Nutritional Sciences Investigator Wins NIH Challenge Grant

Kirsten Limesand
Kirsten Limesand

By Jeff Harrison, University Communications

Each year approximately 40,000 people in the U.S. are diagnosed with some form of head and neck cancer. The majority of those patients will have surgery to remove the tumors, followed by one or more rounds of radiation therapy to kill any lingering cancer cells.

A common side effect of radiation to this area is damage to the adjacent, normal salivary glands. Patients commonly experience a dry mouth that can lead to oral sores and infections, cavities, difficulty chewing and swallowing food and loss of taste.

Kirsten Limesand, an assistant professor of nutritional sciences in the University of Arizona College of Agriculture and Life Sciences, has received a two-year NIH Challenge Grant worth nearly $1 million to study this problem. Specifically, Limesand is examining the role of autophagy in salivary glands in response to radiation therapy.

Autophagy is an ongoing process where cells digest and recycle their proteins and organelles. This helps starving cells break down and redirect components from non-essential to essential cell functions. The process and the mechanics behind it are not well understood, but autophagy appears to have some role in preventing and fighting disease and infection. It also, in some cases, could make those problems worse.

Side effects from radiation therapy begin within a few days and can continue for one to two years. Because saliva is essential for maintaining oral health, salivary gland damage can greatly decrease a person's quality of life. Despite a volume of knowledge about salivary glands, there is no good way permanently to restore gland function. While artificial saliva is available, clinicians generally don't regard it as a good long-term solution.

Limesand and her research team will use compounds designed to activate or inhibit autophagy to determine whether it protects salivary glands or increases their injury. She said this initial research should offer answers about restoration. Ultimately, the team's goal is to discover how to speed the healing process in salivary glands.

"The therapeutic interventions we are testing, if successful, could restore salivary gland function in thousands of head and neck cancer patients who have completed anti-cancer therapies yet continue to suffer from the side effect of salivary gland hypofunction," Limesand said.

NIH's challenge grants are designed to fund highly innovative research that offers the potential for great impact. Of the thousands of proposals submitted, less than 3 percent received funding.

Limesand's collaborators include Professor David Ann in the department of clinical and molecular pharmacology at Beckman Research Institute of City of Hope in Los Angeles, and Randy Burd in the UA department of nutritional sciences.