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, Translational Research Institute, consultant Rheumatologist at Princess Alexandra Hospital and fellow of the Australian Academy of Health and Medical Sciences.

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. Ranjeny is founder and a director of the spin-off company, Dendright, which is developing antigen-specific (personalised) immunotherapy and companion biomarkers to prevent and treat rheumatoid arthritis. She is funded by the Juvenile Diabetes Research Foundation to develop antigen-specific immunotherapy for children with type 1 diabetes.

Research Impacts

1. My team and I developed and have a granted patent for a liposome vaccine 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 spin-off company I 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 commenced early-phase clinical trials in RA at PA Hospital in November 2017 (PI – Phillip Vecchio).

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. Our team were awarded a grant 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.

3. Ahmed Mehdi in my team 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, provisional patent filed). Thus we have 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 gene “signature” provides a clear comparison of the overall differences between gene expression in white blood cells of children who progress to antibody development and children who don’t. This information offers insight into early, critical, developmental processes that are dysregulated in type 1 diabetes. The contribution of environmental factors to expression or suppression of the blood signature could now be tested in studies of at-risk children that are going on around the world, to inform future primary prevention studies.

4. 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. With Hani El-Ganalawy in Canada, 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, leading to an attack on the body’s tissues. 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: 290ra87.1-290ra87.11. 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

  • Master Philosophy

  • Doctor Philosophy

  • Master Philosophy

View all Supervision

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: 290ra87.1-290ra87.11. 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. In Richard A. Watts, Philip G. Conaghan, Christopher Denton, Helen Foster, John Isaacs and Ulf Müller-Ladner (Ed.), Oxford Textbook of Rheumatology 4th ed. (pp. 839-848) Oxford, United Kingdom: Oxford University Press. doi:10.1093/med/9780199642489.001.0001

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

  • Lutzky, Viviana and Thomas, Ranjeny (2007). Dendritic cells. In Josef F. Smolen and Peter E. Lipsky (Ed.), Contemporary Targeted therapies in Rheumatology (pp. 63-78) 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. In Andrew P. Cope (Ed.), Arthritis Research Methods and Protocols (pp. 165-181) Totowa, N.J., U.S.A.: Humana Press Inc.

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

  • Thomas, R. (2001). Dendritic Cells and Autoimmunity. In M.T. Lotze and A.W. Thomason (Ed.), Dendritic Cells 2nd ed. (pp. 459-471) United Kingdom: Academic Press.

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

Journal Article

Conference Publication

Other Outputs

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Master Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Master Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Associate Advisor

  • Doctor Philosophy — Associate Advisor

Completed Supervision