Epigenetics Research at UW-Madison Ready for the Next Step

Staying on the front edge of a fast-growing and rapidly advancing field is never an easy task, but John Denu, leader of the Epigenetics Theme at the Wisconsin Institute for Discovery, is committed to keeping UW-Madison one step ahead of the pack in epigenetics research. A new campus-wide initiative, kicked off in December and centered at WID, looks to the future of chromatin-based gene regulation research in Wisconsin.

Denu's lab in action
Denu’s lab in action.

Epigenetics, a relatively new field of inquiry, is the study of how differing phenotypes — observable characteristics of an organism — can result from a single genome. Researchers study the epigenome, which literally means “on top of the genome,” to understand how particular genes can be turned “on” and “off” and what the consequences of those switches may be. Chromatin, which includes proteins, DNA, and RNA, is the material of most interest to epigenetics researchers. Epigenetics involves a vast array of disciplines, from biology, nutritional science, and medicine to psychology, horticulture, and statistics. Such a wide umbrella offers great opportunities for transdisciplinary breakthroughs, but it can be difficult to focus and unify.

The story of epigenetics research at UW-Madison began in 2008, when John Denu submitted a proposal for a research theme at the nascent Wisconsin Institute for Discovery. The mission was to focus on chromatin structure and function, answering the question of how chromatin regulates gene expression and exploring the molecular, chemical, and physical bases underlying epigenetic mechanisms. The Epigenetics Theme was also intended to serve as a conduit for catalyzing and fostering collaborations around a campus-wide effort including basic, translational, and clinical research.

“The idea was to establish a core group of faculty that could provide an intellectual hub for campus from which we could grow outward,” says Denu, who moved his lab to WID in 2011 and got to work with newly hired epigenetics faculty members Xuehua Zhong, Rupa Sridharan, and Peter Lewis. This team of researchers has helped lay the groundwork for the next chapter of epigenetics research on campus.

The Zhong lab is investigating how DNA methylation regulates epigenetic responses and how these mechanisms are involved in environmental sensing in plants. The Sridharan lab has provided a detailed understanding on how vitamin C and other signaling networks alter the epigenome and facilitate somatic cell re-programming. The Lewis lab continues to perform groundbreaking discoveries on understanding the molecular basis for cancers that originate from mutations in histones.

Denu’s research centers on understanding — and rewriting — the molecular language of epigenetics, connecting the epigenome to metabolism, and understanding how certain proteins are related to transcription, genome maintenance, and diseases of aging. Incorporated in these pursuits are a variety of approaches, including biochemistry, genetics, proteomics, enzymology, and use of mouse models to explore biological function.

“We envisioned this being a stepping stone to something bigger, something campus-wide.”  – John Denu

The Epigenetics Theme is now ready to move into the next phase: outward expansion. In December, Denu called on dozens of faculty from more than ten departments to participate in the launch event for the new campus-wide Epigenetics Initiative. Denu updated his colleagues on the progress made at WID since 2011 before leading discussions about short- and long-term objectives for epigenetics at UW-Madison. Outlined goals included engaging with campus experts, reaching out to clinicians about precision medicine, developing funding mechanisms, managing resources, and communicating about both the needs and accomplishments of epigenetics faculty.

In the short term, Denu hopes to reconvene with his epigenetics colleagues regularly, including a possible spring semester retreat, to gauge progress and push forward. One piece of the puzzle is already in place: a new, unified epigenetics website, epigenetics.wisc.edu. Says Denu, “we envisioned this being a stepping stone to something bigger, something campus-wide.” That vision is beginning to take shape and will position UW-Madison on the cutting edge of the epigenetics research landscape in the coming years.

— Nolan Lendved