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Michael Stitzel: Epigenome in Type 2 Diabetes

Michael Stitzel: Epigenome in Type 2 Diabetes
Assistant professor, The Jackson Laboratory
Recommended by Francis Collins, National Institutes of Health

Stitzel.jpgMichael Stitzel joked that his research has led him to climb up the evolutionary tree. As an undergraduate he worked with yeast, and over the years, he has worked his way up to studying Drosophila, C. elegans, and, now, people.

Stitzel shifted from the more basic roots of the tree to the biomedical limbs as a matter of motivation. He said that as a graduate student, though he worked on an important and interesting question, when experiments didn't go well, it was hard for him to get motivated. And so, he found himself drawn to questions with more direct relevance to medicine.

He turned to studying type 2 diabetes. Using a genome-wide association study approach, he identified a number of regions in the genome linked to the disease, but many of them were, as he put it, "in the middle of nowhere." This led him to thinking about epigenetics, and then to later uncover what he and his colleagues dubbed 'stretch enhancers,' longer-than-average enhancers that appear to be driving physiological functions.

"The ability to potentially start identifying regions of the genomes that were different in people who had diabetes and not and the epigenetics just fit in perfectly as a way to initially catalog these places," Stitzel said. "Now I think the sky's the limit with the epigenome."

Stitzel is now setting up his own lab at JAX, where he and his team will be studying the molecular switches they've uncovered in pancreas islet cells as well as how variations in them affect enhancers and chromatin structure. And, he said, there are a number of switches that they have no idea what they do.

"It reminds me a lot of the old house that we bought," he said, adding that "we have switches and when we flip them, we suspect that they will change gene activity, but I have switches in my 1929 old house that I have no idea what the heck they do and what light they are controlling."

Paper of note

In a 2010 Cell Metabolism paper, Stitzel and his colleagues reported on their epigenomic analysis of pancreatic islet cells. By examining DNase I hypersensitive sites, histone H3 lysine methylation modifications, and CCCTC factor binding, Stitzel and his colleagues uncovered some 18,000 putative promoters as well as other regulatory elements.

"[That paper] was trying to define enhancers and regulatory elements in the space, and then I think we got more sophisticated and more systematic in how we did that to allow us to say that the elements that we found in islets were islet-specific and not something that you could find in other cell types," Stitzel said.

That work, he added, set the stage for their work on stretch enhancers, which was published in the Proceedings of the National Academy of Sciences in October.

And the Nobel goes to…

If Stitzel were to win the Nobel Prize, he said he'd like it to be for "having the presence of mind to make an observation and say, 'well, this is interesting or odd,'" and following that up with careful experimentation to understand the phenomenon he observed.

He added that the epigenome could harbor a number of possibilities.

"There is a lot of space in the epigenome, and with variant effects on the epigenome, hopefully there would be something that I would find, an interesting phenomenon, and dig into it," Stitzel said. "But I'm not sure what that would be yet."

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