Many mechanisms have evolved to ensure that the immune system does not attack our own tissues; a property referred to as immunological tolerance. The main goal of our team is to understand how to modify tolerance mechanisms to create new ways to treat cancer and autoimmune diseases.
A major project focuses on understanding how defects in cell death and immune homeostasis engender disease. We employ novel pre-clinical models, high dimensional cytometry and advanced imaging approaches to address how these processes shape the development and function of T cells in health and disease.
Australia, Monash University, BSc (Hons), 1998
Australia, Monash University, PhD, 2003
USA, Harvard Medical School, postdoctoral fellow, 2005-2008
2019, Senior Research Fellowship A #1158024, National Health and Medical Research Council
2020, CIA Ideas Grant #1187367, National Health and Medical Research Council
2019, SERP Grant, Leukaemia Foundation
2019, Perpetual Impact Philanthropy Grant
2019, Servier Pharmaceuticals
2018, CIA Project Grant #1145888, National Health and Medical Research Council
Editorial Board, Frontiers in Immunological Tolerance
Member of Faculty of 1000 Prime
VCCC Immunotherapy Program Steering Committee
Weeden, C. E., Gayevskiy, V., Marceaux, C., …, Mackay L., Speed, T. P., Gray, D. H. D.*., Asselin-Labat ML*. (*equal contribution) (2023) Early immune pressure imposed by tissue resident memory T cells sculpts tumour evolution in non-small cell lung cancer. Cancer Cell(accepted)http://dx.doi.org/10.2139/ssrn.4187262
Policheni AN, Teh CE, Robbins AK, Tuzlak S, Strasser A, Gray DHD. PD-1 cooperates with AIRE-mediated tolerance to prevent lethal autoimmune disease. Proc Natl Acad Sci U S A Apr 12;119(15):e2120149119. doi: 10.1073/pnas.212019119. Epub 2022 Apr 8. PMID: 35394861
Teh CE*, Preston SP*, Robbins AK, Stutz MD, … Kallies A, Strasser A, Pellegrini M*, Gray DHD* (* equal contribution). Caspase-8 has dual roles in regulatory T cell homeostasis balancing immunity to infection and collateral inflammatory damage. Sci Immunol. 2022 Mar 25;7(69):eabn8041. doi: 10.1126/sciimmunol.abn8041. Epub 2022 Mar 25 PMID: 35333545
Melanie Heinlein, Luke C Gandolfo, Kelin Zhao, Charis E Teh, Nghi Nguyen, Jonathan B Baell, Yael Goldfarb, Jakub Abramson, Johannes Wichmann, Anne K Voss, Andreas Strasser, Gordon K Smyth, Tim Thomas, Daniel H D Gray. The acetyltransferase KAT7 is required for thymic epithelial cell expansion, expression of AIRE target genes, and thymic tolerance. Sci Immunol. 2022 Jan 21;7(67):eabb6032. doi: 10.1126/sciimmunol.abb6032. Epub 2022 Jan 21. PMID: 35061506
Jain R., Zhao K., Sheridan J.M., Heinlein M., Kupresanin F., Abeysekera W., Hall C., Rickard J., Bouillet P., Walczak H., Strasser A., Silke J. and Gray D.H.D. Dual roles for LUBAC signaling in thymic epithelial cell development and survival. Cell Death and Differentiation, Aug 11 doi 10.1038/s41418-021-00850-8. PMID:34381167
Teh, C.E., Gong, J.N., Segal, D., Tan, T., Vandenberg, C.J., Fedele, P.L., Low, M.S.Y., Grigoriadis, G., Harrison, S.J., Strasser, A., Roberts, A.W., Huang, D.C.S., Nolan, G.P.*,#, Gray, D.H.D.*,#, and Ko, M.E*. Deep profiling of apoptotic pathways with mass cytometry identifies a synergistic drug combination for killing myeloma cells. (* co-senior author; # corresponding authors) Cell Death and Differentiation. 2020 Jul;27(7):2217-2233. doi: 10.1038/s41418-020-0498-z. PMID:31988495
Jain, R., Sheridan, J.M., Policheni, A., Heinlein, M., Gandolfo, L.C., Dewson, G., Smyth, G.K., Sansom, S.N., Fu, N.Y., Visvader, J.E., Hollander, G.A., Strasser, A., and Gray, D.H.D. A critical epithelial survival axis regulated by MCL-1 maintains thymic function in mice. Blood 2017, Dec 7;130(23):2504-2515. Doi: 10.1182/blood-2017-03-771576. PMID:28972012
Teh, C.E., Lalaoui, N., Jain, R., Policheni, A.N., Heinlein, M., Alvarez-Diaz, S., Sheridan, J.M., Rieser, E., Deuser, S., Darding, M., Koay, H.-F., Hu, Y., Kupresanin, F., O’Reilly, L.A., Godfrey, D.I., Smyth, G.K., Bouillet, P., Strasser, A., Walczak, H., Silke, J., and Gray, D.H.D. Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis. Nature Communications 2016; 7: 13353. Doi: 10.1038/ncomms13353. PMID:27857075
Liston, A., and Gray, D.H.D. Homeostatic control of regulatory T cell diversity. Nature Reviews Immunology 2014; 14(3): 154-65. PMID: 24481337
Pierson, W., Cauwe, B., Policheni, A., … Weaver, C.T., Dooley, J., Gray, D.H.D.*, and Liston, A.* (joint senior/corresponding authors) Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3(+) regulatory T cells. Nature Immunology 2013; 14(9): 959-65. PMID:23852275
FOXP3+ regulatory T (Treg) cells are essential for restraining immune function. Their antagonism of autoimmune responses is crucial for health, but they also block responses to chronic infection and cancer. We are interested in how cell death processes shape the homeostasis of Treg cells with a view to modifying them to tailor immune responses. We have discovered the molecular control of Treg cell apoptosis under steady-state conditions (papers #2, 6, 7, 8) and recently defined a new pathway controlling the population during inflammation. This project will explore how to engage Treg cell death to improve responses to cancer and infection.
Dr Charis Teh, Dr Lucille Rankin, Dr Alissa Robbins
In this project, we aim to direct new therapies for treating chronic lymphocytic leukaemia (CLL) and other blood cancers by using CyTOF and high parameter flow cytometry to resolve cell death pathways in millions of individual cancer cells from patients. By understanding how cancerous cells are impacted by new targeted therapies and adapt to resist them, we will be able to inform more effective treatments for CLL and other blood cancers (papers #3, 4).
Dr Charis Teh, Ms Tania Tan, Ms Mengxiao Luo
The thymus is the exclusive site for differentiation of haematopoietic progenitors into the various T cell lineages. Curiously, although the thymus is essential for adaptive immunity, it is easily damaged and undergoes age-related atrophy to become virtually non-functional in adults. However, the thymus can be induced to regenerate and restore T cell immunity. This project focuses on the unique epithelial cells of the thymus that govern these processes. We use cutting edge imaging approaches to resolve how the thymic epithelium changes during involution and thymic regeneration to better understand how immune function might be restored (papers #1 and #5).
Ms Kelin Zhao