Fighting Cancer Against the Clock
For Cheryl Walker, Ph.D., and her team, timing is everything.
She knows what the bad guys are: specifically endocrine disrupting chemicals, or EDCs. EDCs exhibit hormone-like properties that can wreak havoc via the endocrine system, either by acting like a hormone, blocking a hormone, or causing cancer in an endocrine organ. And they can be found in anything from pesticides to water bottles (like BPA or Bisphenol A—a man-made carbon-based synthetic compound used to make certain plastics and epoxy resins). It’s fair to say Dr. Walker knows exactly what the bad guys are up to.
It’s when those EDCs strike that she and her team find most compelling.
Dr. Walker received her Ph.D. in Cell Biology with a focus on epigenetics, and for the past 10 years has studied the link between genetics and environmental disease. She’s now the Director of the Texas A&M Health Science Center Institute of Biosciences and Technology, and her lab is part of the Center for Translational Cancer Research, all located in Houston’s Texas Medical Center. Through support by the National Institutes of Health and the Cancer Prevention Research Institute of Texas, she and her lab focus on how cancer happens at the molecular level, especially how the interaction between genes, the epigenome and the environment cause this disease.
“The DNA we inherit is like computer hardware. What runs the ‘computer’ is the software—the epigenome. In early life, as embryos or infants, this epigenetic programming that runs our genome is being “installed” on the genome of developing cells and tissues” Walker explains. “Even a short exposure to EDCs early in life can disrupt the ‘install’ of the epigenetic software, altering the function of our genome in a way that increases our risk of disease in adulthood.”
Walker’s team gathered preliminary data using a rodent model to study the long-term effects of exposures to EDCs early in life. These studies showed that animals exposed to EDCs shortly after birth exhibited life-long changes in their epigenome. As a result, they were at much greater risk for uterine cancer as adults and also became obese. Particularly, if these animals’ calories were restricted by 30 percent, their risk of uterine cancer returned to normal.
These findings illustrate some important points: First, that early life exposure to EDCs can “reprogram” our epigenome, so that later in life we are more susceptible to diseases—especially cancer. Secondly, the relationship between obesity and cancer form a two-pronged mechanism that has many implications for research. Lastly, early lifestyle interventions can possibly reverse the bad “reprogramming” by EDCs to decrease risk of disease.
Today the concern is that exposure to EDCs is quite widespread, but overall, levels are low. EDCs like BPA have even been found in the umbilical cords of infants. Many EDCs such as BPA mimic estrogen, and to women of reproductive age, a small dose of BPA would probably not have negative effects. However, to an infant who would not normally be exposed to estrogen during critical periods of development, even a low level exposure to BPA has the potential to reprogram the epigenome.
It is this potential for epigenetic impairment in early life that Walker and her team explore. To them, it’s not the “what,” but the when that produces the most intriguing research questions.
“Early life development is such a critical time for ‘installation’ of epigenetic programming, and this epigenetic programming is then carried with us for life,” Walker emphasizes. “It is a new and important area of research for understanding environmental causes of disease.”
This concept that environment and exposure can determine our health lies at the heart of Texas A&M’s One Health initiative. Humans and their environment are inextricably linked—at all stages of life.
The good news is that the epigenome is very plastic, Walker asserts. Epigenetic markers can be changed. In essence, they can be reprogrammed. This plasticity of the epigenome also provides opportunities for disease prevention and intervention. If the epigenome gets reprogrammed in a negative way, scientists are now studying how to implement epigenetic therapies and interventions to reverse the reprogramming, ultimately reducing the risk of disease in at-risk people. Ultimately epigenetics is a viable target for therapies to help reduce risk of cancer and other diseases.
Next, Dr. Walker and her team will build upon their recent research to test other interventions such as exercise or drugs that mimic caloric restriction to see if they can “correct” defects induced by EDCs during developmental reprogramming.
“Through these additional studies we hope to identify the most effective interventions to reverse epigenetic reprogramming of the genome,” says Walker.
*Story credit: Lindsey Bertrand*