Randy Jirtle

Last updated
Randy L. Jirtle
200128 Randy Jirtle 044.jpg
Randy Jirtle in 2020
Born (1947-11-09) November 9, 1947 (age 74)
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 Professor of Epigenetics in the Department of Biological Sciences at North Carolina State University, Raleigh, NC, and Senior Visiting Scientist at the McArdle Laboratory of Cancer Research, University of Wisconsin, Madison, WI. [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] and Senior Scientist at the McArdle Laboratory of Cancer Research, University of Wisconsin in Madison, WI.

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]

In 2003, he 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. [11] [12] A subsequent study [13] 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. [14] [15] This article was selected as the ‘Classic Paper of the Year’ in 2011 by Environmental Health Perspectives. [16] 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). [17] 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. [18] [19]

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, [20] and two books on Environmental Epigenomics in Health and Disease. [21] [22] Jirtle is on the editorial board of the journals Epigenomics published by Future Medicine, [23] Epigenetics published by Taylor & Francis, [24] and Environmental Epigenetics published by Oxford University Press. [25]

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. [26] 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. [27] He was a featured scientist on the PBS NOVA television program on epigenetics in 2007 entitled Ghost in Your Genes. [28] He was the inaugural recipient of the Epigenetic Medicine Award. [29] In 2009, Jirtle received the STARS Lecture Award in Nutrition and Cancer from the National Cancer Institute. [30] Dr. Jirtle was invited in 2012 to present the NIH Director’s WALS lecture. [31] He received the Linus Pauling Award from the Institute of Functional Medicine in 2014. [32] ShortCutsTV produced a documentary in 2017 based upon Jirtle’s epigenetic research entitled, Are You What Your Mother Ate? The Agouti Mouse Study [33] He received in 2018 the Northern Communities Health Foundation Visiting Professorship Award at University of Adelaide in Australia. [34] Personalized Lifestyle Medicine Institute presented Jirtle with the Research and Innovation Leadership Award in 2019. [35] In 2019, he also received the Alexander Hollaender Award [36] 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

Epigenetics Study of DNA modifications that do not change its sequence

In biology, epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic basis for inheritance. Epigenetics most often involves changes that affect gene activity and expression, but the term can also be used to describe any heritable phenotypic change. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors, or be part of normal development.

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.

Non-Mendelian inheritance Type of pattern of inheritance

Non-Mendelian inheritance is any pattern of inheritance in which traits do not segregate in accordance with Mendel's laws. These laws describe the inheritance of traits linked to single genes on chromosomes in the nucleus. In Mendelian inheritance, each parent contributes one of two possible alleles for a trait. If the genotypes of both parents in a genetic cross are known, Mendel's laws can be used to determine the distribution of phenotypes expected for the population of offspring. There are several situations in which the proportions of phenotypes observed in the progeny do not match the predicted values.

Epigenome Biological term

An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.

Agouti-signaling protein 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, 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.

Computational epigenetics

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.

Manel Esteller

Manel Esteller graduated in Medicine from the University of Barcelona in 1992, where he also obtained his doctorate, specializing in the molecular genetics of endometrial carcinoma, in 1996. He was an invited researcher at the School of Biological and Medical Sciences at the University of St Andrews, Scotland, during which time his research interests focused on the molecular genetics of inherited breast cancer.

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.

Transgenerational epigenetic inheritance

Transgenerational epigenetic inheritance is the transmission of epigenetic markers from one organism to the next that affects the traits of offspring without altering the primary structure of DNA —in other words, epigenetically. The less precise term "epigenetic inheritance" may cover both cell–cell and organism–organism information transfer. Although these two levels of epigenetic inheritance are equivalent in unicellular organisms, they may have distinct mechanisms and evolutionary distinctions in multicellular organisms.

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.

Epigenome-wide association study

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.

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.

Ionizing radiation can cause biological effects which are passed on to offspring through the epigenome. The effects of radiation on cells has been found to be dependent on the dosage of the radiation, the location of the cell in regards to tissue, and whether the cell is a somatic or germ line cell. Generally, ionizing radiation appears to reduce methylation of DNA in cells.

Pharmacoepigenetics is an emerging field that studies the underlying epigenetic marking patterns that lead to variation in an individual's response to medical treatment.

Manolis Kellis Greek-born computational biologist

Manolis Kellis is a professor of Computer Science at the Massachusetts Institute of Technology (MIT) in the area of Computational Biology 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.

Professor Susan J. Clark is an Australian biomedical researcher in epigenetics of development and cancer. She was elected a Fellow of the Australian Academy of Science in 2015, and is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow and Research Director and Head of Genomics and Epigenetics Division at the Garvan Institute of Medical Research. Clark developed the first method for bisulphite sequencing for DNA methylation analysis and used it to establish that the methylation machinery of mammalian cells is capable of both maintenance and de novo methylation at CpNpG sites and showed is inheritable. Clark's research has advanced understanding of the role of DNA methylation, non-coding RNA and microRNA in embryogenesis, reprogramming, stem cell development and cancer and has led to the identification of epigenomic biomarkers in cancer. Clark is a founding member of the International Human Epigenome Consortium (IHEC) and President of the Australian Epigenetics Alliance (AEpiA).

Epigenetic priming 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.

Sleep epigenetics is the field of how epigenetics affects sleep.

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. ↑ Waterland RA, Jirtle RL (2003), "Transposable elements: targets for early nutritional effects on epigenetic gene regulation", Mol Cell Biol23: 5293–5300. PMID   12861015
  12. ↑ Blakeslee, Sandra (October 7, 2003). "A Pregnant Mother's Diet May Turn the Genes Around". The New York Times.
  13. ↑ 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
  14. ↑ "Prenatal Genistein in Soy Reduces Obesity in Offspring".
  15. ↑ "Folate Shields Fetus Against Chemical in Plastics". The Washington Post . HealthDay News. July 31, 2007. Retrieved July 3, 2022.
  16. ↑ Tilson HA (2011), "EHP Classic Paper of the Year, 2011", Environ Health Perspect119: A238. PMID   21628120
  17. ↑ Dolinoy DC, Huang D, Jirtle RL (2007), "Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development", PNAS104: 13056–13061. PMID   17670942
  18. ↑ 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
  19. ↑ "Low Dose Radiation-Induced Epigenetic Alterations Found in Agouti Mouse Model". US Department of Energy. November 8, 2007. Retrieved May 23, 2013.
  20. ↑ Jirtle, RL, ed. (1995), Liver Regeneration and Carcinogenesis: Cellular and Molecular Mechanisms, San Diego: Academic Press, ISBN   012388649X
  21. ↑ Jirtle, RL; Tyson, FL, eds. (2013), Environmental Epigenomics in Health and Disease: Epigenetics and Disease Origins, Heidelberg: Springer, ISBN   978-3642233791
  22. ↑ Jirtle, RL; Tyson, FL, eds. (2013), Environmental Epigenomics in Health and Disease: Epigenetics and Complex Diseases Origins, Heidelberg: Springer, ISBN   978-3642368264
  23. ↑ "Epigenomics".
  24. ↑ "Epigenetics Editorial Board".
  25. ↑ "Environmental Epigenetics". Environmental Epigenetics Editorial Board. Archived from the original on June 13, 2015. Retrieved April 17, 2015.
  26. ↑ "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.
  27. ↑ "Person of the Year 2007". Time Magazine. November 8, 2007. Retrieved May 23, 2013.
  28. ↑ "NOVA | Ghost in Your Genes | PBS". PBS .
  29. ↑ "Article: New Epigenetic Science Award Presented in Groundbreaking Ceremony". OpEd News. Retrieved July 3, 2022.
  30. ↑ "NIH VideoCast - Epigenetics, Nutrition and Disease Susceptibility".
  31. ↑ "NIH VideoCast - Epigenetics: How Genes and Environment Interact".
  32. ↑ "Randy Jirtle, PHD, Receives Linus Pauling Award".
  33. ↑ "Are You What Your Mother Ate?". shortcutstv.com.
  34. ↑ Archived at Ghostarchive and the Wayback Machine : Epigenetic Origins of Human Health, Professor Randy Jirtle. YouTube .
  35. ↑ "2019 Thought Leaders Consortium Schedule | PLM Institute". plminstitute.org. Archived from the original on March 2, 2019.
  36. ↑ "EMGS : Blogs : EMGS is Proud to Announce the 2019 Alexander Hollaender and EMGS Award Recipients".

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