he aim of the Thomas laboratory is to understand how the balance between proliferation and differentiation of stem cells is maintained.
One important aspect of this is to define the role of co-activators of transcription in stem and progenitors cells during embryonic development and in adults. We are particularly interested in the function of the MYST family of histone acetyltransferases in stem cell populations. We have shown that KAT6A (MOZ) is essential for the development of haematopoietic stem cells whereas KAT6B (QKF) has an essential role in adult neural stem cells.
We are currently investigating the function of the MYST family, particularly KAT6A and KAT6B, during embryonic development and in adult stem cell populations.
The Thomas lab has a long-term interest in understanding the epigenetic regulation of embryonic development and in particular has characterised the function of histone acetyltransferases. These chromatin modifiers are important regulators of development and deregulated in cancer. More recently, Tim has completed a drug discovery project, developing acetyltransferase inhibitors and a new class of anti-cancer therapeutics.
Australia, The University of Melbourne, PhD
2021 Australian Academy of Technological Science & Engineering Clunies Ross Award (Knowledge Commercialisation)
2021 Victoria Prize for Science and Innovation in the Life Sciences
2018 Kellaway Discovery Award
1995 Max Planck Society Research Fellowship
1993 EMBO Fellowship
2019 – 2022 Acquisition of long-term self-renewal by hematopoietic progenitors, National Health and Medical Research Council
2019 – 2022 Unique and shared functions of KAT6A and KAT6B, National Health and Medical Research Council
2018 – 2020 The molecular and biological roles of growth inhibiting chromatin binding proteins, National Health and Medical Research Council
2015 – 2017 The role of Moz, monocytic zinc finger gene, in the pathogenesis of leukaemia, National Health and Medical Research Council
2015 – 2017 TAF8 is a suppressor of cell death, National Health and Medical Research Council
2015 – 2017 Chromatin regulation of neural stem cell multipotency, National Health and Medical Research Council
2015 – 2017 Regulation of haematopoietic stem cells through histone modifications, National Health and Medical Research Council
2015 – 2017 Unique and selective small molecules to dissect histone acetyltransferase biology, National Health and Medical Research Council
Yang Y, Kueh AJ, Grant ZL, Abeysekera W, Garnham AL, Wilcox S, Hyland CD, Di Rago L, Metcalf D, Alexander WS, Coultas L, Smyth GK, Voss AK*, Thomas T*. The histone lysine acetyltransferase HBO1 (KAT7) regulates hematopoietic stem cell quiescence and self-renewal. Blood. 2022 Feb 10;139(6):845-858. PMID: 34724565
McRae HM, Garnham AL, Hu Y, Witkowski MT, Corbett MA, Dixon MP, May RE, Sheikh BN, Chiang W, Kueh AJ, Nguyen TA, Man K, Gloury R, Aubrey BJ, Policheni A, Di Rago L, Alexander WS, Gray DHD, Strasser A, Hawkins ED, Wilcox S, Gécz J, Kallies A, McCormack MP, Smyth GK, Voss AK, Thomas T. PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia. Blood. 2019 Apr 18;133(16):1729-1741. PMID: 30755422
Baell JB, Leaver DJ, Hermans SJ, Kelly GL, Brennan MS, Downer NL, Nguyen N, Wichmann J, McRae HM, Yang Y, Cleary B, Lagiakos HR, Mieruszynski S, Pacini G, Vanyai HK, Bergamasco MI, May RE, Davey BK, Morgan KJ, Sealey AJ, Wang B, Zamudio N, Wilcox S, Garnham AL, Sheikh BN, Aubrey BJ, Doggett K, Chung MC, de Silva M, Bentley J, Pilling P, Hattarki M, Dolezal O, Dennis ML, Falk H, Ren B, Charman SA, White KL, Rautela J, Newbold A, Hawkins ED, Johnstone RW, Huntington ND, Peat TS, Heath JK, Strasser A, Parker MW, Smyth GK, Street IP, Monahan BJ, Voss AK*, Thomas T*. Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth. Nature. 2018 Aug;560(7717):253-257.PMID: 30069049
Sheikh BN, Yang Y, Schreuder J, Nilsson SK, Bilardi R, Carotta S, McRae HM, Metcalf D, Voss AK*, Thomas T*. MOZ (KAT6A) is essential for the maintenance of classically defined adult hematopoietic stem cells. Blood. 2016 Sep 23. . PMID: 27663673
Sheikh BN, Lee SC, El-Saafin F, Vanyai HK, Hu Y, Pang SH, Grabow S, Strasser A, Nutt SL, Alexander WS, Smyth GK, Voss AK*, Thomas T*. MOZ regulates B cell progenitors and, consequently, Moz haploinsufficiency dramatically retards MYC-induced lymphoma development. Blood. 2015 125(12):1910-1921. PMID: 25605372
Sheikh BN, Phipson B, El-Saafin F, Vanyai HK, Downer NL, Bird MJ, Kueh AJ, May RE, Smyth GK, Voss AK*, Thomas T*. MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway. Oncogene. 2015 34(37):5807-5820. PMID: 25772242
Voss AK, Vanyai HK, Collin C, Dixon MP, McLennan TJ, Sheikh BN, Scambler P, Thomas T. MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome. Dev Cell. 2012 Sep 11;23(3):652-63. PMID: 22921202
Kueh AJ, Dixon MP, Voss AK*, Thomas T*. HBO1 is required for H3K14 acetylation and normal transcriptional activity during embryonic development. Mol Cell Biol. 2011 Feb;31(4):845-60. PMID: 21149574
Voss AK, Collin C, Dixon MP, Thomas T. Moz and retinoic acid coordinately regulate H3K9 acetylation, Hox gene expression, and segment identity. Dev Cell. 2009 Nov;17(5):674-86. PMID: 19922872
Thomas T, Dixon MP, Kueh AJ, Voss AK. Mof (MYST1, KAT8) is essential for progression of embryonic development past the blastocyst stage and required for normal chromatin architecture. Mol Cell Biol. 2008 Jun 9 PMID: 18541669