Epigenetics is a novel, rapidly growing field of biology and medicine that is transforming our understanding of life. This exciting area focuses on stable changes in gene expression that take place without altering the primary DNA sequence. It uses reversible chemical marks on DNA and DNA-associated proteins to determine which genes are “turned on” and which genes are “turned off” in a given tissue or during a given developmental stage. While our genes constitute the “hardware” of the genome, epigenetics can be compared to computer software.
Epigenetics is a rapidly growing field. Other universities were jumping on board, and I wanted the University of Minnesota to be leading the way, ” said Natalia Tretyakova, PhD.
Epigenetics holds great potential in prevention and treatment of human diseases, regenerative medicine, and epidemiology. It has already made a major impact in the way we diagnose and treat cancer.
Natalia Tretyakova, PhD, is a Distinguished McKnight professor with the Department of Medicinal Chemistry within the College of Pharmacy, and a Masonic Cancer Center member. She was trained as a nucleic acids chemist and dedicated most of her research career to studies of DNA damage and repair. Her interest in structural modifications of DNA led her to the world of epigenetics several years ago.
“It’s amazing how many areas of scientific inquiry are affected by epigenetics. I’ve met people working in agriculture, studying gene regulation in corn, epidemiologists uncovering risk factors for disease, pharmacologists investigating the origins of addiction, and medicinal chemists developing epigenetic therapies,” said Tretyakova. “Other universities were jumping on board, and I wanted the University of Minnesota to be leading the way.”
The Epigenetics Consortium was created in 2015, with financial support from the College of Pharmacy; the Department of Medicinal Chemistry; and the Department of Biochemistry, Molecular Biology, and Biophysics. The goals of the consortium are threefold: understand the epigenetic origin of diseases; develop new treatments; and overcome drug resistance. The interprofessional group spans across the College of Pharmacy; College of Biological Sciences; College of Veterinary Medicine; Medical School; College of Science and Engineering; and the College of Food, Agricultural and Natural Resource Sciences.
The Epigenetics Consortium
“The consortium has enabled new connections, an opportunity to share knowledge, and introduced consortium members to researchers in seemingly unrelated fields who are willing to help each other,” said Tretyakova.
Tretyakova leads the consortium and studies cancer, more specifically, the chemical mechanisms of cancer, the impact of chemical exposures on DNA structure, and the dynamics of epigenetic modifications of DNA. In cancer, epigenetic deregulation contributes to uncontrolled growth of abnormal cells. Mainstay cancer treatments include chemotherapy and radiation to kill cancer cells, but these come at a high cost to the patient due to lasting side effects.
“With future epigenetic therapies, we wouldn’t have to kill cancerous cells, we could rewire them to become ‘normal’ again by reprograming their epigenome, effectively reversing or curing cancer,” said Tretyakova.
In addition to cancer, epigenetics plays a profound role in other human diseases including autism, Alzheimer’s, and chemical addiction.
“I’ve been at the University for 20 years, and in all that time I never met as many people from different disciplines as I have through the consortium. It has enabled new connections, an opportunity to share knowledge, and introduced consortium members to researchers in seemingly unrelated fields who are willing to help each other,” said Tretyakova.
The consortium was started with the Epigenetics Symposium in April 2016. The consortium now holds monthly seminars on broad topics of interest relating to epigenetics in human disease. These seminars bring together expertise from across the University, as well as guest speakers from different universities and institutes around the nation to share the latest findings in epigenetics research and innovation.
Recently, the Epigenetics Consortium partnered with the Mayo Clinic Center for Individualized Medicine Epigenomics Program. The two groups transmit seminars between campuses and plan to organize a joint symposium to be held in Minneapolis in 2020. Hormel Institute’s Cancer Epigenetics & Experimental Therapeutics faculty are also engaged in research collaborations with the consortium, which recently led to joint funding from the NIH.
“Our goal is to continue growing. My philosophy when I started the consortium was not to limit it to one specific area. Epigenetics touches all corners of the University, and is very difficult to silo,” said Tretyakova. “This field presents an amazing opportunity in terms of disease prevention and therapeutic intervention, potentially bringing in new research funding and attracting new talent. The interest shown in epigenetics by young people in particular shows that the future of epigenetics research is bright.”
Nature vs. Nurture
We all born with a set of genes. To what extent these genes are expressed is controlled by epigenetics, which in turn, is affected by countless factors such as diet, stress, aging, exercise, drugs, and our environment.
“While we can’t easily change the genes we are born with, research shows that epigenetic changes are reversible and that’s what’s most exciting,” said Tretyakova.
The NASA Twin Study explored the impacts of spaceflight on a human body and demonstrated the influence of the environment on gene expression. In 2015, Scott Kelly spent a year in space. His identical twin, Mark, stayed behind on the pale blue dot otherwise known as Earth. The twins are both retired astronauts. During Scott’s tenure at the space station, his epigenome had changed in comparison to Mark’s at the molecular level— expression levels of 7 percent of his genes were affected.
Changes in our epigenome can impact generations to come. Take, for example, a study referred to as The Dutch Winter Study. A Dutch famine occurred during 1944 to 1945 under Nazi occupation of the Netherlands. More than 20,000 people died of starvation. When pregnant women gave birth during the famine, their children were especially vulnerable later in life to obesity, diabetes, and schizophrenia. Follow up studies discovered that because of the famine experienced in utero, certain genes were silenced or turned off, and these epigenetic changes persisted through future generations, affecting future disease risk.
“While we can’t easily change the genes we are born with, research shows that epigenetic changes are reversible, and that is what’s most exciting,” said Tretyakova. “Your genes don’t have to determine your future.”