Professor Skirmantas Kriaucionis aims to to elucidate the molecular function of DNA modifications in normal cells and cancer. He uses biochemistry and in vivo approaches to investigate the role of DNA modifications in transcription, heritability, mutability and nuclear organisation. Together with advancing knowledge of the basic biology of DNA, his research delineates defects in cancer and aims to target them for therapy.
Although all cells in our body have the same genome, they look different and perform different functions. Epigenetic modifications such as methylations ensure which sets of genes are expressed in specific cells and how this specificity is inherited. Cancer cells show particular epigenetic abnormalities which can be targeted for cancer therapies.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: What is an epigenetic modification?
Skirmantas Kriaucionis: An epigenetic modification is a modification in the genome, which is beyond the DNA sequence. Let me give you an example: we have many cells in our body, they look different and they perform different functions but they have the same genome. How do they do that? They actually express different sets of genes. By express, I mean they use different sets of genes. Some genes are being used in brain cells, others are being used in liver cells. This process must be regulated exactly and precisely. Moreover, when cells divide, for example liver cells, the daughter cells look like their mother cell, and this is the same for many other cell types. Therefore, epigenetic modifications are the modifications which ensure the gene expression profiles, and the heritability of it, when cells divide.
Q: Can you give us an example of an epigenetic modification in cancer?
SK: We know that cancer is a genetic disease: genes get mutated and this causes cancer. Over the last 10 to 20 years, we have noticed that tumours have a lot of epigenetic abnormalities. The genomes are diffferent, and the epigenetic modifications are also very different. One of the most studied epigenetic modifications is one which is localised on the DNA itself; it is a chemical modification called methylation. Methylation can be very different between normal and tumour cells.
Q: Can you tell us about your current research?
SK: We have a number of very interesting projects in the lab. One is to understand how gene expression is being influenced by DNA modifications. We study proteins which are able to bind and modify DNA. We study how gene expression is being regulated. This helps us understand how cancer cells evolve these differences, which can lead to abnormal phenotypes.
A second direction is to understand how these epigenetic alterations affect cancer risks. This is a new direction in which we have invested a lot of time recently and we are hoping to have exciting results very soon.
Q: What are the most important lines of research that have developed over the past 5-10 years?
SK: Some of the most important lines of research are related to technology development. First human genome was sequenced, and now sequencing technologies have developed so rapidly that we can sequence a human genome in days. This opens a lot of interesting opportunities for us. We study epigenetic modifications using the same tools: the same sequencing technologies can be used to study epigenetic modifications as well. Now in a matter of days we can access the whole modification repertoire in normal human cells or in cancer. This very exciting technology opens a lot of different windows for us and we able to use those opportunities to study function of cells and epigenome.
Q: Why does your line of research matter and why should we put money into it?
SK: We study cancer and cancer is a common cause of distress and death in humans. Although we are experts in molecular biology we are always looking for opportunities to discover some targets which could be used for cancer therapy. Therefore, we think it is a good and important direction to go and to invest money in. Science is very unpredictable so we don't know where the most exciting discoveries will come from, but our track record of good research and important discoveries shows we can produce interesting and valuable insights into molecular biology and epigenetics.
Q: How does your research fit into translation medicine within the department?SK: One of our recent projects actually fits it very well. When working on the recycling of epigenetically modified nucleosides, we discovered that cancer cells utilise a slightly different mode of recycling for these epigenetically modified nucleosides. We can use this modes to interfere with cancer growth by killing cancer cells. We are very excited about this direction. We are looking at cancers which have this altered ability to recycle modified bases. One of these cancers is pancreatic cancer, which is a very aggressive and difficult to treat cancer, and we are now strongly interested in pursuing translational opportunities to see whether or not our insights can be used to develop valuable and useful therapies.