The Walter and Eliza Hall Institute of Medical Research

Dr Axel Kallies

Details

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Division: Molecular Immunology

Research Overview

1. Transcriptional and epigenetic regulation of peripheral lymphocyte differentiation
2. The transcriptional network constraining B cell leukaemia development.

Our lab is interested in understanding the molecular events that regulate late lymphocyte differentiation. This process is central to the immune system as it generates the effector populations that determine the ability of our body to control pathogens such as HIV or plasmodium (malaria) and to generate protective immunity after vaccination.

However, the process of lymphocyte differentiation is also intimately linked to autoimmune pathology and leukaemia development. Thus, a thorough understanding of the key molecules involved the peripheral differentiation of B and T cells, the main lymphocytic lineages, is central to any therapeutic approach aimed at treating immunodeficiencies, blood cell-derived cancers or autoimmunity.

Our lab utilises a number of transgenic and knock-out mouse models such as green fluorescent protein (GFP)-based transcription factor reporter mice as well as infection models such as influenza and lymphocytic choriomeningitis virus (LCMV). We are utilising a broad range of molecular techniques including next-generation sequencing, microarrays, real-time PCR and chromatin immunoprecipitation (ChIP).

Research Interests

• Transcriptional and epigenetic regulation of effector and memory T cell differentiation
• Molecular determinants of effector regulatory T cell (Treg) differentiation
• Unravelling the role of Id and E-proteins in B cell to plasma cell differentiation
• Indentifying the distinct roles of transcription factors in B cell leukaemia development.

Applications for PhD and postdoctoral positions are welcome.

Selected Publications

1. Kallies, A., Hasbold, J, Tarlinton, D.M., Dietrich, W., Corcoran, L.M., Hodgkin, P.D. and Nutt, S.L. 2004. Plasma cell ontogeny defined by quantitative changes in Blimp-1 expression. J. Exp. Med. 200: 967-77. (IF=14.6) PMID: 15492122
2. Kallies, A., Hawkins, E.D., Belz, G.T., Metcalf, D., Hommel, M., Corcoran, L.M., Hodgkin, P.D. and Nutt, S.L. 2006. Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self tolerance. Nat. Immunol. 7: 466-74. (IF=27.6). News and Views in Nat. Immunol. 7, 445-6; Research Highlight in Nat. Rev. Immunol. 6, 341; Trends in Immunology 27, 349-51. PMID: 16565720
3. Kallies, A., Hasbold, J., Fairfax, K., Pridans, C., Emslie, D., McKenzie, B.S., Lew, A.M., Corcoran, L.M., Hodgkin, P.D., Tarlinton, D.M. and Nutt, S.L. 2007. Initiation of plasma cell differentiation is independent of Blimp-1. Immunity 26, 555-66. (IF=20.3). Preview in Immunity 26, 543-544; Research Highlight in Nat. Immunol. 8, 685. PMID: 17509907
4. Kallies, A. and Nutt, S.L. 2007. Terminal differentiation of lymphocytes depends on Blimp-1. Curr. Opin. Immunol. 19: 1-7. (IF=11.6) PMID: 17291741
5. Nutt, S.L., Fairfax, K. and Kallies, A. 2007. Blimp-1 guides the fate of effector B and T cells. Nat. Rev. Immunol. 7: 923-7. (IF=28.7) PMID: 17965637
6. D'Costa, C., Emslie, D., Metcalf, D., Smyth, G.K., Karnowski, A., Kallies, A., Nutt, S.L., and Corcoran, L.M. 2009. Blimp1 is limiting for transformation in a mouse plasmacytoma model. Blood 113:5911-9. (IF=10.4) PMID: 19329782
7. Kallies, A., Xin, A., Belz, G.T., Nutt, S.L. 2009. Blimp1 Is Required For The Differentiation Of Protective Effector CD8+ T Cells And Memory Responses. Immunity 31:283-95. (IF=20.3). Preview in Immunity 31:178-80. (corresponding author with S. Nutt) PMID: 19664942
8. Kallies, A. Distinct regulation of effector and memory T cell differentiation. 2008. Immunol. Cell. Biol. 86: 325-32. (IF=3.1) PMID: 18362944
9. Zotos, D, Coquet, JM, Light, A., D'Costa, K, Kallies, A, Corcoran, LM, Godfrey, DI, Smyth,MJ, Nutt, SL, Tarlinton, DM. 2010. IL-21 Regulates Germinal Center B Cell Differentiation and Proliferation Through a B Cell-Intrinsic Mechanism. J. Exp. Med. 207: 365-78.(IF=14.6) PMID: 20142430
10. Kallies A, Carotta S, Huntington ND, Bernard NJ, Tarlinton DM, Smyth MJ, Nutt SL, 2010. A role for Blimp-1 in the transcriptional network controlling natural killer cell maturation. Blood117: 1869-79. (IF=10.1) PMID: 21131593
11. Belz GT and Kallies A. 2010. Effector and Memory CD8+ T cell differentiation: Towards a Molecular Understanding of Fate Determination. Curr. Opin. Immunol. 22: 279-85 (IF=11.6) PMID: 20434894
12. Cretney E, Xin A, Shi W, Minnich M, Masson F, Miasari M, Belz G, SmythGK, Busslinger M, Nutt SL, Kallies A. The transcription factors Blimp1 and IRF4 jointly control differentiation and function of effector regulatory T cells. Nat. Immunol.12: 304-11(IF=27.6) PMID: 21378976
13. Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF, Srivastava M, Divekar DP, Beaton L, Hogan JJ, Fagarasan S, Liston A, Smith KGC, Vinuesa, CG. FoxP3+ follicular regulatory T cells control T follicular helper cells and the germinal center response. Nature Medicine2011 17: 975-82 (IF=27.1) PMID: 21785433

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Current Laboratory Members

Faculty Member: Axel Kallies, PhD Free University Berlin

Postdoctoral Fellow: Mia Miasari, PhD La Trobe

PhD Student: Kevin Man, BSc(Hons) Melb

PhD Student: Annie Xin, BSc(Hons) ANU

Honours Student: Renee Gloury

Overseas Research Trainee: Elien Doorduijn

Overseas Research Trainee: Anna Scherger

Research Assistant: Shoukat Afshar-Sterle, PhD Adelaide