UArizona Health Sciences Researcher to Study Cellular Stress Responses Common in Cancer, Aging

Wednesday, August 26, 2020

Bolstered by a recent $1.6 million federal grant, Dr. Timothy Bolger, a scientist at the University of Arizona Cancer Center, is investigating how cells respond to stress and the role this process may have in cancer growth and aging.

Understanding how cells respond to stress may provide new building blocks for designing future cancer and aging treatments, and a University of Arizona Health Sciences researcher has received a five-year, $1.6 million grant from the National Institute of General Medical Sciences to further study these implications.
Leading the research is Timothy Bolger, PhD, a research member in the UArizona Cancer Center’s Cancer Biology Program and assistant professor in the Department of Molecular and Cellular Biology at the UArizona College of Science. His lab focuses on how the critical process of protein synthesis (how proteins are made) is altered when facing adverse conditions, such as a lack of oxygen or nutrients. This is known as cellular stress. When this process is not properly regulated, cancer cells can promote their own growth and survival in tumors.
Dr. Bolger and colleagues wrote about these mechanisms in a paper published a year ago in the journal Molecular Biology of the Cell, or MBoC.
“If a lack of nutrients exists, the protein synthesis response should make enzymes that can make more of the missing nutrient,” he said. “Or if little oxygen is present, that can alter the rates at which the cell uses energy and molecules until normal levels are restored. Sometimes this does not occur, however, and it can have implications for cancer and aging.”
Dr. Bolger’s research will utilize yeast models to examine a protein called Ded1, also known as DEAD-box helicase 3 X-linked or DDX3X, in humans. This particular enzyme (a protein that speeds up chemical reactions in the body) is known to act differently under cellular stress, Dr. Bolger said. He wants to study the activity occurring around this enzyme – along a molecular pathway – that causes it to function differently during the protein synthesis response, potentially leading to cancer growth.
Mutations to the DDX3X protein have been linked to several cancers, especially medulloblastoma, a fast-growing form of cancer that occurs in the lower, back part of the brain, known as the cerebellum. Medulloblastoma, which commonly affects children and young adults, is the most common type of cancerous brain tumor in children, with 250 to 500 cases diagnosed per year – more than 70% in children younger than age 10. Dr. Bolger seeks to determine if those mutations may have an effect on the stress response in the cancer cells.
“This is a very fundamental research project right now,” Dr. Bolger said. “But if we understand stress responses, then that may tell us something about how cancer cells are bypassing these stress responses. The knowledge gained could be used in future projects to design therapeutics for those diseases.”
Dr. Bolger’s research also investigates the connection between stress response pathways and aging, since the ability to produce a robust cellular stress response has been linked to human longevity.
National Institute of General Medical Sciences, a unit of the National Institutes of Health, under Award No. 1R01GM136827-01.