Metabolism is not the only link to cancer being explored at Princeton. Many researchers across genomics, chemistry, molecular biology, computer science and other departments are looking for ways to understand and kill tumors. Tom Muir, the Van Zandt Williams Jr. Class of 1965 Professor of Chemistry, leads a project to explore cancer-associated mutations in proteins called histones, around which DNA strands coil to form a space-saving structure called chromatin.

A study published by his group in Nature Chemical Biology in 2021 found that histone mutations may contribute to the development or progression of a wide range of human cancers.

The research builds on a paper published in collaboration with the team of David Allis of The Rockefeller University in 2020 in Nature. “We noticed, based on previous work, that a lot of different mutations in histones were associated with different cancers — and to different degrees,” said Michelle Mitchener, one of the study’s lead authors and a Princeton postdoctoral research fellow. The previous work, which focused on data mining, provided an overview of where the mutations are located in chromatin, as well as hypotheses about their roles.

The Muir team “focused on trying to figure out functionally and biochemically what those mutations are actually doing,” she said. “If they contribute to cancer, then how? Can we figure out, at a structural and biochemical level, what they’re doing?”

With funding from the National Institutes of Health, researchers looked at mutations within the cores of the histones themselves to see if and how they might be impacting disease states.

“We think that mutations that affect chromatin remodeling can contribute to disease and cancers in humans,” said John Bagert, the co-lead author on the paper and an associate research scholar.

“We’ve identified the sites and the mutations at those sites that we think are causing problems.”

This article was originally published with "Cancer connection: Researchers collaborate on the roles of diet, metabolism and medicines in the fight against cancer" in Discovery: Research at Princeton Magazine.