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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

2018 Elected International Honorary Member of the American Academy of Arts and Sciences

  

Epigenetic modifications and cancer

Do enzymes that modify chromatin and RNA 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 focus at the moment is modifications of messenger RNA (mRNA) and non-coding RNA. There are very few modifications identified on these low-abundance RNAs, unlike on transfer RNA and ribosomal RNA, where there are many. We have been developing sensitive technologies to detect modifications, such as specific antibodies, chemical reactivity assays and mass spectrometry. Using these, we have been able to detect a number of novel modifications on mRNA and microRNA (short length non-coding RNAs) and have shown that these function to regulate mRNA translation and microRNA processing. Furthermore, we have shown that the enzymes that mediate these modifications are implicated in acute myeloid leukaemia.

Selected publications:

• Pandolfini L et al. (2019) METTL1 promotes let-7 microRNA processing via m7G methylation. Molecular Cell 25 April. DOI: 10.1016/j.molcel.2019.03.040.

• 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 (Nov18 to Feb19)

Video: Meet Tony Kouzarides

Co-workers

Minaam Abbas • Andrej Alendar • Paulo Amaral • Andrew Bannister • Francisco José Campos Laborie • Alistair Cook • Marie Klimontova • Sri Lestari • Nikki Mann • Carlos Melo • Valentina Migliori • Luca Pandolfini • Helena Santos Rosa • Konstantinos Tzelepis • Daniel Wing