Dr Ray Steptoe
Dr Ray Steptoe

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Associate Professor Ray Steptoe was always interested in science, and began playing with microscopes at age 10. His natural affinity for science eventually led him to study anatomy and human biology at the University of Western Australia (UWA), but he soon realised that learning established knowledge wasn’t enough. He wanted to also generate new scientific knowledge. A PhD in immunology presented the perfect challenge. He found the role of Dendritic Cells (DCs) in the eye particularly interesting.

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 alert the rest of the immune system, primarily via ‘T-cell’ activation. Killer T cells in particular recognise and destroy invaders, while memory T-cells persist after an infection and help maintain immune memory of those specific antigens.

Interestingly, inflammatory immune responses are only rarely triggered in the eye. This is because DCs behave differently there and favour immune tolerance. For Steptoe his work on eye DC sparked an interest in using DCs to selectively induce immune tolerance in autoimmune diseases and inflammatory conditions.
 
After his PhD, he began post-doctoral research at the Thomas E Starzl Transplant Institute at the University of Pittsburgh in the laboratory of Professor Angus Thomson. Organ transplant rejection is an inflammatory immune response and Thomson’s group was the only one in the world looking at the role of DCs in transplant tolerance at the time. Steptoe and his colleagues soon discovered that DCs were important in controlling the outcome of organ transplantation.
 
Steptoe then returned to Australia with his family, and pursued an opportunity to research autoimmune diabetes at the Walter and Eliza Hall Institute of Medical Research in Melbourne. He discovered that DCs can be genetically instructed to turn off the immune response to specific antigens. This finding has advanced the search for clinically applicable ways to turn off the immune response in Type 1 Diabetes (T1D).  
 
In 2004, an opportunity arose for Steptoe to develop an independent research group at The University of Queensland’s Diamantina Institute. He is now a Senior Research Fellow in the Autoimmunity Division at UQDI, and leads a program in immune tolerance. 
 
While still interested in DCs, his focus has recently turned to the immune cells whose behaviour they modulate, memory T-cells in particular. In autoimmune diseases such as T1D, these memory cells confuse ‘self’ antigens with ‘invader’ antigens. As a result they continuously trigger immune reactions that cause ongoing tissue damage.
 
“I really wanted to see the changes that occur in the T-cells as they are turned ‘off’,” Steptoe explains. By determining which genes are activated and deactivated during this process, he hopes to gain a clearer understanding of the biochemical pathways involved in memory T-cell responses. 
 
Associate Professor Steptoe and his UQDI colleagues have recently shown that memory T cells are indeed susceptible to tolerance, moreover he has discovered a unique way of shutting off memory T-cell responses. This approach has therapeutic potential and Associate Professor Steptoe believes it can be used to find a universal ‘off-switch’ in immune memory cells.  There are potential applications in numerous inflammatory conditions.
 
Steptoe looks forward to extending his discoveries into the clinic and believes the collaborations established between UQDI and the Princess Alexandra Hospital are ideal for developing clinical applications of his work. 
 
In the mean time, his awarded Australian Research Council Fellowship and NHMRC grants will enable him valuable access facilities crucial to his research, including a multiphoton microscope. It’s arguably more complex than the microscope he received at age 10, but given the new knowledge he will be able to generate, it’s also a lot more fun.
 

 

Email: r.steptoe@uq.edu.au
Telephone: +61 7 3443 6959

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10 Recent Publications 

Roufaiel, Marian Nassef Kadry Naguib, Wells, James W. and Steptoe, Raymond J. (2015) Impaired T-cell function in B-cell lymphoma: a direct consequence of events at the immunological synapse?. Frontiers in Immunology, 6 JUN: 258.1-258.10. doi:10.3389/fimmu.2015.00258

Foo, Shen Yun, Zhang, Vivian, Lalwani, Amit, Lynch, Jason P., Zhuang, Aowen, Lam, Chuan En, Foster, Paul S., King, Cecile, Steptoe, Raymond J., Mazzone, Stuart B., Sly, Peter D. and Phipps, Simon (2015) Regulatory T cells prevent inducible BALT formation by dampening neutrophilic inflammation. Journal of Immunology, 194 9: 4567-4576. doi:10.4049/jimmunol.1400909

Blake, Stephen J. P., Ching, Alan L. H., Kenna, Tony J., Galea, Ryan, Large, Justin, Yagita, Hideo and Steptoe, Raymond J. (2015) Blockade of PD-1/PD-L1 promotes adoptive T-Cell immunotherapy in a tolerogenic environment. PLoS One, 10 3: . doi:10.1371/journal.pone.0119483

Bergot, Anne-Sophie, Monnet, Nastasia, Tran, Son Le, Mittal, Deepak, Al-Kouba, Jane, Steptoe, Raymond J., Grimbaldeston, Michele A., Frazer, Ian H. and Wells, James W. (2015) HPV16 E7 expression in skin induces TSLP secretion, type 2 ILC infiltration and atopic dermatitis-like lesions. Immunology and Cell Biology, 93 6: 540-547. doi:10.1038/icb.2014.123

Overgaard, Nana H., Jung, Ji-Won, Steptoe, Raymond J. and Wells, James W. (2015) CD4+/CD8+ double positive T cells: more than just a developmental stage?. Journal of Leukocyte Biology, 97 1: 31-38. doi:10.1189/jlb.1RU0814-382

Shah, Neha D., Parekh, Harendra S. and Steptoe, Raymond J. (2014) Asymmetric peptide dendrimers are effective linkers for antibody-mediated delivery of diverse payloads to B cells in vitro and in vivo. Pharmaceutical Research, Online First 11: 3150-3160. doi:10.1007/s11095-014-1408-1

McNally, Alice, McNally, Michael, Galea, Ryan, Thomas, Ranjeny and Steptoe, Raymond J. (2014) Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+T-cell effector differentiation by IL-2 modulation. PloS One, 9 1: . doi:10.1371/journal.pone.0085455

Khairuddin, Norliana, Blake, Stephen J., Firdaus, Farah, Steptoe, Raymond J., Behlke, Mark A., Hertzog, Paul J. and McMillan, Nigel A. J. (2014) In vivo comparison of local versus systemic delivery of immunostimulating siRNA in HPV-driven tumours. Immunology and Cell Biology, 92 2: 156-163. doi:10.1038/icb.2013.75

Forrester, John V., Steptoe, Raymond J., Klaska, Izabela P., Martin-Granados, Cristina, Dua, Harminder S., Degli-Esposti, Mariapia A. and Wikstrom, Matthew E. (2013) Cell-based therapies for ocular inflammation. Progress in Retinal and Eye Research, 35 82-101. doi:10.1016/j.preteyeres.2013.02.002

Coleman, Miranda A., Bridge, Jennifer A., Lane, Steven W., Dixon, Chantelle M., Hill, Geoffrey R., Wells, James W., Thomas, Ranjeny and Steptoe, Raymond J. (2013) Tolerance induction with gene-modified stem cells and immune-preserving conditioning in primed mice: restricting antigen to differentiated antigen-presenting cells permits efficacy. Blood, 121 6: 1049-1058. doi:10.1182/blood-2012-06-434100

 
 
Additional publications:
  1. Wilson NS, Behrens GMN, Lundie RJ, Smith CM, Waithman J, Young L, Forehan SP, Mount A, Steptoe RJ, Shortman KD, de Koning-Ward T, Belz GT, Carbone FR, Crabb BS, Heath WR, Villadangos JA. Systemic activation of dendritic cells by TLR ligands or malaria infection impairs cross-presentation and anti-viral immunity. Nat Immunol. 7:165-172, 2006.
  2. Steptoe RJ, Ritchie JM, Harrison LC. Transfer of hematopoietic stem cells encoding an autoantigen prevents autoimmune diabetes. J Clin Invest. 111:1357-1363, 2003.

 

Dr Steptoe’s research interests are aimed at determining the cellular and molecular pathways that are important in determining the fate of T-cell activation. In particular, studies are directed at understanding how to terminate pathogenic T cell responses with the goal of developing new therapeutic approaches to prevent or treat autoimmune diseases.

  • Cellular and molecular pathways of T-cell tolerance
  • Prevention and reversal of autoimmune diabetes
  • Novel methods of gene delivery for tolerance
  • Immunotherapy of allergies and anaphylaxis