Professor Ranjeny Thomas
|Professor Ranjeny Thomas|
Arthritis Queensland Chair in Rheumatology
When she was a child, Ranjeny Thomas didn’t want to be a scientist. She confesses she was drawn instead to the creative arts. But as it turns out, it is precisely her natural creativity, combined with a love of a good mystery, which has led her to become one of Australia’s foremost immunologists.
As a student at the University of Western Australia (UWA), Thomas studied medicine primarily for the career options it offered, but soon found herself searching for a subject that would satisfy both her creativity and curiosity. She found it during her rheumatology training when a visiting Immunology Fellow was invited to help her study group.
“A whole new world opened up to me,” she says. Thomas’ interest in immunology led her to undertake a doctorate at UWA where she discovered her niche at the intersection of laboratory research and clinical Rheumatology practice.
As her work progressed, the puzzle of autoimmune diseases like rheumatoid arthritis (RA) became even more enticing. What was causing the immune system to turn on benign tissues in the body? Her search for a solution led her to the laboratory of the preeminent US immunologist Peter Lipsky at the University of Texas Southwestern Medical Center.
“Peter told me I had to work on healthy humans in order to understand RA, and suggested I look at dendritic cells.”
Dendritic cells (DCs) are part of the immune system’s early response to invasion. They engulf intruders, like bacteria or viruses, and break them down into small parts, called antigens. The DC then presents the antigens on its surface, and uses them to activate helper T cells, which in turn alert the rest of the immune system.
At the time, little was known about the role DCs play in autoimmune diseases, but Thomas made the crucial discovery that DCs help trigger RA by mistaking joint tissue as foreign and erroneously ‘teaching’ T cells to attack. After Thomas returned to Australia she reasoned that if DCs were part of the problem, they could be part of the solution. In 2003, at University of Queensland’s Centre for Immunology and Cancer Research, she and her colleagues discovered that a protein called RelB acts as the switch that allows DCs to teach the immune system to attack.
They then found a way to modify DCs to silence the immune system. Thomas’ new goal was to find a way to use dendritic cells in a therapy for RA. This breakthrough led to the eventual development of a vaccine technology, which turns off the unwanted immune response in RA. In 2005 she founded the Uniquest-owned spin-off company Dendright to focus on commercial development of this technology. UniQuest recently announced a strategic research collaboration agreement with Janssen-Cilag Pty Ltd in Australia, to develop the RA vaccine technology.
Ranjeny Thomas, now Professor of Rheumatology at UQ and head of the Autoimmunity Division at the UQ Diamantina Institute, continues to work on dendritic cells and autoimmune diseases. In addition to her progress in RA, her work has advanced understanding of diabetes and ankylosing spondylitis. Already this has led her to develop both a diagnostic test for juvenile diabetes.
Thomas looks forward to finding more creative ways to unlock the mysteries of the immune system and develop new treatments for autoimmune disease.
“Immunology research has reached a very exciting stage, where the development of new ‘designer therapies’ for prevention and treatment of inflammatory diseases that affect the life of millions of people across the world is becoming a real possibility. It’s both a privilege and an enormous challenge to be a part of that!”
Phone: +61 7 3443 6960
- Dr Allison Pettit (PhD student): Senior Research fellow, Mater-UQ Research Institute, Brisbane.
- Dr Kelli MacDonald (Post-doc): Group leader, QIMR, Brisbane.
- Dr Athan Baillet (post-doc): Assistant chef de clinique, Rheumatologie, University Joseph Fourier-Grenoble, France
- Dr Helen Benham (PhD student): Staff Rheumatologist, Princess Alexandra Hospital and Lecturer and Deputy Head of Southern Clinical School, University of Queensland
- Dr Judy Peng (PhD student): Editor, Frontiers in Immunology, Germany.
- Dr Angus Thompson (MBBS-PhD student): Consultant Cardiologist, Perth, Western Australia.
- Dr Simone Zehntner (post-doc): Assistant Director and Research Associate, Small Animal Imaging Lab, McConnell Brain Imaging Center, McGill University, Montreal, Canada.
- Dr Fengxiao Zhang (fellow): Director of Department of Rheumatology and Clinical Immunology, Hebei Provincial People's Hospital, China
Pang, Dimeng, Irvine, Katharine M., Mehdi, Ahmed M., Thomas, Helen E., Harris, Mark, Hamilton-Williams, Emma E. and Thomas, Ranjeny (2015) Expression profiling pre-diabetic mice to uncover drugs with clinical application to type 1 diabetes. Clinical and Translational Immunology, 4 8: e41.1-e41.9. doi:10.1038/cti.2015.17
Koning F*, Thomas R*, Rossjohn J* and R Toes*. From celiac disease to rheumatoid arthritis: common mechanisms, different antigens. Nat Rev Rheum 2015 doi: 10.1038/nrrheum.2015.59
Benham H*, Nel HJ*, Law SC*, Mehdi AM*, Street S, Ramnoruth N, Pahau H, Lee BT, Ng J, Brunck MEG, Hyde C, Trouw LA, Dudek NL, Purcell AW, O’Sullivan BJ, ConnollyJE, Paul S, Lê Cao KA and R Thomas.Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients. Science Transl Med 2015, 7:290ra87
Baillet AC, Rehaume LM, Benham H, O’Meara C, Armitage C, Brizard G, Harvie M, Bowman J, Velasco J, Forrester J, Degli-Esposti MA, Beagley K and R Thomas. Reactive arthritis in SKG mice results from a dysfunctional T cell response and an exaggerated inflammatory response to Chlamydia muridarum infection.Arthritis Rheumatol 2015 doi: 10.1002/art.39041.
Anderson A*, Pratt AG*, Sedhom MAK*, Doran J.P., Routledge C, Hargreaves B., Brown, P.M. Isaacs J, R. Thomas. IL-6 driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anti-citrullinated peptide antibody-negative rheumatoid arthritis. Ann Rheum Dis 2015 doi: 10.1136/annrheumdis-2014-205850.
Rehaume LM, Aguirre D, Velasco J, Ruutu MP, Mondot S, Morrison M, McGuckin MA, Thomas R. ZAP-70 genotype disrupts the relationship between microbiota and host leading to spondyloarthritis and ileitis.Arthritis Rheum 2014, 66; 2780-92
Benham H, Rehaume LM, Hasnain S, Velasco J, Baillet A, Ruutu MP, Kikly K, Brown MA, Strutton G, McGuckin MA and R Thomas. IL-23-mediates the intestinal response to microbial beta-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis Rheum 2014, 66:1755-67.
Videm, Vibeke, Cortes, Adrian, Thomas, Ranjeny and Brown, Matthew A. (2014) Current smoking is a risk factor for incident ankylosing spondylitis – HUNT population-based Norwegian health study.. Journal of Rheumatology, 41 10: 2041-2048. doi:10.3899/jrheum.140353
Thomas R. Dendritic cells and the promise of antigen-specific therapy in rheumatoid arthritis. Arthritis Res Ther 2013, 15:204
Scally SW, Petersen J, Law SC, Dudek N, Nel HJ, Loh KL, Wijeyewickrema LC, Eckle S, Pike RN, McCluskey J, Toes RE, La Gruta NL, Purcell AW*, Reid HH*, Thomas R* and J Rossjohn*. A molecular basis for the association of the HLA-DRB1 locus, citrullination and rheumatoid arthritis. J Exp Med 2013,210:2569-82
Irvine K, Gallego P, An X, Denny J, Baskerville T, Flynn S, Thomas G, Wells C, Harris M, Cotterill A and R Thomas. Peripheral blood monocyte gene expression profile clinically stratifies patients with recent onset Type 1 Diabetes. Diabetes 2012, 61:1281-1290
Law SC, Street S, Yu CHA, Capini C, Ramnoruth S, Nel HJ, van Gorp E, Hyde C, Lau K, Purcell AW and R Thomas. T cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles. Arthritis Res Ther 2012;14:R118
Ruutu M, Thomas G, Steck Roland, Degli-Esposti, MA, Zinkernagel MS, Alexander K, Velasco J, Strutton G, Tran A, Pettit A, Benham H, Rehaume L, Wilson RJ, Kikly K, Davies J, McGuckin M, Brown MA and R Thomas. Beta-glucan triggers spondyloarthropathy and Crohn’s-like ileitis in SKG mice. Arthritis Rheum 2012, 64:2211-22.
Shklovskaya E, O’Sullivan BJ, Ng LG, Roediger B, Thomas R, Weninger W and B Fazekas de St Groth. Langerhans cells are pre-committed to immune tolerance induction. Proc Natl Acad USA 2011;108:18049-18054
O’Sullivan BJ*, Pai S*, Street S, An X, MacDonald KP, Wong M, Strutton G, Gerondakis S, Steptoe RJ, Hill GR and R Thomas. Immunotherapy with costimulatory dendritic cells to control autoimmune inflammation. J Immunol 2011;187:4018-30
Capini C, Jaturanpinyo M, Chang HI, Mutalik S, Street S, O’Sullivan BJ, Davies NM and R Thomas. Antigen-specific suppression of inflammatory arthritis using liposomes. J Immunol 2009 182:3556-65
Isomura I, Palmer S, Grumont RJ, Bunting K, Hoyne G, Wilkinson N, Banerjee A, Proietto A, Gugasyan R, Li W, McNally A, Steptoe R, Thomas R, Shannon MF and S Gerondakis. c-Rel is required for the development of thymic Foxp3+ CD4 regulatory T cells. J Exp Med 2009, 206:3001-14.
Professor Thomas’ research is focused on the study of the biology and clinical use of human dendritic cells in autoimmune disease. It has explored basic mechanisms of immunity and dendritic cell function in autoimmune disease. This has given rise to several clinical applications, including:
- An antigen-specific vaccine to treat rheumatoid arthritis, currently in clinical trials
- A therapeutic platform for antigen-specific immunotherapy
- A novel diagnostic test for identification of those at risk of type 1 (juvenile) diabetes
- Novel immunotherapy for type 1 diabetes
Research projects span from understanding dendritic cell function through analysis of signaling pathways, in vivo studies of tolerance, through to clinical trials of tolerance in autoimmunity, and clinical studies of risk factors in rheumatoid arthritis and type 1 diabetes.
- Understanding the molecular control of dendritic cell function in tolerance
- Pathogenesis of inflammatory bowel disease, psoriasis, uveitis and arthritis in a mouse model of spondyloarthropathy: microbiota and the interaction with host immunity
- Rheumatoid arthritis antigen-specific therapy: mouse models
- Antigen-specific T cells in Rheumatoid Arthritis: MHC-peptide interactions with T cells
- Type 1 (Juvenile) Diabetes novel treatments: mouse models
- Type 1 diabetes biomarkers: human longitudinal study