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 is the molecule that carries oxygen in red blood cells. Hemoglobin A1c is a special type of hemoglobin that has a form of sugar 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.
Why would a neurosurgeon find diabetes research so fascinating? Because it might have implications for Badie’s own patients.
Neurosurgeon and brain cancer researcher Benham Badie in the operating room. (©2005 Philip Channing)
Their talks delved deeper into molecules studied by Rahbar, professor in the Department of Diabetes and Metabolic Diseases Research. These substances are called advanced glycation end products (AGEs).
In people with diabetes, too much sugar circulates and accumulates in the blood. AGEs form when this extra sugar binds to proteins and other molecules in the body.
These AGEs lie behind a lot of the complications of diabetes. AGEs can connect with receptors for advance glycation end products, or RAGE, much like a key fitting into a lock. This connection triggers inflammation and leads to conditions such as the deadening of nerve sensation and vision loss.
When other molecules activate RAGE, it can lead to other serious health conditions such as the narrowing of arteries, congestive heart failure and Alzheimer’s disease.
And, as it turns out, RAGE happens to be active around glioma, a brain cancer.
That realization brought puzzle pieces together for Badie. He began researching RAGE and found the receptors appear to help fool the immune system into ignoring glioma.
His preliminary studies suggest that RAGE might help stifle cancer-fighting cells around brain tumors by activating STAT3, a protein that seems to promote cancer growth and suppress the immune system. Called macrophages, these special cells are 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,” Badie said.
Badie is collaborating with colleague Rama Natarajan, Ph.D., professor in the Department of Diabetes and Metabolic Diseases Research, to better understand how RAGE suppresses the immune response.
Natarajan has conducted extensive research into AGEs and RAGE for diabetes.
Their research could lead to the development of new treatments designed to reboot a patient’s immune system to battle a brain tumor.
“Brain tumors are often very difficult to treat due to their location in sensitive brain tissue,” said Badie. “It’s vital that we develop new treatments that are both safe and effective for use against brain tumors.”