DUARTE, Calif., November 17, 2008 — The James S. McDonnell Foundation awarded a research grant to Behnam Badie, M.D., director of City of Hope’s Brain Tumor Program, to study the role a gene receptor linked to complications from diabetes may play in treating brain tumors. The 3-year, $450,000 21st Century Science Initiative in Brain Cancer Research Award supports Badie’s collaborative study with City of Hope colleague Rama Natarajan, Ph.D., professor in the Department of Diabetes, Endocrinology & Metabolism, to better understand the gene receptor’s role in suppressing the immune response. This research may one day lead to the development of new treatments designed to reboot a patient’s immune system to battle a brain tumor.
“I am grateful to the McDonnell Foundation for their support of this unexplored avenue of research,” said Badie, lead investigator of the study. “Brain tumors are often very difficult to treat due to their location in sensitive brain tissue. It’s vital that we develop new treatments that are both safe and effective for use against brain tumors.”
In people with diabetes, excess sugar binds to proteins and fats in a process known as glycation that leads to the creation of an excess amount of molecules known as advanced glycation end products (AGEs). When AGEs connect with receptors for advance glycation end products (RAGEs) they signal the body to produce molecules that cause inflammation and lead to conditions such as the deadening of nerve sensation and vision loss. When RAGE expression is activated by other molecules, it can lead to other serious health conditions such as the narrowing of arteries, congestive heart failure and Alzheimer’s disease.
“Our preliminary studies suggest that RAGE may play a role in suppressing macrophage function around brain tumors through the activation of STAT3, a protein that has been shown to promote cancer growth and suppress the immune system,” said Badie. “Macrophages are commonly considered the main immune cell in the brain. If we are able to block RAGE, it may be possible that we can get macrophages to function normally and attack brain tumor cells.”
The research team will investigate how turning off RAGE affects the activation and function of macrophages in brain tumors. They will also examine the role RAGE has in controlling the expression of STAT3 proteins. Studies of STAT3 by City of Hope researchers have firmly established the protein’s role in promoting tumor growth and suppression of immune response in a variety of cancers. Natarajan has conducted extensive research into AGE and RAGE for diabetes.
“It is interesting to learn more about the unique role RAGE may play in brain tumors,” said Natarajan. “City of Hope’s commitment to sharing ideas and collaboration across different medical practices opens doors to different perspectives and new avenues of research one might not have considered before.”
About the James S. McDonnell Foundation
Founded in 1950 by the late aerospace pioneer and founder of what would become the McDonnell Douglas Corporation, James S. McDonnell's belief that science and technology gives mankind the power to shape knowledge for the future while improving our lives. "Mr. Mac's" vision continues to be realized through the research these grants are supporting. Since the inception of the 21st Century Science Initiative in 2000, more than $123 million in funding has been awarded.