skip to primary navigationskip to content
 

Tony Kouzarides

kouzaridesTony Kouzarides PhD FRS FMedSci, Professor of Cancer Biology, Member of the Department of Pathology.

Kouzarides Group website | Europe PMC | Pubmed

 

 

 

 

Epigenetic modifications and cancer

2016 KouzaridesDo chromatin and RNA modifications offer therapeutic targets? DNA exists in the cell nucleus wrapped around histone proteins to form chromatin, a structure that must be navigated by the transcriptional machinery in order to ‘read’ the genetic code. 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 DNA, RNA and histone modifications. We try to understand the cellular processes they regulate, their mechanism of action and their involvement in cancer.

We recently identified a novel modification of histones, methylation of glutamine, and showed that it regulates transcription; a different histone modification, citrullination, was shown to have a role in pluripotency; a novel RNA methyltransferase (BCDIN3D) was shown to be involved in cancer; and a small-molecule epigenetic inhibitor, I-BET, was shown to displace BET proteins from leukaemia genes and to be effective against MLL-leukaemia. I-BET is currently in clinical trials. 

Selected publications:

• Gilan O et al. (2016) Functional interdependence of BRD4 and DOT1L in MLL leukemia. Nat Struct Mol Biol. 2016 Jun 13. doi: 10.1038/nsmb.3249. [Epub ahead of print]

• Picaud S et al. (2015) Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy. Cancer Res. 75(23):5106-19.

• Viré E et al. (2014) The breast cancer oncogene EMSY represses transcription of antimetastatic microRNA miR-31. Mol Cell. 53(5):806-18.

• 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

groupKouzarides2015

Video: Meet Tony Kouzarides

Plain English

The cells in our body all contain the same DNA, but different parts of that DNA are expressed in order to create different types of cells. There are a number of ways in which gene expression is regulated; one of these is through attachment of small chemical groups at specific locations on the DNA molecule, that may help or hinder gene expression. In addition, because the DNA molecule is wrapped around histone proteins in a structure called chromatin, which interacts with some types of RNA molecules, similar chemical modifications of either histones or non-coding RNA can also affect which parts of the DNA will be expressed. Enzymes that add or remove these chemical groups to DNA, RNA and chromatin have been identified in cells, and we are studying those modifying enzymes to find which ones might be related to disease processes, in particular to cancer.

Co-workers

Andrej Alendar • Paulo Amaral • Andrew Bannister • Isaia Barbieri • Ester Cannizzaro • Ka Hing Che • Alistair Cook • Namshik Han • Sri Lestari • Nikki Mann • Carlos Melo • Valentina Migliori • Gonzalo Millan Zambrano • Rebecca Nunn • Luca Pandolfini • Sam Robson • Helena Santos Rosa • Meike Wiese