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Tony Kouzarides

2017 KouzaridesTony Kouzarides PhD FRS FMedSci, Professor of Cancer Biology, Cancer Research UK Gibb Fellow, Director of the Milner Therapeutics Institute, Member of the Department of Pathology.

Kouzarides Group website | Europe PMC | Pubmed

 

  

Epigenetic modifications and cancer

Do chromatin and RNA modifications offer therapeutic targets?

DNA exists in the cell nucleus wrapped around histone proteins to form chromatin. The DNA and histones are decorated with many types of covalent chemical modifications, which can affect transcription and other cellular processes. In addition, non-coding RNAs that regulate chromatin function can be similarly chemically modified.

Our lab is involved in characterising the pathways that mediate and control DNA, RNA and histone modifications. We try to understand the cellular processes they regulate, their mechanism of action and their involvement in cancer. Our recent work on histone modifications has led to the identification of a novel histone phosphorylation site that triggers DNA damage checkpoint recovery.

Our work on RNA identified a novel pathway leading to Acute Myeloid Leukaemia involving an RNA methyltransferase (METTL3), that binds the promoter of leukaemia genes and regulates their translation. Our interest in defining pathways to intervene in cancer has identified an epigenetic small molecule inhibitor, I-BET, that can be effective against Mixed-Lineage Leukaemia, a disease common in children. This potential drug is currently in clinical trials.

Selected publications:

• Barbieri I et al. (2017) Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Nature 552, 126–131.

• Millan-Zambrano G et al. (2018) Phosphorylation of Histone H4T80 Triggers DNA Damage Checkpoint Recovery. Molecular Cell 72, 625–635.

• Christophorou MA et al. (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature 507(7490): 104–108.

• Tessarz P et al. (2014) Glutamine methylation in histone H2A is an RNA- polymerase-I-dedicated modification. Nature 505(7484): 564–568.

• Dawson MA et al. (2011) Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature, 478(7370), 529-533

Kouzarides Group 2017

Video: Meet Tony Kouzarides

Co-workers

Minaam Abbas • Andrej Alendar • Paulo Amaral • Andrew Bannister • Alistair Cook • Eleanor Elgood Hunt • Hannah Kiely-Collins • Marie Klimontova • Tommaso Leonardi • Sri Lestari • Nikki Mann • Carlos Melo • Valentina Migliori • Luca Pandolfini • Helena Santos Rosa • Konstantinos Tzelepis • Daniel Wing