The germ of the idea came to neurosurgeon Behnam Badie, M.D., over a meal with diabetes expert Samuel Rahbar, M.D., Ph.D. “We would meet for lunch and I would ask about his career and research,” Badie said. “I learned a lot during those talks, especially about his discovery of hemoglobin A1c.” Hemoglobin A1c is a form of hemoglobin that has the sugar glucose attached to it.
“It is the standard risk measurement for complications in people with diabetes,” explained Badie, chief of the Division of Neurosurgery and director of the Brain Tumor Program.
|Behnam Badie (Photo by Walter Urie)|
Why would a neurosurgeon expert find diabetes research so fascinating? Badie realized it might have implications for his own patients.
Their discussions delved deeper into diabetes research by Rahbar, professor in the Division of Diabetes, Endocrinology & Metabolism, branching into what are called advanced glycation end products (AGEs). AGEs form when excess sugar binds to proteins and lipids in the bodies of people with diabetes.
When AGEs connect with receptors for advance glycation end products (RAGE), 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.
RAGE also happens to be active around gliomas.
That realization brought puzzle pieces together for Badie, who began researching RAGE. He found the receptors appear to help fool the immune system into ignoring these brain cancers.
“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 James S. McDonnell Foundation recognized the potential of Badie’s work. It recently granted Badie a 21st Century Science Initiative in Brain Cancer Research Award to study the role RAGE may hold in treating brain tumors.
The three-year, $450,000 grant supports Badie’s collaborative study with colleague Rama Natarajan, Ph.D., professor in the Department of Diabetes, Endocrinology & Metabolism, to better understand how RAGE suppresses 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.”
The research team will investigate how turning off RAGE affects the activation and function of macrophages in brain tumors. The team also will examine RAGE’s role 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.”