Dr. Peter Jones shares his perspective on the latest excitement in epigenetics research and the future potential of epigenetic therapies.
Epigenetics and Improved Therapies for Cancer
The whole field of epigenetics has taken off and I think the development of epigenomics the idea that you could look at the entire epigenome of a human cell is very exciting, we couldn’t do that before; everything was based upon a one gene at a time type of approach. And so I didn’t want to miss out on the fun quite frankly.
My lab is interested in several things at the moment. Firstly we’re interested in how epigenetic processes interact with each other, trying to get a much more holistic view of how the different components of the nucleus work together to set up stable states of gene expression. You know most of our focus up to now has been in the area of DNA methylation. But clearly DNA methylation and nucleosome remodelers and histone modifications actually talk to each other; so we’re interested in how these things talk to each other. And specifically what we want to know is; how is this relevant to normal differentiation and how is it relevant to cancer formation? So we’re very much a cancer lab, interested in how epigenetics alters the phenol type of a cell to make it a cancer cell.
The other half of the lab is really focused on epigenetic therapies; we’re trying to understand at a very basic level how drugs which are now used in the clinic reorganize the epigenome to switch genes on because we want to make better drugs in the future and hopefully be able to treat patients better.
The Next Frontiers
So the frontiers in the fields of epigenetics and epigenomics are going to be really I think mapping whole human epigenomes. So you know I’ve played a role in the development of the International Human Epigenome Consortium (IHEC) which now has 8 countries signed on; and we plan on mapping 1,000 human epigenomes. And so I think it’s going to be very, very important to do that to get what’s a map of the ground state of different cell types and to have a series of marks and maps that people can rely on. So that’s a very exciting thing, that’s starting right now. The next thing is gonna be I think is going to be the transitioning from the field of cancer into other human diseases. Particularly chronic diseases, such as diabetes, maybe obesity, mental health; these are areas in which there is a strong feeling that they may be an epigenetic basis to the disease.
And then the third thing I think will be in the development of epigenetic therapies which is my own personal love; the idea that we can actually modify epigenomes and treat cancer patients in particular and actually have an impact on these disease states. So it’s going to be a very exciting 5 or 10 years.
So what will the perfect epigenetic therapy look like? Well first of all it will have an impact, we hope will increase the survivability of patients. I think that we will have much more selective drugs, at the moment, at least for the DNA methylation inhibitors or PAN inhibitors it’s quite possible we will develop inhibitors for different DNA methyltransferase enzymes for example. I think the idea of coupling treatments together, like using histone methyltransferase inhibitors at the same time as a DNA methylation inhibitor.
And finally what’s really important I think will be the transitioning from the therapies, which now only approved for the use in liquid tumors, into solid cancers. So working together with Steve Balin with our Stand Up to Cancer, Epigenetics Dream Team we’re actually really trying to bring these therapies into the treatment of solid cancers and do it much earlier. At the moment what happens, we can only treat patients after they’ve been through the many other courses of treatment and I think if we can get the therapy in at the beginning, because we think epigenetics miscues occur at the beginning of the cancer, I think we’ll have much more success in helping people.
The advance that changed everything was next generation sequencing, the fact that one could sequence DNA very very rapidly, and so that didn’t become the rate limiting step. I think that coupled with the development of chromatin immuno-precipitation has really allowed us to do these experiments much more rapidly than we could ever imagine in the past. So the next generation sequencing (chip seq ) has really changed everything. At the same time from the point of view of the DNA methylation analysis the idea that one could take bisulfite sequencing and look at the distribution of all of the methyl groups from DNA; and that’s been done now not only in plants but animals. That’s really a major breakthrough.