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Themes / Divisions

About

The aim of our 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.

Publications

Selected publications from Prof Tim Thomas

Bergamasco MI, Ranathunga N, Abeysekera W, Li-Wai-Suen CSN, Garnham AL, Willis SN, McRae HM, Yang Y, D’Amico A, Di Rago L, Wilcox S, Nutt SL, Alexander WS, Smyth GK, Voss AK, Thomas T. The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function. Stem Cell Reports. 2024;19(4):10.1016/j.stemcr.2024.02.005

Bergamasco MI, Vanyai HK, Garnham AL, Geoghegan ND, Vogel AP, Eccles S, Rogers KL, Smyth GK, Blewitt ME, Hannan AJ, Thomas T, Voss AK. Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice. Journal of Clinical Investigation. 2024;134(7):10.1172/jci167672

Rasool D, Burban A, Sharanek A, Madrigal A, Hu J, Yan K, Qu D, Voss AK, Slack RS, Thomas T, Bonni A, Picketts DJ, Soleimani VD, Najafabadi HS, Jahani-Asl A. PHF6-mediated transcriptional control of NSC via Ephrin receptors is impaired in the intellectual disability syndrome BFLS. EMBO Reports. 2024;25(3):10.1038/s44319-024-00082-0

Mah SYY, Vanyai HK, Li-Wai-Suen CSN, Garnham AL, Wynn J, Bergamasco MI, Malelang S, Wilcox S, Biben C, Smyth GK, Thomas T, Voss AK. ING4 and ING5 are essential for histone H3 lysine 14 acetylation and epicardial cell lineage development.Development. 2024;151(5):10.1242/dev.202617

Sharma S, Chung C-Y, Uryu S, Petrovic J, Cao J, Rickard A, Nady N, Greasley S, Johnson E, Brodsky O, Khan S, Wang H, Wang Z, Zhang Y, Tsaparikos K, Chen L, Mazurek A, Lapek J, Kung P-P, Sutton S, Richardson PF, Greenwald EC, Yamazaki S, Jones R, Maegley KA, Bingham P, Lam H, Stupple AE, Kamal A, Chueh A, Cuzzupe A, Morrow BJ, Ren B, Carrasco-Pozo C, Tan CW, Bhuva DD, Allan E, Surgenor E, Vaillant F, Pehlivanoglu H, Falk H, Whittle JR, Newman J, Cursons J, Doherty JP, White KL, MacPherson L, Devlin M, Dennis ML, Hattarki MK, De Silva M, Camerino MA, Butler MS, Dolezal O, Pilling P, Foitzik R, Stupple PA, Lagiakos HR, Walker SR, Hediyeh-Zadeh S, Nuttall S, Spall SK, Charman SA, Connor T, Peat TS, Avery VM, Bozikis YE, Yang Y, Zhang M, Monahan BJ, Voss AK, Thomas T, Street IP, Dawson S-J, Dawson MA, Lindeman GJ, Davis MJ, Visvader JE, Paul TA. Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer. Cell Chemical Biology. 2023;30(10):10.1016/j.chembiol.2023.07.005

Dahlin JL, Hua BK, Zucconi BE, Nelson SD, Singh S, Carpenter AE, Shrimp JH, Lima-Fernandes E, Wawer MJ, Chung LPW, Agrawal A, O’Reilly M, Barsyte-Lovejoy D, Szewczyk M, Li F, Lak P, Cuellar M, Cole PA, Meier JL, Thomas T, Baell JB, Brown PJ, Walters MA, Clemons PA, Schreiber SL, Wagner BK. Reference compounds for characterizing cellular injury in high-content cellular morphology assays. Nature Communications. 2023;14(1):10.1038/s41467-023-36829-x

Croft B, Bird AD, Ono M, Eggers S, Bagheri‐Fam S, Ryan JM, Reyes AP, van den Bergen J, Baxendale A, Thompson EM, Kueh AJ, Stanton P, Thomas T, Sinclair AH, Harley VR. FGF9 variant in 46,XY DSD patient suggests a role for dimerization in sex determination. Clinical Genetics. 2023;103(3):10.1111/cge.14261

Kueh AJ, Bergamasco MI, Quaglieri A, Phipson B, Li-Wai-Suen CSN, Lönnstedt IM, Hu Y, Feng Z-P, Woodruff C, May RE, Wilcox S, Garnham AL, Snyder MP, Smyth GK, Speed TP, Thomas T, Voss AK. Stem cell plasticity, acetylation of H3K14, and de novo gene activation rely on KAT7. Cell Reports. 2023;42(1):10.1016/j.celrep.2022.111980

Mah SYY, Vanyai HK, Yang Y, Voss AK, Thomas T. The chromatin reader protein ING5 is required for normal hematopoietic cell numbers in the fetal liver. Frontiers in Immunology. 2023;14:10.3389/fimmu.2023.1119750

Wichmann J, Pitt C, Eccles S, Garnham AL, Li-Wai-Suen CSN, May R, Allan E, Wilcox S, Herold MJ, Smyth GK, Monahan BJ, Thomas T, Voss AK. Loss of TIP60 (KAT5) abolishes H2AZ lysine 7 acetylation and causes p53, INK4A, and ARF-independent cell cycle arrest. Cell Death & Disease. 2022;13(7):10.1038/s41419-022-05055-6

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