The Epigenetics Revolution: Nature, Nurture and What Lies Ahead - March 13-15, 2015

The Epigenetics Revolution:

Nature, Nurture and What Lies Ahead

March 13-15, 2015

Monsanto Auditorium

Bond Life Sciences Center

Speakers

Annie Murphy PaulAnnie Murphy Paul

A science writer and author of Origins: How the Nine Months Before Birth Shape the Rest of our Lives and the forthcoming Brilliant: The New Science of Smart. Her work has been published in the New York Times, Time.com, Slate, and MindShift.

Sharing Epigenetic Research with the Public

Friday, March 13th, 2015, 6:30 pm

In my 2010 book Origins, I wrote about epigenetic research for a broad audience—in particular, for pregnant women curious about how their own choices might affect the health and well-being of their offspring. In this talk, I will recount how I went about researching and reporting on new findings in epigenetics, how I translated these findings for a layperson readership, and how readers responded to my coverage. While I encountered great interest and excitement regarding the subject of epigenetics, I also met with less positive reactions: fear, confusion, and suspicion. I will reflect on my experiences in writing about epigenetic research for a wide audience and offer recommendations for scientists, physicians, and others who communicate with the public regarding how best to frame and explain these important findings.

Tracy BaleTracy Bale

Professor of Neuroscience and Animal Biology at the University of Pennsylvania, uses mouse models to study the development of human neuropsychiatric diseases like schizophrenia and autism.

Stress parents: maternal and paternal epigenetic programming of the developing brain

Saturday, March 14th, 2015, 9:00 am

Parental lifetime exposures to perturbations such as stress, infection, malnutrition, and to advanced age have been linked with an increased risk for neurodevelopmental disorders in their children, including autism and schizophrenia. We have developed mouse models in which we can examine how maternal or paternal stress can impact offspring brain development. In female mice, stress during a sensitive period of early pregnancy has sex-specific effects where her male offspring as adults have increased stress sensitivity. We have been able to identify specific genes in the placenta that are affected by this maternal stress and appear to impart significant changes specifically on the male fetal brain. While maternal insults during pregnancy can directly impact fetal development, the mechanisms by which paternal life experiences can also affect his offspring’s neurodevelopment are not as well understood. However, transmission of these epigenetic marks to the next generation can significantly elevate disease risk, and if programmed into the germline can affect future generations as well. By exposing male adult mice to stress and then breeding them, we also found these fathers passed on important information to their offspring by imparting effects on how their offspring react to stress as adults. In these studies, we looked at the paternal germ cells and found epigenetic marks that were changed by his stress experience. We used microinjection technology to test the importance of these marks in fertilized embryos and found that we could produce offspring with the same outcome as when the father had been stressed. These mouse models provide us with the best tools to better understand how parental experiences are able to impart changes on their future offspring’s brain, and may play an important role in disease risk or resilience.

Oliver RandoOliver Rando

Professor of Biochemistry and Molecular Pharmacology at the University of Massachusetts Medical School, uses genomic tools to study intergenerational epigenetic effects. His recent work focuses on the effect of father’s diet on offspring genes and behavior.

You Are What Your Father Ate

Saturday, March 14th, 2015, 10:30 am

The inheritance of features from parents to offspring is a fundamental feature of life. The mechanism by which biological traits are passed on to offspring was almost entirely explained with the discovery of the double helix structure of DNA. That said, not all biological inheritance is explained by DNA: every cell in one’s body carries the same DNA – the “book of instructions” – but when a liver cell divides it never makes a skin cell or a kidney cell. This inheritance of information beyond the DNA sequence is known as “epigenetic” inheritance.

Not only is epigenetic information inherited from one cell to another, but there is increasing evidence that epigenetic information gets passed from one multicellular generation to the next through the gametes – sperm and eggs. As epigenetic information can be modulated by the environment, this raises the possibility that ancestral conditions could influence future generations. This idea, often known as “the inheritance of acquired characters,” is experiencing a resurgence in modern biology due to our increasing understanding of epigenetics.

My lab and several others have used paternal exposure experiments to show that a father’s access to food can alter metabolism in his children and grandchildren. These rodent studies, along with human epidemiological studies, link ancestral nutritional status to metabolic disease in later generations. I will broadly discuss these experiments, and will discuss our efforts to understand the molecular mechanisms responsible for ancestral control of health and disease.

Massimo PigliucciMassimo Pigliucci

Professor of Philosophy at the City University of New York, is a philosopher of science and science communicator who holds no less than three doctorates. He is the author of numerous books, including Making Sense of Evolution and Answers for Aristotle, and is interested in the implications of epigenetics for evolutionary theory.

Epigenetic inheritance and evolutionary theory: the resurgence of natural philosophy

Saturday, March 14th, 2015, 11:30 am

Recent debates between proponents of the Modern Synthesis (essentially, the standard model in evolutionary biology) and those of a possible Extended Synthesis are a good example of the fascinating tangle among empirical, theoretical, and conceptual or philosophical matters that is the practice of contemporary evolutionary biology. In this talk I will explore the specific case of discussions about epigenetic inheritance as an example of how science and philosophy meet on common ground to reforge a hybrid approach to understanding complex questions, yielding something similar to what used to be called natural philosophy. A major goal of evolutionary theory is to explain adaptation, and naturalists have explained the apparent end-directedness of biological traits (e.g., eyes are “for” seeing) using two theories: Darwinism and Lamarckism. Historically, these two options have been viewed as mutually exclusive and jointly exhaustive: those who reject one are therefore committed to the other, or vice versa. But recent theoretical and empirical advances in the field of epigenetics have reopened the debate, in the process leading to much conceptual confusion and the quick establishment of entrenched positions from which dialogue seems hard to pursue. But progress is feasible, via what philosopher Roberto Mangabeira Unger and physicist Lee Smolin — in a different context — have recently referred to as modern natural philosophy. This is a discipline, or an approach, at the interface between philosophy and science but distinct from both science itself and philosophy of science. Natural philosophers are free to advance discourse in a more speculative and yet empirically coherent manner, preparing the terrain for when the new ideas are either rejected or become incorporated in mainstream science.

Irva Hertz-PicciottoIrva Hertz-Picciotto

Professor of Public Health Sciences at the UC Davis, is an environmental epidemiologist focusing on the effects of environmental toxins on human disease. Her recent work as Director of the CHARGE and MARBLES studies focuses on environmental factors that may contribute to the development of autism.

Environment and Autism: Past Evidence, Current Research and Future Quandaries

Saturday, March 14th, 2015, 2:15 pm

By the end of the 20th century, we had three main clues about the causes for autism: 1) it tended to run in families; 2) children with congenital rubella had a high rate of autistic symptoms; and 3) so did children exposed prenatally to thalidomide. These facts suggested that both genetic and environmental influences likely played a role, and that the non-heritable causes might include both microbiologic and pharmacologic agents. Since then, environmental epidemiology has produced many more leads related to potentially modifiable risk factors, ranging from an array of xenobiotic chemicals in ambient air and household products, to nutritional factors operating primarily in the periconception, to paternal or maternal aging, and several maternal acute or chronic conditions that may alter the intrauterine environment. To date, prenatal insults appear to play a particularly strong role, but postnatal influences are not ruled out. Additionally, numerous lines of research have begun to identify scaffolding themes, including immunologic dysregulation, epigenetic changes, genetic instability, or an altered hormonal milieu. At present, very little effort has gone towards understanding gene-by-environment interactions. This presentation will provide an overview of the field, highlighting studies being conducted at the UC Davis MIND Institute, key gaps, persistent myths, and enigmas to be solved.

Shanna SwanShanna Swan

Professor of Preventive Medicine at Mount Sinai School of Medicine, is a developmental epidemiologist studying the impact of environmental exposures to common chemicals in cosmetics and personal care products on male and female reproductive health. Her research played an important role in the ban on phthalates in children’s toys by the Consumer Protection Act of 2008.

Prenatal stress modifies the impact of phthalates on boys’ reproductive tract development

Saturday, March 14th, 2015, 3:15 pm

The term “endocrine disruption” is used to describe chemicals capable of interfering with the body’s endocrine system and producing adverse developmental, reproductive, neurological, and immune effects. Phthalates, man-made chemicals commonly used as a plasticizer and found in food and many household products is a class of well-studied EDCs; some phthalates reduce testosterone levels in the developing fetus. We found that non-chemical exposures can also interfere with the body’s endocrine system and produce adverse health effects. I will illustrate this concept using data from two large ongoing studies of pregnant women and their offspring that we have been conducting since 2000. We collected women’s urine and questionnaires in the first trimester to measure their exposure to phthalates and stressful life events. At birth we examined the infants and collected data on an important measure of sexual development that is typically 50%-100% longer in boys than girls, the anogenital distance (AGD). We found that when the mother had higher exposure to some phthalates in early pregnancy her boy had a shorter (less masculine) AGD, while the girls were unaffected. We then examined the number of major life events (like death, divorce, job change) in combination with phthalate exposure and found that this association in boys was much stronger among women who did not report experiencing these stressors. These data suggest that the concept of endocrine disruption be expanded to include nonchemical agents.

Shuk-mei HoShuk-mei Ho

Director of the University of Cincinnati Cancer Center and Chair of the Department of Environmental Health, studies the epigenetic effects of environmental exposure to Endocrine Disrupting Chemicals and their implications for the development and treatment of cancer.

DOHaD, Epigenetics and Cancer

Sunday, March 15th, 2015, 9:00 am

(co-authors Yuet-Kin Leung, Vinothini Janakiram, Ana Cheong, Sarah To, Pheruza Tarapore)

Some of the common characteristics of cancer cells include their ability to grow uncontrollably, evade apoptosis, elevate metabolism, escape immune-surveillance, and migrate to distant organ sites. Functional failure of multiple organs with the metastatic cancers is often the cause of death of patients. The cancerous phenotypes are driven by aberrant patterns of gene expression associated with chromosomal reshuffling and accumulation of mutations and epimutations. According to the developmental origins of health and disease (DOHaD) hypothesis some cancers may have early life origins. It is envisioned that less than optimal support mechanisms for early-life development or exposure to disruptive agents during critical developmental periods can change the course of gene expression patterns in multiple tissues later in life rendering them more susceptible to carcinogenic insults. One mechanism that mediates the reprogramming events is related to alterations in the epigenome(s) of progenitor cells. In this presentation we will provide examples in DOHaD models of prostate, breast and uterine cancer. In addition to addressing prenatal or perinatal periods as windows of susceptibility we will advocate the need to investigate other windows such as preconception; perinatal, peripubertal and pubertal periods; pregnancy; and aging. The provocative hypothesis of epigenetic drift contributing to age-related carcinogenesis will also be discussed.

Joya ChandraJoya Chandra

Associate Professor of Pediatrics at the The University of Texas MD Anderson Cancer Center, studies oxidative stress mechanisms in cancer cells to develop therapies for childhood cancer, especially leukemia.

The epigenetics of pediatric cancers

Sunday, March 15th, 2015, 10:30 am

The field of epigenetics in cancer biology and therapy is rapidly evolving and has high relevance to pediatric oncology. For pediatric cancers, new insights have been afforded by developments in understanding epigenetic enzymes. For years it has been accepted that pediatric tumors are unique in incidence, in biology and have different treatment responses than corresponding adult tumors. Now, some of these distinct attributes of pediatric cancers relative to adult counterparts are being correlated to differences in activity, expression or mutation of the enzymes that add, subtract, or recognize epigenetic modifications.

Leukemia is the most common type of pediatric cancer, unlike in adults where acute leukemia is the sixth most common cancer. In addition to differences in incidence, molecular epigenetic features distinguish acute leukemia in children. For example, 70% of infant leukemia cases display a chromosomal alteration involving the mixed lineage leukemia (MLL) gene, which is an epigenetic writer, adding specific chemical modifications to histone proteins that package DNA.

In children, brain tumors are the deadliest type of cancer. Glioblastoma is a type of brain tumor that is seen in both adults and in children, however the region of the brain where the glioblastoma arises is frequently different in younger versus older patients. Large scale DNA sequencing efforts of these tumors has revealed that mutant histone proteins are present in over 60% of pediatric glioblastoma cases. These mutant histones interact with epigenetic enzymes differently than normal histone proteins, and are an example of how the epigenetics of pediatric tumors are distinctive.

Now that some key differences between adult and pediatric tumors are being uncovered, efforts to translate this information into better therapies are emerging. Advances in drug development based on protein structure and function is enabling new medicines to enter clinical trials, providing hope for some of the worst types of pediatric cancers.

Ted KoditschekTed Koditschek

Professor of History at the University of Missouri, is an expert on 19th century British class and imperialism whose current research focuses on the development of social evolutionary thought, including the history and influence of the Lamarckian concept of the inheritance of acquired characteristics.

Before Epigenetics: Early Ideas about the Inheritance of Acquired Characteristics

Sunday, March 15th, 2015, 11:30 am

This presentation will examine early ideas about the inheritance of acquired characteristics, primarily as these ideas developed and declined during the nineteenth and early twentieth centuries. The goal will be to understand why these ideas were initially embraced, and why they were ultimately discarded. Analysis will focus on explanations that were internal to the logic of scientific discovery, as well as external forces that were influencing science through factors at work in society. My analysis will focus specifically on 1) The theory of J.B. Lamarck and his radical followers during the early nineteenth century. 2) Herbert Spencer, a late nineteenth century ‘progressive’ bio-social theorist who mounted a spirited defense of these ideas when they were coming under attack, especially from the work of August Weismann. 3) The early twentieth century, when the triumph of Mendelian genetics in biology discredited ideas about the inheritance of acquired characteristics. At the same time, many of the legacies of Lamarck and Spencer were taken up by social scientists operating in non-biological disciplines and theoretical frameworks. The presentation will conclude with some brief reflections on the response of social scientists to the return of epigenetic approaches in biology. I will also briefly reflect on some ways in which contemporary epigenetics may be similar to and/or different from the initial ideas about the inheritance of acquired characteristics.

Affiliated Events Speakers

Karthik PanchanathanKarthik Panchanathan

Assistant Professor of Anthropology, University of Missouri

Genes, culture, and evolution

Monday, March 9th, 2015, 1:00 pm

Ellis Library Government Documents Section

Epigenetics refers to the study of traits that are heritable but not caused by changes in the DNA sequence. And, in some cases, events that happen during an individual’s life can sometimes result in epigenetic changes that are subsequently heritable. This is a form of Lamarckian inheritance, the idea that an organism can pass on characteristics that it acquired during its lifetime to its offspring. Humans are unique among animals in the degree to which adaptive behavior is shaped by both genes and culture. Cultural transmission is a form of Lamarckian inheritance: individuals pass on cultural traits which they learned during their lifetime to their offspring. In this talk, I’ll discuss how anthropologists think about and model cultural evolution. In particular, I’ll discuss how and why natural selection on genes resulted in the human capacity for culture; how cultural evolution is similar to and different from genetic evolution; and how cultural processes have shaped our genes, so-called gene-culture co-evolution.

Sir Michael RutterSir Michael Rutter

Professor of Developmental Psychology, Institute of Psychiatry, King’s College, London

Professor Sir Michael Rutter has been described as the most illustrious and influential psychiatric scientist of his generation. His career has spanned more than five decades and is marked by a remarkable body of high-impact research and landmark studies. He has published around 500 scientific papers, and over 50 books. The theme running through all his work has been child development, on the subtle interplay between nature and nurture and on the factors that make the difference between a child flourishing, or floundering. Professor Rutter became the first UK Professor of Child Psychiatry, and is widely credited with founding the field of child psychiatry. He set up the Maudsley Research Center’s Child Psychiatry Research Unit and the Social, Genetic and Developmental Psychiatry Centre at King’s College in London, where he is currently Professor of Developmental Psychopathology. He is a Fellow of the Royal Society and a Founding Fellow of the Academia Europaea and the Academy of Medical Sciences.

Profound Global Institutional Deprivation: The Example of the English and the Romanian Adoptee Study

Tuesday, March 17th, 2015, 3:30 pm

Jesse Wrench Auditorium

This talk will focus on the English and Romanian Adoptee (ERA) project, a longitudinal, multi-method investigation of the development of a random sample of 165 Romanian children, most of whom spent their early lives in severely deprived institutional settings, and were then adopted (before age 3 ½ yrs) into generally well-functioning English families; 52 adopted children from the UK who had not lived in institutions served as a control group. Although most children experienced huge improvements in psychological functioning following successful adoption, a substantial minority adopted after 6 months of age continued to experience significant problems (relative to the UK controls), including autistic-like qualities, problems with forming appropriate attachments and social functioning, inattention, overactivity, and poor mental functioning. Follow-ups at 15 years of age revealed deficits and problems that appear to be deprivation-specific, and underscore the importance of early childhood environments.

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