| Module Leaders |
Professor Richard Boyd |
|
Dr Ann Chidgey
|
Host Organisation
|
Monash Immunology and Stem Cell Laboratories (MISCL), Monash University
|
Module description
This project focuses on defining the nature of adult thymus epithelial stem cells and their contribution to the establishment, homeostatic maintenance and, most importantly, repair of the thymus. It also investigates the nature of the stromal niche(s) regulating thymic epithelial stem cell integrity and function, and the ability of mesenchymal stem cells to both minimise damage and hasten recovery of the thymus following common cytoablative therapies for cancer, and immunosuppressive drugs in the transplant setting.
This module has as its origins, the fact that paradoxical to its fundamental importance in generating a fully competent immune system, the thymus undergoes profound atrophy relatively early in life, this being physically evident from puberty and functionally manifest as reduced output of new T cells. The direct consequence of this is a progressively restricted naïve T cell repertoire capable of responding to new challenge. A poorly functioning thymus also severely restricts the abiity to generate long term, low morbidity tolerance to foreign transplants including those of stem cell origin. This module approaches the major unmet clinical need for thymic rejuvenation, by establishing a thorough knowledge of adult thymus stem cells and the factors which influence their maintenance and function. It should provide a basis for overcoming thymic atrophy and hence development of more strategic therapies for immunological-based diseases.
Aims
- To determine the identity of adult thymic epithelial stem cells.
- To characterise the thymic epithelial stem cell niche.
- To investigate the ability of mesenchymal stem cells (MSC) to restore thymic stromal niches, and hence stem cell function, following thymus damage.
Module Leader biographies
Professor Richard Boyd is the Director of Monash Immunology and Stem Cell Laboratories (MISCL), where he leads a laboratory of approximately 25 people. He is also Chief Scientific Officer of UK AIM-listed biotechnology company Norwood Immunology, who have supported the translation of his research to clinical trials in Australia and the US. Professor Boyd’s research has focussed on the formation and growth of the immune system and his group identified epithelial stem cells in the embryonic mouse, which could form a thymus after transplantation.
Professor Boyd has published over 220 papers and for over 25 years has had a major role in education of undergraduate and postgraduate students (supervised over 65 BSc Hons and 35 PhD) at Monash University. He has also given many public lectures on immunology and stem cells, and over 500 scientific presentations at national and international conferences, and research institutes.
Dr Ann Chidgey is the Deputy Head of the Immune Regeneration Laboratory at Monash Immunology and Stem Cell Laboratories (MISCL). She is also a scientific consultant for Norwood Immunology Ltd that has part-funded the laboratory’s previous research and clinical trials and a Lecturer in the Department of Immunology, Monash University. She has developed expertise in the field of thymic biology, with particular emphasis on the development and ageing of the thymic microenvironment and strategies for immune regeneration – including research towards identifying thymic epithelial stem cells and rejuvenating the thymic and bone marrow stem cell niche. Dr Chidgey has received a number of research awards in her career as a research scientist, including the Mollie Hollman Medal for best PhD in the Faculty of Medicine 1998 (Monash Uni) and the Australian Commonwealth Centenary Medal for contributions to ‘Women in Science’.
Contact details
Professor Richard Boyd
Dr Ann Chidgey
Selected publications
- Gill, J., Malin, M., Holländer, G.A., and Boyd, R.L. (2002). Generation of a complete thymic microenvironment by MTS 24+ thymic epithelial cells. Nat Immunol. 3: 635 – 642.
- Balciunaite, G., Keller, MP., Balciunaite, E., Piali, L., Zuklys, S., Yves D. Mathieu, Y.D., Gill, J., Boyd, R., Sussman, D.J., and Holländer, G. (2002). Wnt glycoproteins regulate expression of FoxN1, the gene defective in nude mice. Nat Immunol 3: 1102 - 1108.
- Gill, J., Malin, M., Sutherland, J., Gray, D., Goldberg, G., Hollander, G., and Boyd, R.L. (2003) Thymic generation and regeneration. Immunol Rev. 195: 28-50.
- Van den Brink, M., Alpdogan, O. and Boyd, R. (2004). Strategies to enhance T cell reconstitution in immunocompromised patients. Nature Rev Immunol, 4(11): 856- 867.
- Sutherland, J.S., Goldberg, G.L., Hammett, M.V., Uldrich, A.P., Berzins, S.P., Heng, T.S., Blazar, B.R., Millar, J.L., Malin, M.A., Chidgey, A.P., & Boyd, R.L. (2005). Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol, 175: 2741-2753.
- Chidgey, A.P., Layton, D.S., Trounson, A.O., Boyd, R.L. (2008) Tolerance strategies for stem-cell-based therapies. Nature, 453: 330 – 337.
- Chidgey, A.P., Dudakov, J.A., Seach, N., and Boyd, R.L. (2007) Impact of niche aging on thymic regeneration and immune reconstitution. Semin Immunol, 19: 331-340
- Barnard, A.L., Chidgey, A.P., Bernard, C.A., Boyd, R.L. (2008) Androgen depletion increases the efficacy of bone marrow transplantation in ameliorating experimental autoimmune encephalomyelitis. Blood 113: 204 - 213.
- Sutherland, J.S., Spyroglou, L., Muirhead, J.L., Heng, T.S., Prieto-Hinojosa, A., Prince, H.M., Chidgey, A.P., Schwarer, A.P., and Boyd, R.L. (2008) Enhanced immune system regeneration in humans following allogeneic or autologous hemopoietic stem cell transplantation by temporary sex steroid blockade. Clin Cancer Res, 14(4): 1138-1149
- Fletcher, A.L., Lowen, T.E., Sakkal, S., Reiseger, J.J., Hammett, M.V., Seach, N., Scott, H.S., Boyd, R.L., and Chidgey, A.P. (2009) Ablation and Regeneration of Tolerance-Inducing Medullary Thymic Epithelial Cells after Cyclosporine, Cyclophosphamide, and Dexamethasone Treatment. J Immunol 183: 823-831