis in neutrophils. Journal of Leukocyte Biology. 2024;115(2):10.1093/jleuko/qiad122

Martin KR, Gamell C, Tai TY, Bonelli R, Hansen J, Tatoulis J, Alhamdoosh M, Wilson N, Wicks I. Whole blood transcriptomics reveals granulocyte colony‐stimulating factor as a mediator of cardiopulmonary bypass‐induced systemic inflammatory response syndrome. Clinical & Translational Immunology. 2024;13(2):10.1002/cti2.1490

Garnish SE, Martin KR, Kauppi M, Jackson VE, Ambrose R, Eng VV, Chiou S, Meng Y, Frank D, Tovey Crutchfield EC, Patel KM, Jacobsen AV, Atkin-Smith GK, Di Rago L, Doerflinger M, Horne CR, Hall C, Young SN, Cook M, Athanasopoulos V, Vinuesa CG, Lawlor KE, Wicks IP, Ebert G, Ng AP, Slade CA, Pearson JS, Samson AL, Silke J, Murphy JM, Hildebrand JM. A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation. Nature Communications. 2023;14(1):10.1038/s41467-023-41724-6

Mian M, Lim BG, Hossain N, Wicks I, Day J. Retrospective comparison of ultrasound guided percutaneous and open skeletal muscle biopsies. Internal Medicine Journal. 2023;53(8):10.1111/imj.15885