Dr. Igor Koturbash from the University of Arkansas for Medical Sciences co-authored the paper, “Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications”, which was one of our most accessed articles and he shared some of his insights with us.
Why is this review important?
This review is a first attempt to bring together all the knowledge we have accumulated in the field and to connect findings from the bench with research performed in clinics.
How and/or when did you get into this field of study?
I was raised several hundred miles away from Chornobyl. That predetermined my interest in radiation biology. In regard to repetitive elements… Well, genes cover 1 to 2% of our genomes, but about 99% of scientists work with them; repetitive elements pretty much cover the rest, but only 1 to 2% of scientists pay attention to them. But the complex biology of repetitive elements, their ability not only to litter but also to effectively regulate the genome and their heavy methylation status (the vast majority of DNA methylation stems particularly from repetitive elements) make them one of the most interesting targets for radiation epigenetics.
Where do you see this field in the next 10 years?
Epigenetics is a rapidly evolving field. Epigenetic mechanisms of genetic information regulation are recognized not only in the normal cell, but also in the development of pathological states. On the other hand, epigenetics is so tightly related (inter-related) with many other fields that merging epigenetics with them is unavoidable, and, in fact, this is what we have observed in the last several years. For instance, there is a very tight link between the DNA and histone methylation – key epigenetic mechanisms – and the one-carbon metabolism – one of the central metabolic pathways that, besides its critical role in protein synthesis and response to oxidative stress (i.e., via synthesis of glutathione), provides donors of methyl groups for normal DNA and histone methylation. Knowing the substantial differences in the epigenome and metabolism of normal and cancer cells, harnessing the power of epigenetics and metabolism together promises to significantly improve the radiotherapy, by increasing the normal tissue tolerance to radiation and radiosensitizing the tumorous one.
Is there any particular article you published that launched your career?
For me, every published article is important, but I could probably name the article we published in Radiation Research in 2014 as being crucial to establishing my career. In this collaborative study with Drs. Daohong Zhou from UAMS and Jacob Raber from OHSU, we have shown that exposure to leukemogenic doses of heavy iron ions, despite the absence of genetic damage, leads to long-lasting changes in the epigenome of the hematopoietic stem and progenitor cells. This study confirmed that radiation-induced epigenetic alterations are not random events as they occur only in specific cell types, can be persistent by nature and can lead to development of genomic instability via reactivation of repetitive elements.
Do you have any advice for Postdoctoral Researchers?
My advice will be very simple: Think of what you want to get out of your postdoctoral training. Where do you see yourself in the future? How can you start shaping up your career accordingly? From your first day of postdoctoral training, you should start thinking about your next position and what you need to do in order to achieve this goal, independent of where you see yourself – academia, government or industry.