Can you discuss some of your recent epigenetic studies?

I am very interested in the pluripotent nature of embryonic stem cell features. We take embryonic stem cells and differentiate them into a fibroblast lineage and we use that to interrogate three cell types during that differentiation process. This allows us to capture the key dynamic changes and determine when the differentiation process actually starts.

We started by understanding transcription regulation and then very quickly realized that epigenetic regulation, epigenetic influence, is a very, very important part of it. Cell differentiation has been studied extensively in fields like histone modifications, but no one had been able to look at the DNA methylation at very high resolution in a well-designed system. With the Genome Analyzer we were confident that we could carry out this methylation study quickly and economically. After a few experiments on paper to optimize the experimental design, we determined that we could do this well and at a reasonable, achievable cost. Sample preparation was important, so we spent some time upstream optimizing the bisulfite conversion process. Once that looked good, the sequencing part came very, very straightforward. We were very fortunate to team up with the group at BGI for the informatics part. Their computational capacity and algorithms gave us the processing power to look in every position on the genome at these very interesting methylation patterns. 

With that experience, the goal now is trying to look at more different types of methylation patterns. We're looking at cancer and different tissues, particularly brain tissue. We're also looking at a number of other interesting diseases that have some relevance to DNA methylation.