Jirtle's 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. 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. Jirtle initially took a phylogenetic approach to the study of genomic imprinting, examining allelic expression, in a range of mammalian orders (and in non-mammalian vertebrates), of the genes encoding the IGF2R (also known as the cation-independent mannose 6-phosphate receptor, CI-MPR) and its ligand, IGF2. He was the first to show that imprinting arose in an ancestor of metatherian and therian mammals, which feature placentation and live birth, but is not a feature of prototherian (egg-laying) mammals. Parent-of-origin-dependent monoallelic expression of imprinted genes is regulated by imprinted control regions (ICRs) which are differentially methylated during
gametogenesis, and the Jirtle laboratory recently identified 1,488 hemi-methylated candidate imprint control regions (ICRs) in the human genome - the human imprintome. The group has now developed a custom methylation array to allow targeted investigation of the ICRs of the human imprintome ]. The availability of this research tool will be useful in determining the contribution of imprinted genes to human health, and to diseases and disorders such as Alzheimer’s disease. In 2003, Jirtle provided molecular evidence that maternal dietary supplementation of Agouti viable yellow (Avy) 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 Avy locus. 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). Jirtle used the Avy 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. He has edited a book on Liver Regeneration and Carcinogenesis, and two books on Environmental Epigenomics in Health and Disease. Jirtle is on the editorial board of the journals Epigenomics published by Taylor & Francis, Epigenetics published by Taylor & Francis, and Environmental Epigenetics published by Oxford University Press. == Awards==