Our genes are the blueprints of our lives. They determine how tall we are, whether we have freckles and the color of our hair. They also play a role in our health, influencing whether we are well or sick. Some diseases can be traced to defects in genes, but, enigmatically, not all can. Brothers and sisters with very similar genetic makeups may have vastly different health outcomes at life’s end. Why?
An emerging area of science—epigenetics—offers an answer. In fact, a School of Medicine researcher’s studies may demonstrate that an epigenetic link exists between two of the most common diseases of our time.
Epigenetics is the study of biological processes that switch genes on and off without altering the genetic code itself. Epigenetic changes may be prompted by the environment, diet, stress, aging and other factors.
Of particular interest to Kexin Xu, Ph.D., assistant professor of molecular medicine at UT Health San Antonio, is that epigenetic changes are reversible. That means that some of the world’s most prolific and damaging diseases, such as cancer and diabetes, may not just be halted. The diseases themselves may be reversed.
“By stopping undesirable biological processes that promote cancer, diabetes or both, we can alter the lives of hundreds of thousands of people suffering the effects of these diseases,”
Dr. Xu said. “Epigenetic reprogramming has the potential to do that.”
It’s a common analogy in the science world: Epigenetics is like an invisible piano player hovering over our genetic keyboard, with each key representing a different gene. The pianist controls which keys get pressed, the rhythm and the melody. But what if the musician can be trained to play a different melody? Trained to stop striking the keys that represent diseases such as cancer or diabetes?
As scientists such as Dr. Xu learn more, it’s conceivable therapies will be developed to “stop the music” and replace an off-key melody with a beautiful harmony.
“There is a close association between diabetes and cancer,” Dr. Xu said. “We are focused on a pair of epigenetic programs that could be changed, resulting in treatment of one or both diseases.”
The body’s energy usage is called metabolism. Studies have shown that impaired metabolism, a hallmark of diabetes and obesity, plays an important role in cancer development and progression. For example, the National Institutes of Health estimates that 20 percent of cancer deaths are associated with obesity.
To examine this linkage, Dr. Xu has her eye on a destructive alliance between a pro-cancer protein called EZH2 and a metabolic pathway that acts as a sensor of cell energy, O-GlcNAcylation. A defect there may be the culprit.
The pro-cancer protein EZH2 drives the aggressiveness of cancer cells and may interfere with the energy sensor O-GlcNAc’s function as a metabolic thermostat.
“We want to target the cross-talk of these two and try to cure both cancer and diabetes by making epigenetic changes,” Dr. Xu said.
By regulating the two, it may be possible to reverse the situation to the normal state.
“Kexin’s work has the potential to improve cancer treatment,” said Tim Huang, Ph.D., professor and chairman of molecular medicine. “Epigenetic reprogramming could eliminate drug resistance in cancer patients who are not responding to therapies.”
Once again using the piano player analogy, by prompting the musician to play a different tune or style, a revolutionary cancer drug—or revolutionary diabetes drug—could result.