Editor’s note: This week’s Deep Dive feature focuses on human enzyme research.

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RESEARCH TRIANGLE PARK – It’s the biggest National Institutes of Health grant in Appalachian State University’s history, but to Michael Reddish, Ph.D., the researcher responsible for pulling in $1.6 million in funding, it’s one step in a lengthy process.

Reddish, an assistant professor in App State’s Department of Chemistry and Fermentation Sciences, is researching human enzymes in an effort that could lead to new therapies for treating cancer and other serious diseases. He doesn’t have a Eureka moment in the lab when he knew he had a grant-worthy discovery.

Instead, he takes the long view when it comes to his specialty – how enzymes work. Specifically, human cytochrome P450 enzymes, which are proteins that help the body metabolize drugs and other substances.

“The P450 enzyme community is very large,” Reddish said. “Researchers can go at it from a number of different directions. When I started talking to colleagues across the country about what I was doing, they found it pretty interesting.”

Michael Reddish, Ph.D. (Photo by Chase Reynolds, App State)

Early Support from NCBiotech

Reddish relies on a network of peers, mentors, students and grantmaking organizations to propel his research. The NIH grant, just announced, is a milestone in the study of the P450 27 family of enzymes. Reddish is investigating how these enzymes function, as alterations in the P450 27 family caused by medical therapies can either help or harm the patient.

One critical moment that stands out to Reddish is a $20,000 Flash Grant from the North Carolina Biotechnology Center he received in 2021. The grant helped jump-start research into an aggressive form of breast cancer, giving his lab the funds necessary to test promising ideas.

While the effort didn’t pay off with a key discovery, it led to additional areas of research that resulted in the NIH grant.

“P450 enzymes have a lot of broad applications,” he said. “With the Flash Grant, our approach was to pretty quickly evaluate whether current FDA-approved drugs could be targeted for breast cancer treatment. We learned that what we expected to happen wasn’t the way it worked out. But that allowed us to expand and pivot into the work we’re doing now, which has applications in many areas.

“I don’t think we would have been successful with these major grants if not for the support of NCBiotech,” he said.

Susan Lankford, Ph.D., NCBiotech’s director of science and technology development, said Reddish’s P450 enzymes research is a prime example of the purpose of the Flash Grant program.

“Researchers often have ideas in the early stages that need further investigation, but without resources, they can’t immediately pursue them,” she said. “The goal is to test the potential of these ideas and advance them to another phase.”

Key Role for Students

With support from NIH and the NCBiotech Flash Grant, as well as a $250,000 National Science Foundation grant, Reddish is well on his way to a better understanding of how P450 enzymes function.

It’s still early in the process. But since alterations in the P450 27 family can contribute to the formation of some cancers, his research might help unlock important clues to developing new medications or modifying existing ones.

When Reddish is in the lab, he’s not surrounded by other Ph.D. researchers or doctoral candidates. His team is made up of App State undergraduate students getting hands-on experience in complex areas of research.

“Our department has a great culture of supporting undergrads,” he said. “The bulk of the work is in their hands, working with proteins, running high-end instrumentation. The students are running all the equipment.”

To Jonathan Snover, Ph.D., executive director of NCBiotech’s Western Office, the work of Reddish’s lab illustrates how high-quality research is happening across the state’s universities and is an important aspect of training future scientists.

“I applaud the efforts of Dr. Reddish, more so because such achievements are astonishing in a research lab without doctorate-level students,” he said. “App State is one of our many universities where this level of advanced research can take place. Dr. Reddish and his students are leading the way toward important discoveries and showing what’s possible in North Carolina.”

(C) N.C. Biotech Writer