Professor Ranjeny Thomas

Arthritis Qld Chair of Rheumatology

The University of Queensland Diamantina Institute
Faculty of Medicine
ranjeny.thomas@uq.edu.au
+61 7 344 36960

Overview

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.

Professor Thomas is a graduate of the University of Western Australia. She received her MBBS in 1984, and then trained in Perth as a rheumatologist. She commenced a research fellowship with Peter Lipsky at Southwestern Medical Center, University of Texas in 1990, where she first identified and characterised human circulating dendritic cell precursors. She is now Professor of Rheumatology at University of Queensland Diamantina Institute, Translational Research Institute, consultant Rheumatologist at Princess Alexandra Hospital and fellow of the Australian Academy of Health and Medical Sciences. In 2020 she was awarded Member of the Order of Australia.

Her research is focussed on the study of autoimmune disease and restoration of tolerance. Through this work, she developed and tested the first rheumatoid arthritis vaccine. She has also contributed major insights into the pathogenesis of spondyloarthropathy and autoimmune diabetes, leading to the development of disease biomarkers and innovative immunotherapies. With Uniquest, Ranjeny founded Dendright, which developed antigen-specific (personalised) immunotherapy and companion biomarkers to prevent and treat rheumatoid arthritis. She is funded by the Juvenile Diabetes Research Foundation and the Helmsley Foundation to develop antigen-specific immunotherapy for children with type 1 diabetes.

Research Impacts

1. Antigen-specific immunotherapy. My team and I developed and have a granted patent for a liposome immunotherapy strategy to induce antigen-specific tolerance in rheumatoid arthritis (RA). It is the first to specifically target ACPA autoantibody-positive patients carrying RA-susceptibility gene variants, each identifiable with existing tests. The product, DEN181 was developed by Dendright, the Uniquest spin-off company founded to commercialize the liposome technology, in partnership and option to licence with Janssen-Biotech, the US pharmaceutical subsidiary of Johnson and Johnson, for the indication of RA. DEN-181 completed a single-dose ascending phase 1 clinical trial in RA at PA Hospital in 2019 (PI – Phillip Vecchio). Mechanistic pre-clinical studies were published in Galea et al, JCI Insight 2019.

2. To translate antigen-specific immunotherapy to children with type 1 diabetes, we carried out pre-clinical studies with Emma Hamilton-Williams and Mark Harris. I am PI on a grant to this team from JDRF and the US Leona M. and Harry B. Helmsley Charitable Trust for a clinical trial of liposomes encapsulating NF-kB inhibitor and diabetes-specific peptide in patients with T1D. We are currently undertaking pre-clinical development. Mechanistic pre-clinical studies were published in Bergot et al, J Immunol 2020.

3. Predicting type 1 diabetes in people at risk. Ahmed Mehdi discovered a peripheral blood genomic signature predicting, in the first year of life, children at risk of future T1D (Mehdi et al, JCI Insight, 2018). Thus we found a way to screen infant blood for risk of developing islet autoantibodies. With implementation of a screening test based on our findings, future monitoring programs could then focus on the small proportion of children at greatest risk. The contribution of environmental factors to expression or suppression of the blood signature could now be tested in studies of at-risk children to inform future primary prevention studies.

Kerry Buchanan developed an estimate of beta cell function from clinical features in children with diabetes (estimated C-peptide. Buchanan et al, J Ped Endocrinol 2019). Yassmin Musthaffa developed a test of lymphocyte immune response to proinsulin antigen, which predicts the duration of partial remission, using estimated C-peptide (Musthaffa et al, Clin Transl Immunol 2021).

4. Tumor vaccination. My team developed a nanoparticle immunotherapy that targets tumor antigen to a specific dendritic cell subset that expresses CLEC9A with collaborators at Diamantina Institute (Riccardo Dolcetti, Roberta Mazzieri), AIBN (Anton Middelberg) and Monash University (Mireille Lahoud, Irine Caminschi). This technology stimulates therapeutically-effective tumor-specific immunity in several mouse models (Zeng et al, JCI 2018). We commenced a collaborative partnership in 2017 with Merck & Co to develop technologies for human cancer immunotherapy.

5. Mechanisms of RA. With Hani El-Ganalawy in Canada and Hugh Reid and Jamie Rossjohn at Monash University, we investigated how immune system cells become particularly cross-reactive in Indigenous North Americans, who have 3-5 times the risk of RA compared to Europeans. We found specific HLA genes were responsible for higher risk RA in Indigenous North Americans. HLA genes are used by the body to educate a person’s immune system to control infection, but in people with Rheumatoid Arthritis the process becomes confused. Infection-fighting immune cells become more likely to cross-react with tissue cells as people age. Immune cells responding to HLA genes in North Indigenous Americans were particularly cross-reactive, resulting in RA being more prevalent and with earlier onset (Law et al, Ann Rheum Dis 2017). Understanding the genes and how they contribute to the cause of RA in the Indigenous North American population implies that specific immunotherapies could be designed for this population in the future.

Qualifications

  • MD, The University of Western Australia
  • FRACP
  • MBBS, The University of Western Australia

Publications

  • Zeng, Bijun, Middelberg, Anton P. J., Gemiarto, Adrian, MacDonald, Kelli, Baxter, Alan G, Talekar, Meghna, Moi, Davide, Tullett, Kirsteen M, Caminschi, Irina, Lahoud, Mireille H, Mazzieri, Roberta, Dolcetti, Riccardo and Thomas, Ranjeny (2018). Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy. The Journal of clinical investigation, 128 (5), 1971-1984. doi: 10.1172/JCI96791

  • Mehdi, Ahmed M., Hamilton-Williams, Emma E., Cristino, Alexandre, Ziegler, Anette, Bonifacio, Ezio, Le Cao, Kim-Anh, Harris, Mark and Thomas, Ranjeny (2018). A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes. JCI Insight, 3 (5). doi: 10.1172/jci.insight.98212

  • Scally, Stephen W, Law, Soi-Cheng, Ting, Yi Tian, Heemst, Jurgen Van, Sokolove, Jeremy, Deutsch, Aaron J, Bridie Clemens, E., Moustakas, Antonis K, Papadopoulos, George K, Woude, Diane Van Der, Smolik, Irene, Hitchon, Carol A, Robinson, David B, Ferucci, Elizabeth D, Bernstein, Charles N, Meng, Xiaobo, Anaparti, Vidyanand, Huizinga, Tom, Kedzierska, Katherine, Reid, Hugh H, Raychaudhuri, Soumya, Toes, René E, Rossjohn, Jamie, El-Gabalawy, Hani and Thomas, Ranjeny (2017). Molecular basis for increased susceptibility of Indigenous North Americans to seropositive rheumatoid arthritis. Annals of the Rheumatic Diseases, 76 (11), 1915-1923. doi: 10.1136/annrheumdis-2017-211300

  • Benham, Helen, Nel, Hendrik J., Law, Soi Cheng, Mehdi, Ahmed M., Street, Shayna, Ramnoruth, Nishta, Pahau, Helen, Lee, Bernett T., Ng, Jennifer, Brunck, Marion E. G., Hyde, Claire, Trouw, Leendert A., Dudek, Nadine L., Purcell, Anthony W., O'Sullivan, Brendan J., Connolly, John E., Paul, Sanjoy K., Le Cao, Kim-Anh and Thomas, Ranjeny (2015). Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype–positive rheumatoid arthritis patients. Science Translational Medicine, 7 (290) 290ra87, 290ra87.1-290ra87.11. doi: 10.1126/scitranslmed.aaa9301

  • Baillet, Athan C., Rehaume, Linda, Benham, Helen, O'Meara, Connor P., Armitage, Charles W., Ruscher, Roland, Brizard, Geraldine, Harvie, Marina C. G., Velasco, Jared, Hansbro, Phillip, Forrester, John V., Degli-Esposti, Mariapia, Beagley, Kenneth W. and Thomas, Ranjeny (2015). High Chlamydia burden promotes TNF-dependent reactive arthritis in SKG mice. Arthritis and Rheumatology, 67 (6), 1535-1547. doi: 10.1002/art.39041

  • Rehaume, Linda, Mondot, Stanislas, Aguirre de Cárcer, Daniel, Velasco, Jared, Benham, Helen, Hasnain, Sumaira Zia, Bowman, Jaclyn, Ruutu, Merja, Hansbro, Philip M., McGuckin, Michael, Morrison, Mark and Thomas, Ranjeny (2014). ZAP-70 genotype disrupts the relationship between microbiota and host leading to spondyloarthritis and ileitis in SKG Mice. Arthritis and Rheumatology, 66 (10), 2780-2792. doi: 10.1002/art.38773

  • Benham, Helen, Rehaume, Linda M., Hasnain, Sumaira Z., Velasco, Jared, Baillet, Athan C., Ruutu, Merja, Kikly, Kristine, Wang, Ran, Tseng, Hsu-Wen, Thomas, Gethin P., Brown, Matthew A., Strutton, Geoffrey, McGuckin, Michael A. and Thomas, Ranjeny (2014). Interleukin-23 mediates the intestinal response to microbial beta-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis and Rheumatology, 66 (7), 1755-1767. doi: 10.1002/art.38638

  • Scally, Stephen W., Petersen, Jan, Law, Soi Cheng, Dudek, Nadine L., Nel, Hendrik J., Loh, Khai Lee, Wijeyewickrema, Lakshmi C., Eckle, Sidonia B.G., van Heemst, Jurgen, Pike, Robert N., McCluskey, James, Toes, Rene E., La Gruta, Nicole L., Purcell, Anthony W., Reid, Hugh H., Thomas, Ranjeny and Rossjohn, Jamie (2013). A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. Journal of Experimental Medicine, 210 (12), 2569-2582. doi: 10.1084/jem.20131241

  • Ruutu, Merja, Thomas, Gethin, Steck, Roland, Degli-Esposti, Mariapia A., Zinkernagel, Martin S., Alexander, Kylie, Velasco, Jared, Strutton, Geoffrey, Tran, Ai, Benham, Helen, Rehaume, Linda, Wilson, Robert J., Kikly, Kristine, Davies, Julian, Pettit, Allison R., Brown, Matthew A., McGuckin, Michael A. and Thomas, Ranjeny (2012). β-glucan triggers spondylarthritis and Crohn's disease–like ileitis in SKG mice. Arthritis and Rheumatism, 64 (7), 2211-2222. doi: 10.1002/art.34423

  • Capini, Christelle, Jaturanpinyo, Montree, Chang, Hsin-I, Mutalik, Srinivas, McNally, Alice, Street, Shayna, Steptoe, Raymond, O'Sullivan, Brendan, Davies, Nigel and Thomas, Ranjeny (2009). Antigen-specific suppression of inflammatory arthritis using liposomes. Journal of Immunology, 182 (6), 3556-3565. doi: 10.4049/jimmunol.0802972

View all Publications

Supervision

  • Doctor Philosophy

  • Master Philosophy

  • Master Philosophy

View all Supervision

Available Projects

  • Type 1 diabetes (T1D) is the most common chronic disease of childhood. It is triggered by an immune dysregulation causing T cells to attack the insulin-producing islet b cells in the pancreas. This results in elevated blood-glucose and severe life-long complications. Our laboratory aims to develop a T cell targeted immunotherapy to prevent or treat T1D. For this goal to be successful, better tools are needed to detect and characterise islet-specific T cells in patient blood as a way to monitor responses to immunotherapy. An understanding is needed of how these T cell responses vary between different patient groups. This project aims to develop an approach to personalised immunomonitoring of islet specific T cells using state-of-the-art high-parameter immune profiling, single cell sequencing and clonotype analysis of islet-specific T cells in patient blood. This approach will later be used to characterise how these T cells respond to immunotherapy. The ideal candidate will have prior knowledge and academic achievement in the field of immunology. Coding in R or practical experience in experimental immunology would be desirable. This project is aligned with a National Health and Medical Research Council funded grant and will be co-supervised by Prof Ranjeny Thomas, A/Prof Emma Hamilton-Williams, Dr Ahmed Mehdi and Dr Mark Harris. The supervisory team is highly experienced and provides broad expertise and experience in immunology, bioinformatics, translational and clinical research.

View all Available Projects

Publications

Featured Publications

  • Zeng, Bijun, Middelberg, Anton P. J., Gemiarto, Adrian, MacDonald, Kelli, Baxter, Alan G, Talekar, Meghna, Moi, Davide, Tullett, Kirsteen M, Caminschi, Irina, Lahoud, Mireille H, Mazzieri, Roberta, Dolcetti, Riccardo and Thomas, Ranjeny (2018). Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy. The Journal of clinical investigation, 128 (5), 1971-1984. doi: 10.1172/JCI96791

  • Mehdi, Ahmed M., Hamilton-Williams, Emma E., Cristino, Alexandre, Ziegler, Anette, Bonifacio, Ezio, Le Cao, Kim-Anh, Harris, Mark and Thomas, Ranjeny (2018). A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes. JCI Insight, 3 (5). doi: 10.1172/jci.insight.98212

  • Scally, Stephen W, Law, Soi-Cheng, Ting, Yi Tian, Heemst, Jurgen Van, Sokolove, Jeremy, Deutsch, Aaron J, Bridie Clemens, E., Moustakas, Antonis K, Papadopoulos, George K, Woude, Diane Van Der, Smolik, Irene, Hitchon, Carol A, Robinson, David B, Ferucci, Elizabeth D, Bernstein, Charles N, Meng, Xiaobo, Anaparti, Vidyanand, Huizinga, Tom, Kedzierska, Katherine, Reid, Hugh H, Raychaudhuri, Soumya, Toes, René E, Rossjohn, Jamie, El-Gabalawy, Hani and Thomas, Ranjeny (2017). Molecular basis for increased susceptibility of Indigenous North Americans to seropositive rheumatoid arthritis. Annals of the Rheumatic Diseases, 76 (11), 1915-1923. doi: 10.1136/annrheumdis-2017-211300

  • Benham, Helen, Nel, Hendrik J., Law, Soi Cheng, Mehdi, Ahmed M., Street, Shayna, Ramnoruth, Nishta, Pahau, Helen, Lee, Bernett T., Ng, Jennifer, Brunck, Marion E. G., Hyde, Claire, Trouw, Leendert A., Dudek, Nadine L., Purcell, Anthony W., O'Sullivan, Brendan J., Connolly, John E., Paul, Sanjoy K., Le Cao, Kim-Anh and Thomas, Ranjeny (2015). Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype–positive rheumatoid arthritis patients. Science Translational Medicine, 7 (290) 290ra87, 290ra87.1-290ra87.11. doi: 10.1126/scitranslmed.aaa9301

  • Baillet, Athan C., Rehaume, Linda, Benham, Helen, O'Meara, Connor P., Armitage, Charles W., Ruscher, Roland, Brizard, Geraldine, Harvie, Marina C. G., Velasco, Jared, Hansbro, Phillip, Forrester, John V., Degli-Esposti, Mariapia, Beagley, Kenneth W. and Thomas, Ranjeny (2015). High Chlamydia burden promotes TNF-dependent reactive arthritis in SKG mice. Arthritis and Rheumatology, 67 (6), 1535-1547. doi: 10.1002/art.39041

  • Rehaume, Linda, Mondot, Stanislas, Aguirre de Cárcer, Daniel, Velasco, Jared, Benham, Helen, Hasnain, Sumaira Zia, Bowman, Jaclyn, Ruutu, Merja, Hansbro, Philip M., McGuckin, Michael, Morrison, Mark and Thomas, Ranjeny (2014). ZAP-70 genotype disrupts the relationship between microbiota and host leading to spondyloarthritis and ileitis in SKG Mice. Arthritis and Rheumatology, 66 (10), 2780-2792. doi: 10.1002/art.38773

  • Benham, Helen, Rehaume, Linda M., Hasnain, Sumaira Z., Velasco, Jared, Baillet, Athan C., Ruutu, Merja, Kikly, Kristine, Wang, Ran, Tseng, Hsu-Wen, Thomas, Gethin P., Brown, Matthew A., Strutton, Geoffrey, McGuckin, Michael A. and Thomas, Ranjeny (2014). Interleukin-23 mediates the intestinal response to microbial beta-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis and Rheumatology, 66 (7), 1755-1767. doi: 10.1002/art.38638

  • Scally, Stephen W., Petersen, Jan, Law, Soi Cheng, Dudek, Nadine L., Nel, Hendrik J., Loh, Khai Lee, Wijeyewickrema, Lakshmi C., Eckle, Sidonia B.G., van Heemst, Jurgen, Pike, Robert N., McCluskey, James, Toes, Rene E., La Gruta, Nicole L., Purcell, Anthony W., Reid, Hugh H., Thomas, Ranjeny and Rossjohn, Jamie (2013). A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. Journal of Experimental Medicine, 210 (12), 2569-2582. doi: 10.1084/jem.20131241

  • Ruutu, Merja, Thomas, Gethin, Steck, Roland, Degli-Esposti, Mariapia A., Zinkernagel, Martin S., Alexander, Kylie, Velasco, Jared, Strutton, Geoffrey, Tran, Ai, Benham, Helen, Rehaume, Linda, Wilson, Robert J., Kikly, Kristine, Davies, Julian, Pettit, Allison R., Brown, Matthew A., McGuckin, Michael A. and Thomas, Ranjeny (2012). β-glucan triggers spondylarthritis and Crohn's disease–like ileitis in SKG mice. Arthritis and Rheumatism, 64 (7), 2211-2222. doi: 10.1002/art.34423

  • Capini, Christelle, Jaturanpinyo, Montree, Chang, Hsin-I, Mutalik, Srinivas, McNally, Alice, Street, Shayna, Steptoe, Raymond, O'Sullivan, Brendan, Davies, Nigel and Thomas, Ranjeny (2009). Antigen-specific suppression of inflammatory arthritis using liposomes. Journal of Immunology, 182 (6), 3556-3565. doi: 10.4049/jimmunol.0802972

Book Chapter

  • Thomas, Ranjeny and Cope, Andrew P. (2013). Pathogenesis of rheumatoid arthritis. Oxford Textbook of Rheumatology. (pp. 839-848) edited by Richard A. Watts, Philip G. Conaghan, Christopher Denton, Helen Foster, John Isaacs and Ulf Müller-Ladner. Oxford, United Kingdom: Oxford University Press. doi: 10.1093/med/9780199642489.001.0001

  • Pai, Saparna and Thomas, Ranjeny (2009). Dendritic Cells. Rheumatoid Arthritis. (pp. 116-123) Elsevier Inc.. doi: 10.1016/B978-032305475-1.50021-5

  • Lutzky, Viviana and Thomas, Ranjeny (2007). Dendritic cells. Contemporary Targeted therapies in Rheumatology. (pp. 63-78) edited by Josef F. Smolen and Peter E. Lipsky. UK: Informa Healthcare.

  • Pettit, Allison R., Cavanagh, Lois, Boyce, Amanda, Padmanabha, Jagadish, Peng, Judy and Thomas, Ranjeny. (2007). Identification and isolation of synovial dendritic cells. Arthritis Research Methods and Protocols. (pp. 165-181) edited by Andrew P. Cope. Totowa, N.J., U.S.A.: Humana Press Inc.

  • Thomas, Ranjeny, Thompson, Angus G., Martin, Ela and O'Sullivan, Brendan. J. (2003). Dendritic Cells. Targeted Therapies in Rheumatology. (pp. 61-81) edited by Josef S. Smolen and Peter E. Lipsky. London, UK: Martin Duntiz.

  • Thomas, R. (2001). Dendritic Cells and Autoimmunity. Dendritic Cells. (pp. 459-471) edited by M.T. Lotze and A.W. Thomason. United Kingdom: Academic Press.

  • Pettit, A. R., Cavanagh, L. L. and Thomas, R. (2001). Identification and isolation of synovial dendritic cells. Dendritic Cell Protocols. (pp. 175-187) edited by S. P. Robinson and A. J. Stagg. Totowa USA: Humana Press.

Journal Article

Conference Publication

Other Outputs

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Type 1 diabetes (T1D) is the most common chronic disease of childhood. It is triggered by an immune dysregulation causing T cells to attack the insulin-producing islet b cells in the pancreas. This results in elevated blood-glucose and severe life-long complications. Our laboratory aims to develop a T cell targeted immunotherapy to prevent or treat T1D. For this goal to be successful, better tools are needed to detect and characterise islet-specific T cells in patient blood as a way to monitor responses to immunotherapy. An understanding is needed of how these T cell responses vary between different patient groups. This project aims to develop an approach to personalised immunomonitoring of islet specific T cells using state-of-the-art high-parameter immune profiling, single cell sequencing and clonotype analysis of islet-specific T cells in patient blood. This approach will later be used to characterise how these T cells respond to immunotherapy. The ideal candidate will have prior knowledge and academic achievement in the field of immunology. Coding in R or practical experience in experimental immunology would be desirable. This project is aligned with a National Health and Medical Research Council funded grant and will be co-supervised by Prof Ranjeny Thomas, A/Prof Emma Hamilton-Williams, Dr Ahmed Mehdi and Dr Mark Harris. The supervisory team is highly experienced and provides broad expertise and experience in immunology, bioinformatics, translational and clinical research.