Randy Jirtle

Last updated
Randy L. Jirtle
200128 Randy Jirtle 044.jpg
Randy Jirtle in 2020
Born (1947-11-09) November 9, 1947 (age 76)
Kewaunee, Wisconsin, U.S.
Alma materUniversity of Wisconsin-Madison
Known forEvolution of genomic imprinting and identifying imprinted genes. Showing that environmental agents alter the epigenome, thereby affecting health and disease susceptibility in adulthood.
Scientific career
FieldsEpigenetics, Genomic imprinting, Radiation biology
InstitutionsDuke University, University of Wisconsin-Madison, University of Bedfordshire, North Carolina State University, University of Adelaide
Website www.geneimprint.com

Randy Jirtle (born November 9, 1947) is an American biologist noted for his research in epigenetics, the branch of biology that deals with inherited information that does not reside in the nucleotide sequence of DNA. [1] Jirtle retired from Duke University, Durham, NC in 2012. He is presently Professor of Epigenetics in the Department of Biological Sciences at North Carolina State University, Raleigh, NC. [2] Jirtle is noted for his research on genomic imprinting, and for his use of the Agouti mouse model to investigate the effect of environmental agents on the mammalian epigenome and disease susceptibility.

Contents

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. [2]

Research

Jirtle's early research examined the influence of radiation on biological systems. He developed the first in vivo clonogenic assay for hepatocytes, [3] and used it to quantify their survival when exposed to X-rays [4] [5] and neutrons. [6] Jirtle also used this clonal assay to study the phenomenon of liver regeneration. [7] These early studies ultimately led to the identification of the insulin-like growth factor receptor (IGF2R) as a human tumor suppressor gene, [8] [9] and to studies in the emerging field of genomic imprinting, since murine IGF2R was shown at that time to be imprinted. [10]

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 [11] [12] [13] .

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 [14] . The group has now developed a custom methylation array to allow targeted investigation of the ICRs of the human imprintome [15] ]. 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 [16] .

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. [17] [18] A subsequent study [19] 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. [20] [21] This article was selected as the ‘Classic Paper of the Year’ in 2011 by Environmental Health Perspectives. [22] 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). [23] 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. [24] [25]

Agouti Mice These mice are genetically identical despite looking phenotypically different. The mouse on the left's mother was fed Bisphenol A (BPA) with a normal mouse diet and the mouse on the right's mother was fed BPA with a methyl-rich diet. The left mouse is yellow and obese, while the right mouse is brown and healthy. Agouti Mice.jpg
Agouti Mice These mice are genetically identical despite looking phenotypically different. The mouse on the left's mother was fed Bisphenol A (BPA) with a normal mouse diet and the mouse on the right's mother was fed BPA with a methyl-rich diet. The left mouse is yellow and obese, while the right mouse is brown and healthy.

He has edited a book on Liver Regeneration and Carcinogenesis, [26] and two books on Environmental Epigenomics in Health and Disease. [27] [28] Jirtle is on the editorial board of the journals Epigenomics published by Taylor & Francis, [29] Epigenetics published by Taylor & Francis, [30] and Environmental Epigenetics published by Oxford University Press. [31]

Awards

Jirtle has received a number of awards in recognition of his achievements. He was honored in 2006 with the Distinguished Achievement Award from the College of Engineering at the University of Wisconsin-Madison. [32] 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. [33] He was a featured scientist on the PBS NOVA television program on epigenetics in 2007 entitled Ghost in Your Genes. [34] He was the inaugural recipient of the Epigenetic Medicine Award. [35] In 2009, Jirtle received the STARS Lecture Award in Nutrition and Cancer from the National Cancer Institute. [36] Dr. Jirtle was invited in 2012 to present the NIH Director’s WALS lecture. [37] He received the Linus Pauling Award from the Institute of Functional Medicine in 2014. [38] ShortCutsTV produced a documentary in 2017 based upon Jirtle’s epigenetic research entitled, Are You What Your Mother Ate? The Agouti Mouse Study [39] He received in 2018 the Northern Communities Health Foundation Visiting Professorship Award at University of Adelaide in Australia. [40] Personalized Lifestyle Medicine Institute presented Jirtle with the Research and Innovation Leadership Award in 2019. [41] In 2019, he also received the Alexander Hollaender Award [42] from the Environmental Mutagenesis and Genomics Society stating, “The award recognizes Dr. Jirtle’s discovery that the environment can influence inheritance of phenotypic traits through epigenetic reprogramming representing one of the most important scientific advances of the 21st century.”

Related Research Articles

Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the female or male parent. Genes can also be partially imprinted. Partial imprinting occurs when alleles from both parents are differently expressed rather than complete expression and complete suppression of one parent's allele. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. In 2014, there were about 150 imprinted genes known in mice and about half that in humans. As of 2019, 260 imprinted genes have been reported in mice and 228 in humans.

<span class="mw-page-title-main">Epigenetics</span> Study of DNA modifications that do not change its sequence

In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. Epigenetic factors can also lead to cancer.

A maternal effect is a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother. In genetics, maternal effects occur when an organism shows the phenotype expected from the genotype of the mother, irrespective of its own genotype, often due to the mother supplying messenger RNA or proteins to the egg. Maternal effects can also be caused by the maternal environment independent of genotype, sometimes controlling the size, sex, or behaviour of the offspring. These adaptive maternal effects lead to phenotypes of offspring that increase their fitness. Further, it introduces the concept of phenotypic plasticity, an important evolutionary concept. It has been proposed that maternal effects are important for the evolution of adaptive responses to environmental heterogeneity.

<span class="mw-page-title-main">Epigenome</span> Biological term

In biology, the epigenome of an organism is the collection of chemical changes to its DNA and histone proteins that affects when, where, and how the DNA is expressed; these changes can be passed down to an organism's offspring via transgenerational epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome. The human epigenome, including DNA methylation and histone modification, is maintained through cell division. The epigenome is essential for normal development and cellular differentiation, enabling cells with the same genetic code to perform different functions. The human epigenome is dynamic and can be influenced by environmental factors such as diet, stress, and toxins.

<span class="mw-page-title-main">Agouti-signaling protein</span> Protein-coding gene in the species Homo sapiens

Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte produces phaeomelanin, or eumelanin. This interaction is responsible for making distinct light and dark bands in the hairs of animals such as the agouti, which the gene is named after. In other species such as horses, agouti signalling is responsible for determining which parts of the body will be red or black. Mice with wildtype agouti will be grey-brown, with each hair being partly yellow and partly black. Loss of function mutations in mice and other species cause black fur coloration, while mutations causing expression throughout the whole body in mice cause yellow fur and obesity.

<span class="mw-page-title-main">Computational epigenetics</span>

Computational epigenetics uses statistical methods and mathematical modelling in epigenetic research. Due to the recent explosion of epigenome datasets, computational methods play an increasing role in all areas of epigenetic research.

Nutriepigenomics is the study of food nutrients and their effects on human health through epigenetic modifications. There is now considerable evidence that nutritional imbalances during gestation and lactation are linked to non-communicable diseases, such as obesity, cardiovascular disease, diabetes, hypertension, and cancer. If metabolic disturbances occur during critical time windows of development, the resulting epigenetic alterations can lead to permanent changes in tissue and organ structure or function and predispose individuals to disease.

The Epigenomics database at the National Center for Biotechnology Information was a database for whole-genome epigenetics data sets. It was retired on 1 June 2016.

The International Human Epigenome Consortium (IHEC) is a scientific organization, founded in 2010, that helps to coordinate global efforts in the field of Epigenomics. The initial goal was to generate at least 1,000 reference (baseline) human epigenomes from different types of normal and disease-related human cell types.

<span class="mw-page-title-main">Epigenome editing</span>

Epigenome editing or epigenome engineering is a type of genetic engineering in which the epigenome is modified at specific sites using engineered molecules targeted to those sites. Whereas gene editing involves changing the actual DNA sequence itself, epigenetic editing involves modifying and presenting DNA sequences to proteins and other DNA binding factors that influence DNA function. By "editing” epigenomic features in this manner, researchers can determine the exact biological role of an epigenetic modification at the site in question.

<span class="mw-page-title-main">Frances Champagne</span> Psychologist

Frances A. Champagne is a Canadian psychologist and University Professor of Psychology at the University of Texas at Austin known for her research in the fields of molecular neuroscience, maternal behavior, and epigenetics. Research in the Champagne lab explores the developmental plasticity that occurs in response to environmental experiences. She is known for her work on the epigenetic transmission of maternal behavior. Frances Champagne's research has revealed how natural variations in maternal behavior can shape the behavioral development of offspring through epigenetic changes in gene expression in a brain region specific manner. She won the NIH Director's New Innovator Award in 2007 and the Frank A. Beach Young Investigator Award in Behavioral Neuroendocrinology in 2009. She has been described as the "bee's knees of neuroscience". She serves on the Committee on Fostering Healthy Mental, Emotional, and Behavioral Development Among Children and Youth in the United States.

<span class="mw-page-title-main">Epigenome-wide association study</span>

An epigenome-wide association study (EWAS) is an examination of a genome-wide set of quantifiable epigenetic marks, such as DNA methylation, in different individuals to derive associations between epigenetic variation and a particular identifiable phenotype/trait. When patterns change such as DNA methylation at specific loci, discriminating the phenotypically affected cases from control individuals, this is considered an indication that epigenetic perturbation has taken place that is associated, causally or consequentially, with the phenotype.

George K. Michalopoulos is a Greek-American pathologist and academic. He served as Maud L. Menten Professor of Experimental Pathology and Chair of the Department of Pathology at the University of Pittsburgh and UPMC from 1991 to 2023.

<span class="mw-page-title-main">Anne Ferguson-Smith</span> Mammalian developmental geneticist (born 1961)

Anne Carla Ferguson-Smith is a mammalian developmental geneticist. She is the Arthur Balfour Professor of Genetics and Pro-Vice Chancellor for Research and International Partnerships at the University of Cambridge. Formerly head of the Department of Genetics at the University of Cambridge, she is a Fellow of Darwin College, Cambridge and serves as President of the Genetics Society.

<span class="mw-page-title-main">Bradley Bernstein</span> Biologist

Bradley E. Bernstein is a biologist and Professor of Cell Biology at Harvard Medical School. He is Chair of the Department of Cancer Biology at the Dana–Farber Cancer Institute and the Director of the Broad Institute's Gene Regulation Observatory. He is known for contributions to the fields of epigenetics and cancer biology.

Azim Surani is a Kenyan-British developmental biologist who has been Marshall–Walton Professor at the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge since 1992, and Director of Germline and Epigenomics Research since 2013.

<span class="mw-page-title-main">Manolis Kellis</span> Greek-born computational biologist

Manolis Kellis is a professor of Computer Science and Computational Biology at the Massachusetts Institute of Technology (MIT) and a member of the Broad Institute of MIT and Harvard. He is the head of the Computational Biology Group at MIT and is a Principal Investigator in the Computer Science and Artificial Intelligence Lab (CSAIL) at MIT.

<span class="mw-page-title-main">Epigenetic priming</span> Type of modification to a cells epigenome

Epigenetic priming is the modification to a cell's epigenome whereby specific chromatin domains within a cell are converted from a closed state to an open state, usually as the result of an external biological trigger or pathway, allowing for DNA access by transcription factors or other modification mechanisms. The action of epigenetic priming for a certain region of DNA dictates how other gene regulation mechanisms will be able to act on the DNA later in the cell’s life. Epigenetic priming has been chiefly investigated in neuroscience and cancer research, as it has been found to play a key role in memory formation within neurons and tumor-suppressor gene activation in cancer treatment respectively.

Folami Ideraabdullah is an American geneticist and assistant professor in the Department of Genetics and the Department of Nutrition at the Gillings School of Global Public Health at the University of North Carolina at Chapel Hill. Ideraabdullah explores how maternal nutrition and environmental toxin exposure affect development through exploring epigenetic changes to DNA. She has found that maternal Vitamin D deficiencies can cause genome-wide changes in methylation patterns that persist for several generations and impact offspring health. Her international collaboration with the University of Witwatersrand represents the first time that metal levels in the placenta have been investigated in relation to birth outcomes in South Africa.

Nutritional epigenetics is a science that studies the effects of nutrition on gene expression and chromatin accessibility. It is a subcategory of nutritional genomics that focuses on the effects of bioactive food components on epigenetic events.

References

  1. ↑ Allis, CD, Jenuwein T, Reinberg D, Caparros, M-L (eds.) (2007), Epigenetics, Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press, ISBN   0879698756
  2. 1 2 "Alumnus Randy Jirtle receives 2019 Alexander Hollaender Award" https://www.engr.wisc.edu/alumnus-randy-jirtle-receives-2019-alexander-hollaender-award/ College of Engineering - University of Wisconsin-Madison 1 March 2019
  3. ↑ Jirtle RL, Biles C, Michalopoulos G (1980), "Morphologic and histochemical analysis of hepatocytes transplanted into syngeneic hosts", Am J Pathol101: 115–126. PMID   6108719
  4. ↑ Jirtle RL, Michalopoulos G, McLain JR, Crowley J (1981), "Transplantation system for determining the clonogenic survival of parenchymal hepatocytes exposed to ionizing radiation", Cancer Res41: 3512–3518. PMID   7020930
  5. ↑ Jirtle RL, McLain JR, Strom SC, Michalopoulos G (1982), "Repair of radiation damage in noncycling parenchymal hepatocytes", Br J Radiol55: 847–851. PMID   6753999
  6. ↑ Jirtle RL, Michalopoulos G, Strom SC, DeLuca PM, Gould MN (1984), "The survival of parenchymal hepatocytes irradiated with low and high LET radiation", Br J Cancer Suppl6: 197–201. PMID   6692410
  7. ↑ Jirtle RL, Michalopoulos G (1982), "Effects of partial hepatectomy on transplanted hepatocytes", Cancer Res.42: 3000–3004. PMID   7046913
  8. ↑ De Souza AT, Hankins GR, Washington MK, Orton TC, Jirtle RL (1995), "M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity", Nat Genet11: 447–449. PMID   7493029
  9. ↑ Hankins GR, De Souza AT, Bentley RC, Patel MR, Marks JR, Iglehart JD, Jirtle RL (1996), "M6P/IGF2 receptor: a candidate breast tumor suppressor gene", Oncogene12: 2003–2009. PMID   8649861
  10. ↑ Barlow DP, Stoger R, Herrmann BG, Saito K, Schweifer N (1991), "The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme[ sic ] locus", Nature349: 84–87. PMID   1845916
  11. ↑ Killian et al. 2000 (https://pubmed.ncbi.nlm.nih.gov/10882106/)
  12. ↑ Killian et al. 2001 (https://pubmed.ncbi.nlm.nih.gov/11479919/)
  13. ↑ Nolan et al. 2001 (https://pubmed.ncbi.nlm.nih.gov/11455432/)
  14. ↑ Jima et al. 2022 (https://www.tandfonline.com/doi/full/10.1080/15592294.2022.2091815)]
  15. ↑ Carreras-Gallo et al. 2024 (https://link.springer.com/article/10.1186/s43682-024-00028-6)
  16. ↑ Cevik et al. 2024 (https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-024-01672-4)]
  17. ↑ Waterland RA, Jirtle RL (2003), "Transposable elements: targets for early nutritional effects on epigenetic gene regulation", Mol Cell Biol23: 5293–5300. PMID   12861015
  18. ↑ Blakeslee, Sandra (October 7, 2003). "A Pregnant Mother's Diet May Turn the Genes Around". The New York Times.
  19. ↑ Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL (2006), "Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome", Environ Health Perspect114: 567–572. PMID   16581547
  20. ↑ "Prenatal Genistein in Soy Reduces Obesity in Offspring".
  21. ↑ "Folate Shields Fetus Against Chemical in Plastics". The Washington Post . HealthDay News. July 31, 2007. Retrieved July 3, 2022.
  22. ↑ Tilson HA (2011), "EHP Classic Paper of the Year, 2011", Environ Health Perspect119: A238. PMID   21628120
  23. ↑ Dolinoy DC, Huang D, Jirtle RL (2007), "Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development", PNAS104: 13056–13061. PMID   17670942
  24. ↑ Bernal AJ, Dolinoy DC, Huang D, Skaar DA, Weinhouse C, Jirtle RL (2013), "Adaptive radiation-induced epigenetic alterations mitigated by antioxidants", FASEB J27: 665–671. PMID   23118028
  25. ↑ "Low Dose Radiation-Induced Epigenetic Alterations Found in Agouti Mouse Model". US Department of Energy. November 8, 2007. Retrieved May 23, 2013.
  26. ↑ Jirtle, RL, ed. (1995), Liver Regeneration and Carcinogenesis: Cellular and Molecular Mechanisms, San Diego: Academic Press, ISBN   012388649X
  27. ↑ Jirtle, RL; Tyson, FL, eds. (2013), Environmental Epigenomics in Health and Disease: Epigenetics and Disease Origins, Heidelberg: Springer, ISBN   978-3642233791
  28. ↑ Jirtle, RL; Tyson, FL, eds. (2013), Environmental Epigenomics in Health and Disease: Epigenetics and Complex Diseases Origins, Heidelberg: Springer, ISBN   978-3642368264
  29. ↑ "Epigenomics".
  30. ↑ "Epigenomics".
  31. ↑ "Environmental Epigenetics". Environmental Epigenetics Editorial Board. Archived from the original on June 13, 2015. Retrieved April 17, 2015.
  32. ↑ "2006 Distinguished career award: Randy Jirtle - College of Engineering - University of Wisconsin-Madison". www.engr.wisc.edu. Archived from the original on September 9, 2016.
  33. ↑ "Person of the Year 2007". Time Magazine. November 8, 2007. Retrieved May 23, 2013.
  34. ↑ "Ghost in Your Genes". PBS .
  35. ↑ "Article: New Epigenetic Science Award Presented in Groundbreaking Ceremony". OpEd News. May 30, 2008. Retrieved July 3, 2022.
  36. ↑ "NIH VideoCast - Epigenetics, Nutrition and Disease Susceptibility". September 29, 2009.
  37. ↑ "NIH VideoCast - Epigenetics: How Genes and Environment Interact". April 18, 2012.
  38. ↑ "Randy Jirtle, PHD, Receives Linus Pauling Award".
  39. ↑ "Are You What Your Mother Ate?". shortcutstv.com.
  40. ↑ Archived at Ghostarchive and the Wayback Machine : Epigenetic Origins of Human Health, Professor Randy Jirtle. YouTube .
  41. ↑ "2019 Thought Leaders Consortium Schedule | PLM Institute". plminstitute.org. Archived from the original on March 2, 2019.
  42. ↑ "EMGS is Proud to Announce the 2019 Alexander Hollaender and EMGS Award Recipients".

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