By Lara Ivanitch

Asher Utz compares his field of study, biochemistry, and its use in cancer research to solving a puzzle.

“Although it can be challenging work, the pieces come together with perseverance,” Utz says.

And when the doctoral candidate explains the research he does at NC State University in layman’s terms, he describes post-translational modification as a process of adding “little hats” to an enzyme. There’s something fun about the way Utz refers to his work; it’s clear how much he enjoys it.

Utz almost missed out on the chemistry aspect of his studies. He began as a biology major at the University of Mary Washington and had an opportunity to work in an undergraduate lab. There was one catch — Utz had to switch his degree tobiochemistry to get the job. He made the change and didn’t look back. He appreciates that “biochemistry encourages you to dive deeper into the actual cellular decisions that are happening to cause an outcome.”

When looking into graduate schools, Utz knew he wanted to continue researching cancer. In addition to having the desire to contribute to knowledge about a disease that has touched his family, Utz finds the mechanisms behind cancer fascinating.

“It’s just a mistake your body is making, but it’s so devastating,” he says.

Utz conducts his research under the supervision of Melanie Simpson, head of the Department of Molecular and Structural Biochemistry at NC State and director of research for the Integrative Sciences Initiative. Utz’s doctoral work focuses on the role of the enzyme UDP-glucose dehydrogenase (UGDH) in prostate cancer. Overproduction of the enzyme is associated with many cancers, although the enzyme is also essential for life.

“Patients who lack UGDH activity during development experience a devastating disorder known as Jamuar syndrome, or UGDH-related disorder,” he notes.

Utz’s thesis work, recently published in Matrix Biology, focuses on restoring healthy activity of UGDH in prostate cancer. “With UGDH, everything has to be kept in a fine balance. It’s like a Goldilocks phenomenon, where you can’t have too much or too little activity — it must be just right.”

To address the imbalance, the Simpson Lab team examined post-translational modification of the enzyme. This is where the little hats come in.

“These hats regulate its activity or where UGDH goes in the cell and how its product is utilized,” Utz says.

However, phosphorylation, the scientific term for the event that “adds hats” to the enzyme, sometimes goes awry. “This causes UGDH to direct its product towards pathways that support biosynthesis and growth and these huge tumoroids that form,” Utz explains.

The Simpson Lab is the first to report this modification to UGDH, and is currently working to understand the cellular “decisions” that come before and after it. This new knowledge could eventually lead to different clinical approaches that prevent treatment-resistant prostate cancer.

“It’s potentially identified a novel, or brand new, target for therapeutics — specifically targeting this phosphorylation event in the enzyme,” Utz says.

The recipient of this year’s Anne A.J. Work Award for outstanding biochemistry graduate research, Utz hopes to run his own lab in the future. For now, he continues to learn and contribute to the Simpson Lab. He appreciates the variety of techniques and protocols he has been exposed to through this research.

“We’re not limited in the questions we can ask, and the biochemistry department is very collaborative and supportive.”

This post was originally published in College of Agriculture and Life Sciences News.