With support from the National Institutes of Health 2026 High Risk, High Reward New Innovator Awards, University of Wisconsin–Madison biochemistry professor Monica Neugebauer is exploring nickel-dependent enzymes that can drive new-to-nature chemical reactions.
Neugebauer’s lab focuses on discovering and engineering metalloenzymes — enzymes that contain a metal — and harnessing their power. By helping to speed up chemical reactions, her group’s work creates new possibilities for building complex molecules and expanding the scope of the field of synthetic chemistry.
“Many drug molecules are very structurally complex,” says Neugebauer. “Enzymes are amazing because they can perform chemistry on complex molecules with high precision, allowing us to tune their therapeutic properties.”
While metals such as palladium and platinum have found uses in catalyzing reactions to make therapeutic drugs, enzymes that harness nickel, which is more abundant and less costly, could provide alternative strategies for drug synthesis. However, few nickel-dependent enzymes have been discovered, limiting nickel’s possibilities for biomedical use.
“We just don’t have many nickel enzymes that we can even use as starting points for exploring what kinds of reactions they can do,” says Neugebauer. “The fact that there are so few known nickel enzymes makes it especially exciting to explore.”
While her lab searches for existing nickel enzymes using bioinformatics techniques, they also will explore whether non-nickel enzymes can be modified to use nickel. Neugebauer will also be testing new enzymes’ selectivity in catalyzing biochemical reactions, a first step in identifying new drug synthesis options.
“I’m grateful to have the opportunity to do this kind of research. This grant differs from many traditional funds and grants because it allows us to take risks, and trying to find something new is always a risk,” says Neugebauer. “This grant is a testament to the hard work that my lab group has done to produce preliminary data showing the potential for our pipeline to yield new discoveries. I’m really proud of them and I’m excited to see what we discover.”
Neugebauer is among 58 researchers receiving New Innovator Awards this year. The awards, created to support unconventional approaches to major challenges in biomedical and behavioral research, total approximately $237.5 million to be distributed over as many as five years for unusually innovative research done by early-career investigators.
Read more about the New Innovator Awards on the NIH website.
Written by Renata Solan.