Epigenetics is a popular, yet still mysterious concept in health and medicine. It’s the study of a variety of biological processes that alter the expression of our genes. Sometimes this involves modifying the structure of our chromosomes to mask or unmask genes, and other times the actual genetic code is changed in certain cells. Harold C. Smith, Ph.D., a longtime professor of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry has studied epigenetics in a research focus known as RNA and DNA editing since it was introduced two decades ago. He was invited to write a commentary on the progress and future of this research, published today in Trends in Biochemical Sciences, and answers a few questions about the subject.
Q: Why is the study of epigenetics important?
Smith: We’re all born with a set of genes. If those genes were all you had, you’d have a very limited ability to address the diversity that you encounter in everyday life. For example, we are born with one gene for making antibodies – proteins that help our bodies fight viruses, bacteria and other foreign invaders. But, over a lifetime of exposure to different bugs that cause colds, the flu, and other infections, we end up making close to a billion different antibodies. This is possible because of epigenetics that involves DNA editing; an enzyme within our body changes the genetic code of the antibody producing gene in white blood cells, allowing us to adapt and create new antibodies every time we are challenged by something in the environment.
Epigenetic changes are necessary for typical development and health, but they can also cause disease. Understanding the good and the bad epigenetic changes that take place in our bodies could help us develop new treatments for many diseases like cancer, heart disease and HIV.
Q: Epigenetics is a broad field. What does your research focus on?
Smith: People are probably familiar with environmental epigenetics, where environmental factors like diet and exposure to pesticides, drugs, smoke and other toxins change the behavior of genes. For the past 20 years, my lab has focused on a group of RNA editing enzymes called the APOBEC family of enzymes that alter our genetic code at either the level of DNA or RNA. Everyone has these enzymes and we believe that their main function is to help the body fight disease. We’ve found that if our bodies don’t control these enzymes properly, they can turn on us and cause conditions like cancer. An area where we have and continue to make major contributions is in the structure of APOBEC enzymes, which determines how they work and how they are controlled.
Q: Are treatments based on epigenetics coming to the clinic anytime soon?
Smith: Even though we’ve studied epigenetics for 20 years, there is still so much that we don’t know. For example, we don’t understand how APOBEC enzymes fine tune the expression of specific genes to help us fight disease. Understanding what happens when APOBEC enzymes go awry and lead to genetic changes that cause cancer is even more difficult. So, we have a long way to go.
HIV is one area where we are making good progress. Research in my lab has focused on how the HIV protein dubbed “Vif” (for viral infectivity factor) tricks the body into destroying APOBEC enzymes, as if they were cellular waste. If Vif was not present, we could defend ourselves against an HIV infection. This is because in the absence of Vif, scientists around the world have shown that APOBEC enzymes can defeat HIV by scrambling up the virus's genetic code. We’re currently looking for drugs that can target and eliminate Vif so that the APOBEC enzymes can perform their job against HIV.
Smith (pictured) organized the first major conference on the topic – the Gordon Research Conference (GRC) on RNA Editing – in 1997 and continues to blaze trails in the field through research and by training the next generation of scientists. Next year marks the 20th anniversary of the GRC on RNA and DNA Editing.
“Dr. Smith was interested in epigenetics and RNA editing as a gene control mechanism long before it was a popular area,” says Jeffrey J. Hayes, Ph.D., chair and Shohei Koide Professor of the Department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry. “RNA editing is currently recognized as playing a role in many important biological functions, including as a defense against viruses such as HIV. Dr. Smith was a pioneer in getting the field started and he continues to make important contributions.”
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