About the TK Lab

Our interest, for many years, has been the characterization of the pathways leading to epigenetic modifications of Histones and their involvement in cancer. More recently, our focus has moved towards the characterization of epigenetic modifications of RNA, once again in the context of cancer. For review see: Barbieri & Kouzarides, Nat. Rev. Cancer, 2020.

The RNA modification field is very underexplored. Over 140 modifications have been identified on RNA, but most of these have been described on tRNA and rRNA. Only a few have been identified on mRNA and ncRNA, because these are much less abundant and more complex. We believe many more unidentified modifications exist on mRNA and ncRNA, so our lab is focusing on uncovering these. We have now developed sensitive assays to detect them, using antibodies, mass-spectrometry and chemical reactions, and nanopore sequencing. Using these assays we can now detect many new modifications on mRNA and ncRNA, some of which we have characterized with respect to their mechanism of action (Pandolfini et al, Mol. Cell, 2019).

The reason we got into this RNA modification field, is because we identified a protein, BCDIN3D, which can methylate RNA, and can alter the metastatic characteristics of cancer cells (Xhemalce et al, Cell, 2012). This was, at the time, the first evidence that an RNA methyltransferase could be implicated in cancer. Since then we have identified many RNA enzymes involved in AML-leukaemia (through CRISPR screens), which we are now investigating for their cancer mechanism. Interrogation of one of these enzymes, METTL3, has revealed a new chromatin-based pathway for leukaemia, where the METTL3 enzyme is recruited to specific leukaemia genes via transcription factor CEBP-Z (Barbieri et al, Nature, 2017).

We are committed to targeting epigenetic pathways for the treatment of cancer. We have already done this for BRD4 ( a reader of histone acetylation) via a collaboration with GSK (Dawson et al, Nature, 2011). To interrogate the possibility of targeting RNA modifying enzymes for cancer, we have set up a biotech company, STORM Therapeutics, whose goal is to target enzymes that modify RNA with small molecules. Our lab has very close links with STORM, through a framework agreement with the University of Cambridge that allows free flow of information. We therefore have joint lab meetings and research collaborations with STORM, which lead to joint publications. STORM has developed new inhibitors, which we are currently analysing for their efficacy and mechanism of action in the lab. One of these inhibitors is expected to be in clinical trials in 2021. This will be the first small molecule against an RNA modifying enzyme to do so.

How the lab works:

The lab has space for a maximum of 15 people. There are, in general, many more postdoctoral researchers than PhD students. We have our own bioinformatician (at least one) as well as technical staff. We also have Tony’s Personal Assistant, the awesome Nikki Mann, who is in total control of everything!

Research in the lab is funded primarily by a Cancer Research UK Programme Grant. Salaries for researchers come from grants belonging to the lab, or from fellowships belonging to individual researchers. Core equipment and facilities are funded by Wellcome Trust and CRUK grants held by the Gurdon Institute.

The TK Lab is multinational. We have had researchers from 25 different countries. The vast majority of PhD students and postdoctoral research stayed in academia after leaving the lab. Our lab statistics  show that 82% of people leaving the lab have stayed in academia .

– To find out more information on all of our alumni, please visit our Lab Statistics page.
– To find out where they all went, you can explore our Alumni Map.

Lab Retreat:

The TK Lab has an annual retreat, where we discuss new strategies, new directions, and new techniques. Retreats are usually overseas, within Europe, and last for 4 days. In recent years we have been to Ibiza, (Spain), Sicily (Italy), Prague (Czech Republic). We have visited over 21 places in Europe so far, including Rimini, Amsterdam, Lisbon, Barcelona, Macon, Seville, Rome, Berlin, Brussels, Lille, Porto, Salobrena, Turin, Krakow, Prague, Sicily, and Ibiza.

The Other Lab:

The lab runs on the principle of “Work hard, play hard”. This principle has been taken to another level, with Tony’s acquisition of a Cocktail bar in Cambridge. The bar is named “The Lab” and it is few minutes walk from the lab. So no excuses for leaving the lab while you are in Cambridge! You can find out more about this, and other TK projects here.