Randy Jirtle

Early life and career

Jirtle was born in Kewaunee, Wisconsin. He attended Algoma Public High School and the University of Wisconsin–Madison, graduating with a B.S. degree in Nuclear Engineering. For graduate school, he remained at the University of Wisconsin-Madison, obtaining an M.S. in Radiation Biology in 1973 and a PhD in 1976 (Major: Radiation Biology; Minor: Statistics). Following post-doctoral studies, Jirtle was appointed Assistant Professor of Radiology at Duke University in 1980, and became Professor of Radiation Oncology in 1990 and Associate Professor of Pathology in 1998. He remained at Duke until 2012, and is currently Professor of Epigenetics in the Department of Biological Sciences at North Carolina State University, Raleigh, NC, and Senior Scientist at the McArdle Laboratory of Cancer Research, University of Wisconsin in Madison, WI.

Research

Jirtle has long been interested in how environmental agents influence biological systems. His early research examined the influence of radiation on biological systems. He developed the first in vivo clonogenic assay for hepatocytes, and used it to quantify their survival when exposed to X-rays and neutrons. Jirtle also used this clonal assay to study the phenomenon of liver regeneration, and published a book on liver regeneration and carcinogenesis in 1995. These early studies ultimately led to the identification of the insulin-like growth factor receptor (IGF2R) as a human tumor suppressor gene, and to studies in the emerging field of genomic imprinting, since murine IGF2R was shown at that time to be imprinted.

Genomic imprinting is an example of epigenetic inheritance that results in the maternal and paternal copies of certain genes being expressed differently. The evolutionary origin of genomic imprinting has been hotly debated, and the conflict theory was proposed to explain its development. This theory posits that imprinting evolved in response to a genetic ‘battle between the sexes’ to determine the level of maternal resources invested in each offspring. Jirtle examined the imprint status of the IGF2R and IGF2 in what, at the time, were unconventional species (opossum and platypus). The data generated from these phylogenetically informative species are consistent with the evolution of imprinting about 150 million years ago in a common ancestor to Therian mammals (i.e. Metatherians and Eutherians) with the advent of placentation and live birth without the use of a shelled egg, and provide strong support for the conflict theory of imprinting evolution. Imprinted genes have been implicated in complex human disorders such as Alzheimer disease, autism, obesity, diabetes and schizophrenia. Jirtle has contributed to the better understanding of these human conditions by identifying novel imprinted genes, either by biochemical analysis of individual genes or by genome-wide studies that used machine learning-based approaches to predict candidate imprinted genes, followed by biochemical examination of these candidates.

The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that early life experiences can be captured and retained into adulthood, thus influencing the development of adult disease. Jirtle’s most influential scientific accomplishment is a series of papers in which his use of the Agouti mouse experimental system demonstrates that the ‘memory system’ for this phenomenon involves epigenetic modifications.

In 2003, he provided convincing molecular evidence that maternal dietary supplementation of Agouti viable yellow (A^vy) mice with methyl donors (i.e. folic acid, choline, vitamin B₁₂, and betaine) altered the coat color distribution and disease susceptibility in genetically identical offspring by increasing DNA methylation at the A^vy locus. This paper is classified as a ‘Highly Cited Paper’ in Essential Science Indicators from Thomson Reuters, and was one of the key papers in ScienceWatch’s Special Topics Research Front Map on Epigenetic Gene Regulation (2009). A subsequent study showed that the phyto-estrogen, genistein, modifies the fetal epigenome, alters coat color, and protects Agouti offspring from obesity even though it is not capable of donating a methyl group. This article was selected as the ‘Classic Paper of the Year’ in 2011 by Environmental Health Perspectives. It was followed by a study that showed that genistein and methyl donor supplementation can counteract detrimental epigenetic effects induced by a controversial xenobiotic chemical, bisphenol A (BPA). Returning to his radiation biology training, Jirtle recently used the A^vy mouse system to show that embryonic stem cells exposed in vivo to low doses of a physical agent, X-rays, induce positive adaptive responses in the offspring by altering the epigenome, and that these changes are mitigated by antioxidants. Together these studies were instrumental in ushering in the era of environmental epigenomics by demonstrating that nutritional, chemical, and physical agents can alter disease susceptibility in adulthood by modifying the epigenome.

Awards and Leadership

Jirtle has published many peer-reviewed manuscripts in the field of epigenetics. He has been an invited speaker at numerous national and international meetings, and has presented a number of named lectureships. He has organized several international scientific meetings including, in 2005, a seminal conference entitled ‘Environmental epigenomics, imprinting and disease susceptibility’ and, in 2011, a Keystone Meeting entitled ‘Environmental Epigenomics and Disease Susceptibility’. He was honored in 2006 with the Distinguished Achievement Award from the College of Engineering at the University of Wisconsin-Madison. His research on the Agouti mouse system was prominently featured in the PBS NOVA program ‘Ghost in Your Genes’, originally broadcast in 2007. Jirtle presented the NIH Director’s WALS lecture in 2012 entitled Epigenetics: How Genes and Environment Interact. In 2013, he participated in the epigenetic session Destiny and DNA: Our Pliable Genome at the World Science Festival in New York City. He has edited a book on Liver Regeneration and Carcinogenesis, and two books on Environmental Epigenomics in Health and Disease. Dr. Jirtle received the Linus Pauling Award from the Institute of Functional Medicine in 2014. Jirtle is on the Editorial Board of the journal Environmental Epigenetics published by Oxford University Press.

In 2007 Jirtle was nominated to be Time Magazine’s Person of the Year by Dr. Nora Volkow, Director of the National Institute on Drug Abuse. In her nomination, she stated “I’d select the Duke University scientist whose pioneering work in epigenetics and genomic imprinting has uncovered a vast territory in which a gene represents less of an inexorable sentence and more of an access point for the environment to modify the genome. The trailblazing discoveries of Dr. Jirtle have produced a far more complete and useful understanding of human development and diseases”.