Category Archives: Epigenetics

Description

The Center for Genomics and Systems Biology (CGSB) at New York University Abu Dhabi (NYUAD) invites applications from individuals to be appointed as a Postdoctoral Associate. The position will be based at NYU Abu Dhabi and supervised by Dr. Kirsten Sadler Edepli.

The Postdoctoral Associate will use bioinformatics tools applied to genomics datasets and experimental approaches to study regeneration, development, or other biological processes. Projects in the Edepli lab integrate datasets from model organisms (mice and zebrafish) to understand how altering the epigenetic landscape promotes or restricts liver regeneration in mice.

Applicants must have a PhD in biological sciences, genetics, genomics, cell biology, physiology, or related fields. Applicants who have sold expertise in epigenetics, epigenomics, and multi-omics and who seek to join a dynamic and creative team of scientists focused on the epigenetic mechanisms regulating regeneration across diverse species will be considered.

The terms of employment include highly competitive salary, housing allowance, and other benefits. Applications are accepted immediately and candidates will be considered until the position is filled. To be considered, all applicants must submit a cover letter, curriculum vitae, transcript of degree, a one-page summary of research accomplishments and interests, and at least 2 letters of recommendation, all in PDF format. If you have any questions, please email:nyuad.cgsb@nyu.edu

About NYUAD:

NYU Abu Dhabi is a degree-granting research university with a fully integrated liberal arts and science undergraduate program in the Arts, Sciences, Social Sciences, Humanities, and Engineering. NYU Abu Dhabi, NYU New York, and NYU Shanghai, form the backbone of NYUs global network university, an interconnected network of portal campuses and academic centers across six continents that enable seamless international mobility of students and faculty in their pursuit of academic and scholarly activity. This global university represents a transformative shift in higher education, one in which the intellectual and creative endeavors of academia are shaped and examined through an international and multicultural perspective. As a major intellectual hub at the crossroads of the Arab world, NYUAD serves as a center for scholarly thought, advanced research, knowledge creation, and sharing, through its academic, research, and creative activities.

EOE/AA/Minorities/Females/Vet/Disabled/Sexual Orientation/Gender Identity Employer

UAE Nationals are encouraged to apply.

Equal Employment Opportunity Statement

For people in the EU, click here for information on your privacy rights under GDPR:www.nyu.edu/it/gdpr

NYU is an equal opportunity employer committed to equity, diversity, and social inclusion.

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Post-Doctoral Associate in the Center for Genomics and Systems Biology job with NEW YORK UNIVERSITY ABU DHABI | 291713 - Times Higher Education

IN AN ARTICLE entitled How to Have the Best Pregnancy Ever, published in 2013 on the feminist news site Jezebel, Tracie Egan Morrissey offers advice to her readers. Doctors say that a glass of wine a day will not harm your unborn baby, or its IQ, she writes, referring to a study in the British Journal of Obstetrics and Gyncology. That being said, Morrissey continues, citing an article in PLOS ONE, even one glass of wine in your entire pregnancy could lower your babys IQ. What follows is a gleeful onslaught of contradictory and sometimes absurd guidance, much of it supported by peer-reviewed research. Dont eat fatty foods! Dont sleep on your back! Rub almond oil all over your taint! The drumbeat of directives and prohibitions will be familiar to any reader who has ever been pregnant. So might the ability of that drumbeat to keep the pregnant person on high alert. In 2022, it goes almost without saying that injunctions and warnings of this kind take aim at one party: the womb-bearing parent.

In a world where the CDC recommends that all women of childbearing age take birth control or abstain from drinking on the off chance that they might become pregnant, it may be difficult to imagine that the gestating parent wasnt always on the hook for the quality of the baby. To the contrary: Fathers, genetic chance, and the child-rearing environment each took a star turn. As historian and philosopher of science Sarah S. Richardson writes in The Maternal Imprint: The Contested Science of Maternal-Fetal Effects, the very idea that the parent contributing the egg plays an equal role in heredity to the parent contributing the sperm was radical, constituting something of a revolution on the scientific front and in ideas about gender. In the 1880s, German biologist August Weismann demonstrated that eggs and sperm contain equal quantities of hereditary material. He also showed that this material doesnt change as a result of its carriers life experiences. Before then, however, educated thinkers of all stripes believed that egg-bearers and sperm-bearers brought qualitatively and quantitatively different elements to shaping offspring. They also thought that what happened to prospective parents in the course of their lives could affect the hereditary material they passed to their offspring. According to Descartes, for example, mothers had nothing to do with a fetuss internal organs. Rather, they telegraphed through the umbilical cord what its body ought to look like. And either parent leading a dissipated life would, in the view of some 19th- and early 20th-century physicians, impart deficits to an embryo at conception. Physician and eugenicist Frederick Walker Mott railed especially at the race poisons, alcohol and syphilis, which could make sperm degenerate.

These ideas werent merely the result of technical constraints on what scientists could see and describe. Researchers enlisted evidence at the cellular level to support the story of separate reproductive roles for males and females. Biologists who observed sperm under a microscope concluded that the heroic, wriggling gametes rejuvenated eggs, infusing the lineage with vim and vigor. Even granting that eggs and sperm contributed the same amount of hereditary material, some researchers, like American zoologist William Keith Brooks, maintained that the egg carried instructions for a general species type what makes a fetus recognizable as, say, a human while the sperm contained the blueprint for a unique individual. Scottish biologists Patrick Geddes and J. Arthur Thomson took the division of labor further: ova were responsible for passive maintenance, they insisted, while sperm built and synthesized. Eggs, in effect, furnished raw material, while sperm served as both the architectural visionaries and the contractors realizing the vision. In all these accounts, whatever genius a child might possess is clearly derived from the male parent.

This is not to say that mothers were ever in the clear, particularly with respect to damaging a fetus. Even when Weismanns theory of sex equality in heredity was ascendant, many respected researchers, clinicians, and members of the public continued to understand the bodies of pregnant women as dangerously porous. Against this backdrop, the idea that women could influence their developing fetuses for good that the behaviors and attitudes of gestating parents could make children healthy, pious, and intelligent was hailed by some as progressive. Eugenic thinkers of a feminist bent and their followers seized on this possibility as creating an arena where women had agency. They used claims that women could gestate an improved race to argue that women should have the freedoms and resources to realize that potential.

If youre detecting a war of the sexes coursing through debates about how heredity works, youre not wrong. Gender politics, Richardson makes clear, at once spring from and are embedded in European and American theories of heredity. Late 19th- and early 20th-century thinkers wrote frankly about the premise that, on the cellular stage, the relationship between eggs and sperm played out the balance of power between the sexes. On the side of Weismann and the androgynous germ plasm, philosophical thinkers like Simone de Beauvoir cited equality in gametes as proof that the sexes themselves had to be equal in some fundamental way. Disciples of complementarity theories of egg and sperm, meanwhile, saw reflected under their microscopes the self-evident truth that males were active and original, igniting creation and driving innovation, while females were passive and inertial, warehousing nourishment and conserving traits through time.

Like other scientific theories, ideas about how parents influence their unborn children did not and do not emerge out of social vacuums. Richardson is the latest in a series of thinkers, including anthropologist Emily Martin, to identify how theories of heredity locate intuitions about causality in authoritative knowledge, however it might be defined in a particular time and place. That is to say, if an account feels true if so-called common sense suggests that it is true then it can be difficult for empirical evidence to dislodge the master narrative it is enlisted to support, whether with regard to the formation of a blastocyst or the readout from a PCR. The scientific and medical workers in Maternal Imprint were steeped in such master narratives. They appealed to and drew from the microscope and from the observations and lived experiences of everyday people. And their spheres of influence extended beyond the learned community and into Chautauqua tents, popular pamphlets, and amphitheaters, sometimes creating echo chambers in which popular belief and quantitative data reinforced one another.

Its well and good to call out logical fallacies and wishful interpretations of data in disciplines that have long since lost scientific legitimacy phrenology and eugenics, for instance. But the stakes are much higher when critics of science identify suspect master narratives at work in fields that are cutting-edge today. At the heart of Richardsons book is just such a critique of the burgeoning world of epigenetics. Epigenetics, the field of biology concerned with how DNA is expressed or silenced, has been welcomed as emancipating us from the tyranny of genetics our fate is no longer carved in stone in our genes and as a call to personal responsibility. As the CDC website on epigenetics puts it, Since your environment and behaviors, such as diet and exercise, can result in epigenetic changes, it is easy to see the connection between your genes and your behaviors and environment. Statements like these make the relationship between environment, behavior, and epigenetic change sound straightforward. Richardson takes on three prominent case studies in epigenetics to demonstrate that it is anything but.

Each case takes as its departure point a stressor a stimulus with the potential to knock a body out of biological equilibrium experienced by women of childbearing age. In two scenarios, the Dutch famine winter of 19441945 and the 1998 ice storm in the Montrgie region of Quebec, researchers focus on pregnancies that took place during or shortly after an acute challenge. They believe that gestating parents bodily experiences, like hunger and cold, and their psychological experiences, like anger and fear, leave epigenetic traces on the genomes of their children. The third case study, led by neurogeneticist Rachel Yehuda, seeks to explain through epigenetics how high cortisol levels in Holocaust survivors correlate with relatively low cortisol levels in their children. All three studies claim to have discovered an effect of the stressor on gene expression patterns in offspring. They also assert that these epigenetic changes cause deficits, including higher body mass indices among children gestated during the Dutch famine and the Quebecois ice storm and attenuated stress responses among the children of Holocaust survivors.

How big are these changes, and how worried should prospective parents be? (It would seem that our pregnant Jezebel readers now have epigenetics to add to the list of threats!)

Richardson points to major grounds for caution when interpreting the results of epigenetic studies. The first red flag is that the effects identified are subclinical, meaning that they wouldnt register at a doctors visit where a care provider is looking for signs that somethings wrong. Richardson refers to such effects as cryptic. By contrast, she notes, Previous eras of research [] focused on severe, gross prenatal deprivations causing visible, macroscopic outcomes. While research in the past was concerned with issues like folate deficiency causing spina bifida or thalidomide getting in the way of fetal limb formation, the biological traces of epigenetic difference arent at all obvious.

Setting aside health effects, the epigenetic changes measured in humans often fall well below the threshold of what scientists consider worth talking about in animal research. Studies of epigenetic changes in rats and mice show methylation levels, a metric of epigenetic change, between 20 and 100 percent at the locus of interest. Significant epigenetic changes like these do result in readily detectable changes in offspring bodies and behavior, whether it is in fur color or response to novel environments. Human studies, on the other hand, often report methylation differences under 10 percent.

The concerns pile on. Most researchers dont look at the entire epigenome, instead zeroing in on portions contained in pre-designed and commercially available chips, so the range of changes that might turn up in a study is limited from the outset. Epigenetic changes are measured in tissue, and it happens to matter what tissue you choose for measurement, since methylation patterns differ across the blood, skin, and internal organs within each person. Even a single tissue, like blood, contains many types of cells carrying information from all over the body. Their epigenetic signals might be responding to circumstances far removed from, say, a trauma experienced in utero. In fact, methylation patterns at some sites change on time scales ranging from hours to years. Not only is the tissue itself important, but it matters when in the life course you collect it if you dont get a sample at birth, its possible that the changes you observe took place at a later time and werent caused by experiences during gestation.

Then there are all the possible explanations for epigenetic differences that studies dont consider. Genes and epigenetics arent unrelated; your genes have a lot to say about your methylation patterns, so it may be that your biological family has more impact on your epigenetic profile than your lived experience. This is particularly noteworthy because studies focus almost exclusively on gestating parents, meaning that genetic, epigenetic, behavioral, and psychological data from the sperm-contributing parent are missing. And, as in all studies of variation, sample size matters. The smaller the data set, the more influence any single data point has on the story you tell.

People are invested in epigenetic narratives, just as they were invested in the self-evident truths of phrenology and the aspirational rallying cries of eugenics. And for good reason. Biological evidence, carrying with it deep forms of authority, confers legitimacy on experience: if its in the genes, it really happened. Recently, I described Richardsons doubts about the epigenetics of Holocaust survival to a colleague. He had heard Yehuda speak some years prior. His mother-in-law, he explained, was a Holocaust survivor, and the description Yehuda offered of the psychology of survivors mapped perfectly onto his own familys lived experience. The framework Yehuda proposed to explain the transmission of trauma across generations offered him and his wife a profound sense of relief; the anxiety his wife carried, and the anxiety they observed in their children, now felt inevitable and thus worthy of forgiveness. It had released them from the story that their suffering resulted from bad parenting. No thoughtful or rigorous critique, he told me, with a mix of gentle humor and deep seriousness, would persuade his family to relinquish the explanatory lifeline Yehuda had thrown to them.

In this anecdote, we find the crux of the issue: stories about heredity are maps of responsibility. They can function therapeutically or punitively, attributing problems to supposedly immutable sources like biology or to theoretically flexible causes like behavior. (Neither explanation, of course, is inherently progressive just ask LGBTQ-plus rights activists about the possibilities and perils of born this way.) What they often also do, as Richardson illustrates, is stick the gestating parent with the proverbial bill. No matter that the circumstances under investigation were out of pregnant peoples control: no gestating parent could be blamed for a famine in the middle of a war, an ice storm, or attempted genocide. The pathway of action for these catastrophes, according to scientists, is the maternal body. The gestating parent, therefore, becomes the locus of surveillance and intervention, the site of infinite possibility and infinite frustration in the quest for some elusively optimal way to be.

As an anthropologist who studies reproduction, I run in circles, biological and political, with colleagues about the role of the mother in reproductive outcomes. Entire professional organizations, including the International Society for the Developmental Origins of Health and Disease, convene on the premise that the gestating body or indeed, the potentially gestating body is the place to intercede to promote the birth of healthy children who grow into productive members of society. Here, I think we could benefit from turning back to the writer of the Jezebel article, Tracie Egan Morrissey, who has wisdom to offer on the question of how much any individual can steer reproductive destiny. Dont have asthma or allergies, she writes. Dont live near pollution. [] Dont be poor.

What would it mean for theories of heredity if we were to turn away from the individual as the site of intervention and focus instead on addressing human needs to eat, have safe shelter, and be free from persecution? What if we were to create a world in which gestating did not entail a nine-month passage through an environmental minefield? Then we might put what Richardson describes as the long reach of the womb in perspective and allow the womb-equipped among us a centuries-overdue sigh of relief.

Meredith Reiches is an associate professor of Anthropology at the University of Massachusetts, Boston.

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Womb with a View: On the Science of Maternal Effects - lareviewofbooks

Technological Advancements Leading to Enhanced Efficiency & Greater Precision of Molecular Biology Enzymes, Kits & Reagents

Many technological advancements are been made by the molecular biology enzymes, kits & reagents manufacturers, who dedicate their focus toward developing advanced products in a bid to enhance their product portfolio. The advanced products facilitate the research processes with offerings such as enhanced efficiency and greater precision. One of the greatest examples of this is SMART Digest Kit developed by Thermo Fisher Scientific, Inc., designed particularly for the biopharmaceutical & proteomic applications. This kit enables the generation of data of high quality, meanwhile curtailing time needed for preparation of samples. Adoption of molecular biology enzymes, kits & reagents will further be propelled by huge investments made in the research & development by pharmaceutical & biotechnology industries coupled with the provision of several reimbursements for molecular diagnostics.

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A significant increase in the genetic disorders prevalence has been witnessed since the recent past, thereby driving adoption of molecular diagnostics. The processes of molecular diagnostics including epigenetics and polymerase chain reaction (PCR) require molecular biology enzymes, kits & reagents as, which form an integral part of these processes. Mounting cases of genetic disorders in light of growing geriatric population will significantly fuel demand for molecular biology enzymes, kits & reagents in the near future. Genetic data of individuals is considered highly confidential, and sharing this data is strictly prohibited. Genome sequencing aids identifying & treating a wide variety of diseases. However, there is lack of tools that are effective for securing the genetic information of individuals, and the information ends up being stored in cloud databases, which further poses threats regarding data thefts. The absence of effective technology to store genetic information is anticipated to negatively influence demand for molecular biology enzymes, kits & reagents.

Key Research Findings from the Report

Prominent companies in the global molecular biology enzymes, kits & reagents market are implementing strategies including manufacturing capacity & geographic expansion. Manufacturers are also concentrating on new product launches for enhancing their shares in this increasingly competitive market. The report has listed key players supporting the market growth, which include Thermo Fisher Scientific Inc., Illumina, Inc., Roche Holdings, Inc., Takara Bio Inc., Jena Bioscience GmbH, Merck & Co Company, Qiagen N.V., Agilent Technologies, Inc., KRISHGEN BioSystems, and Promega Corporation.

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Market Taxonomy

A segmentation analysis offered in the report propounds forecasts on global molecular biology enzymes, kits & reagents market. Categorizing the market in terms of application, end-user, product type, and region. Analysis on Y-o-Y growth comparison, the market share comparison, and the revenue comparison coupled with relevant market numbers is offered in this chapter. Global market for molecular biology enzymes, kits & reagents has been regionally divided into Japan, Middle East & Africa, Europe, Asia-Pacific excluding Japan, North America, and Latin America.

Region

Product Type

End User

Application

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Molecular Biology Enzymes, Kits & Reagents Market likely to bring in approximately US$ 22000 Million revenues by 2026-end Political Beef -...

MADISON, Wis. (AP) New data shows a sharp increase in Type 2 diabetes among children in Wisconsin and doctors think COVID-19 could be a factor.

Figures from UW Health Kids shows a nearly 200% increase in the number of cases over the last several years.

Dr. Elizabeth Mann is a pediatric endocrinologist and director of the Type 2 Diabetes Program at UW Health Kids. Mann says its a trend medical experts have noticed for years, but its taken a worrisome turn recently.

Since the beginning of the pandemic, weve just seen a sharp increase beyond what we had expected, Mann said.

In 2018, 5.8% percent of pediatric patients with new onset diabetes at Madisons American Family Childrens Hospital had Type 2, a disease that primarily affects adults. In 2021, that number grew to 16.4%. And so far in 2022, 1 in 6 pediatric patients at the childrens hospital with new onset diabetes has Type 2, Wisconsin Public Radio reported.

In kids, this Type 2 diabetes just acts a little bit more aggressively, Mann said. So its not only that were seeing Type 2 diabetes at younger ages, but it also seems to be a more severe form where kids are needing more medications and have more significant complications from it.

In Type 2 diabetes, the most prevalent form overall, the pancreas produces insulin but the body has developed a resistance to it.

Mann said there is a common misconception that Type 2 diabetes is purely a result of diet and activity levels. She said genetics and epigenetics play a big role in making people more susceptible to the disease.

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Type 2 diabetes on the rise among Wisconsin children - Iron Mountain Daily News

This month marks the first anniversary of the Directors Corner, which I launched to share innovative ideas and promote collaboration across the environmental health sciences community. I recently spoke with NIEHS grantee Cathrine Hoyo, Ph.D., from North Carolina State University (NC State), who conducts research that is both innovative and collaborative, and I think that our conversation provides the perfect segue into the new year.

Hoyo aims to shed light on how early environmental exposures affect humans later in life. She designs rigorous epidemiological studies involving diverse populations and toxic agents of great public health significance, and her efforts are informed by epigenetic analysis. Epigenetics refers to chemical modifications on DNA or the proteins associated with DNA that affect how genes are turned on and off. Hoyo seeks to boost knowledge about conditions such as obesity and liver dysfunction by identifying epigenetic changes that are caused by developmental exposure to cadmium, per- and polyfluoroalkyl substances (PFAS), and other contaminants.

Through that research, she advances a framework known as developmental origins of health and disease (DOHaD) and uncovers how African Americans may be disproportionately affected by certain exposures. A native of Zimbabwe, Hoyo is a Distinguished Professor at NC State, where she leads the Epigenetics, Cancer, and the Environment Laboratory. She also is co-director of the Integrative Health Science Facility Core in the universitys NIEHS-funded Center for Human Health and the Environment (CHHE).

Rick Woychik: You are spearheading the Southern Liver Health Cohort, a major new project funded by NIEHS and the National Cancer Institute. The aim is to increase understanding about which environmental contaminants may be linked to liver cancer and its precursors, including fibrosis, in an ethnically diverse population of 16,000 men and women. Can you share with our readers the impetus for this initiative, and what specifically do you hope to learn?

Cathrine Hoyo: Sure. We are part of five teams that are developing new cohorts that will help to advance basic research across the country. Our group is looking at both heavy metals and PFAS, and we will collect blood, urine, and tissue samples from a diverse adult population and follow those individuals over time. The goal is to see who develops nonalcoholic fatty liver disease, how that may progress to fibrosis, and how that in turn may lead to liver cancer.

One reason I wanted to be part of this project is because of my previous research involving the NIEHS-funded Newborn Epigenetics Study Cohort(https://tools.niehs.nih.gov/cohorts/index.cfm/main/detail/ids/c178). As part of that ongoing effort, we studied a group of women in Durham, North Carolina, to learn how environmental stress cadmium exposure around the time of pregnancy influenced health outcomes in their children.

We found that 10% of African American children had nonalcoholic fatty liver disease by age 10 an alarming percentage, and one that was significantly higher than what we saw in other children. Our group would not have discovered that if the cohort was not ethnically diverse, and I think that such diversity will be a major benefit to the Southern Liver initiative, too.

When we look at the incidence of liver cancer, we see that the steepest increases in the last 15-20 years are in the southeastern and southwestern United States. We want to learn why that is so, and I think that through further study of the cohort of children and now the Southern Liver project, we are positioned to do exactly that.

RW: What inspired you to study DOHaD and to merge insights from the field of epigenetics?

CH: Back in the early 2000s, I was at Duke University, in the lab of Randy Jirtle. He had followed up with your experiments involving the agouti gene and published a seminal paper demonstrating that certain nutritional exposures experienced on the maternal side can lead to potentially harmful epigenetic modifications that affect offspring. I was and still am interested in how the environment can affect gene expression and ultimately influence metabolic dysfunction, including obesity, so his work has been a major source of intellectual inspiration.

In my early studies, I focused on an imprinted gene called insulin-like growth factor 2 [IGF2], which regulates the bodys growth hormone. Expression of an imprinted gene is determined by the parent who contributed it, and such expression is based on epigenetic modifications in the germline, meaning sperm and egg cells. Loss of imprinting in IGF2 is linked to conditions such as diabetes and cardiovascular disease, and it can predispose some individuals to obesity.

RW: What came after that research?

CH: I wanted to identify a broad set of imprinted genes that would help us better assess the mechanisms through which exposures perturb gene expression and affect obesity. For epidemiologists, having a repertoire of these genes would be a gold mine because we know when epigenetic marks are established in them. We would be able to determine when and how an exposure causes loss of imprinting.

Such a robust set of genes would allow us to evaluate the effects of exposures that occur very early in life, even when the woman does not yet know she is pregnant. That knowledge could aid disease prevention efforts and lead to therapeutic advances.

So, that started me along the path of first looking at known imprinted regions, and I published a related paper in 2012 with my colleague David Skaar. Around that time, I was studying imprinted genes in relation to cadmium because I found a cluster of individuals in Durham County who had been exposed to the metal. I developed cohort studies examining exposures in very early pregnancy, trying to analyze resulting epigenetic changes.

However, that proved inefficient, so we did whole genome analyses to see which imprinted regions would truly shed light on the early-life epigenetic consequences of exposure to cadmium and other heavy metals. We discovered that some regions were more useful for this kind of research than others, and we published our findings in the journal Environmental Health Perspectives.

Eventually, I collaborated with a bioinformatician from [CHHE] to take a deeper dive into these imprinted genes. We have discovered more than 300 regions that we think hold promise in terms of helping scientists understand the epigenetic effects of exposures, and our findings will be published soon.

Also, we are working with the biotech company Illumina to develop a platform based on these imprinted regions that allows other researchers to study more exposures and diseases through an epigenetic lens. I am quite excited about what the future holds.

RW: That sounds fascinating, and I think your efforts will enable scientific breakthroughs in the coming years. You mentioned CHHE. Can you talk about your involvement with the center?

CH: Yes, absolutely. This NIEHS-funded center has provided me and other researchers with more opportunities for partnership, and for that I am grateful. The center has a full-time bioinformatician who can work in a variety of models, whether involving zebrafish, mice, or human epidemiological studies.

There is an interdisciplinary element that also is unique, in my view. We have more than 70 investigators from across a variety of departments at NC State, and researchers often collaborate with scientists from nearby universities.

Also, the center offers state-of-the-art equipment and funding that enable me to conduct studies that I otherwise would be unable to even think about [laughs].

For example, the Southern Liver Health Cohort started as a $50,000 pilot project. Half of that amount came from [CHHE], and the other half came from the UNC [University of North Carolina at Chapel Hill] Center for Environmental Health and Susceptibility, which also is funded by NIEHS. It has been exciting to watch the study blossom into something much more comprehensive.

Citations:House JS, Hall J, Park SS, Planchart A, Money E, Maguire RL, Huang Z, Mattingly CJ, Skaar D, Tzeng JY, Darrah TH, Vengosh A, Murphy SK, Jirtle RL, Hoyo C. 2019. Cadmium exposure and MEG3 methylation differences between Whites and African Americans in the NEST Cohort. Environ Epigenet 5(3):dvz014.

Bultman SJ, Michaud EJ, Woychik RP. 1992. Molecular characterization of the mouse agouti locus. Cell 71(7):1195204.

Michaud EJ, van Vugt MJ, Bultman SJ, Sweet HO, Davisson MT, Woychik RP. 1994. Differential expression of a new dominant agouti allele (Aiapy) is correlated with methylation state and is influenced by parental lineage. Genes Dev 8(12):146372.

Waterland RA, Jirtle RL. 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23(15):5293300.

Do EK, Zucker NL, Huang ZY, Schechter JC, Kollins SH, Maguire RL, Murphy SK, Hoyo C, Fuemmeler BF. 2019. Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children. Pediatr Obes 14(2):e12454.

Skaar DA, Li Y, Bernal AJ, Hoyo C, Murphy SK, Jirtle RL. 2012. The human imprintome: regulatory mechanisms, methods of ascertainment, and roles in disease susceptibility. ILAR J 53(3-4):34158.

King KE, Darrah TH, Money E, Meentemeyer R, Maguire RL, Nye MD, Michener L, Murtha AP, Jirtle R, Murphy SK, Mendez MA, Robarge W, Vengosh A, Hoyo C. 2015. Geographic clustering of elevated blood heavy metal levels in pregnant women. BMC Public Health 15:1035.

Cowley M, Skaar DA, Jima DD, Maguire RL, Hudson KM, Park SS, Sorrow P, Hoyo C. 2018. Effects of cadmium exposure on DNA methylation at imprinting control regions and genome-wide in mothers and newborn children. Environ Health Perspect 126(3):037003.

(Rick Woychik, Ph.D., directs NIEHS and the National Toxicology Program.)

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January 2022: Exposures, diverse populations, and epigenetics merge in grantee's lab - Environmental Factor Newsletter

Not surprisingly, theres still plenty of interesting research coming out about COVID-19, but the end of 2021 also provided exciting science in other areas. Heres a look.

Scientists out ofWashington University School of Medicinewanted to understandwhy the mRNA vaccines by Pfizer-BioNTech and Moderna are so effective at preventing severe disease. Even in the face of Omicron, which is particularly good at evading immune protection, people vaccinated with the two mRNA vaccines appear to be strongly protected against hospitalization and death from COVID-19. The researchers, along withSt. Jude Childrens Research Hospital,found that the Pfizer-BioNTech strongly and persistently activated a specific type of helper immune cell known as T follicular helper cells. These immune cells help antibody-producing cells to create large amounts of increasingly powerful antibodies and drives development of some forms of immune memory. They published their research in the journalCell.

The longer the T follicular helper cells provide help, the better the antibodies are and the more likely you are to have a good memory response, said Dr. Philip Mudd, co-corresponding author and assistant professor of emergency medicine at Washington University. In this study, we found that these T follicular helper cell responses just keep going and going. And whats more, some of them are responding to one part of the viruss spike protein that has very little variation in it. With the variants, especially Delta and now Omicron, weve been seeing some breakthrough infections, but the vaccines have held up very nicely in terms of preventing severe disease and death. I think this strong T follicular helper response is part of the reason why the mRNA vaccines continue to be so protective.

Generally, the first antibodies generated in response to an infection or vaccine arent very high quality. The researchers say B cells need to go through a sort of boot camp in the lymph nodes before they can generate very powerful antibodies. T follicular helper cells, they note, are the drill sergeants of the boot camps. The helper cells give instructions to the antibody-producing cells on how to make even better antibodies and then encourage the best to multiple and sometimes become long-lived memory B cells.

More Data Omicron Evades Immune Protection

The growing body of evidence that the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, can evade immunity created with vaccines and natural infection gained yet more support. Research out ofColumbia University Irving Medical Centerand theUniversity of Hong Kongtested antibodiesgenerated by vaccination and their ability to neutralize Omicron in laboratory assays using live viruses and pseudoviruses that mimic Omicron. They found that antibodies from people double-vaccinated by the Moderna, Pfizer-BioNTech, AstraZeneca-Oxford and Johnson & Johnson vaccines were significantly less effective against Omicron compared to the wildtype Wuhan strain. And the antibodies from people who were naturally infected were even less effective. The booster shots helped, but still showed decreased neutralizing activity.

Microorganism Helps Understand Cancer Resistance

Scientists atArizona State Universitydescribethe ability of a microorganism,Trichoplax adhaerens, to repair its DNA, even from significant radiation exposure. It also can extrude injured cells, which then die. The research provides insights into natural cancer-suppression mechanisms in a wide range of lifeforms.T. adhaerensis the simplest multicellular organism on Earth and is native to the Red Sea and other warm waters. In addition, its complete genome has been sequenced. No cancer has ever been seen in the organism. They can withstand radiation by increasing the expression of particular genes involved in DNA repair and genes linked with apoptosis (cell death). Their ability to extrude damaged cells, such as precancerous cells, may also explain their ability to fend off cancer.

Epigenetics of Microglia in the Brain

Epigenetics is the study of how the environment or behaviors change the ways genes work. In other words, although genes are sometimes turned on and sometimes turned off, epigenetics is the study of what turns them on or off and any in between states. Microglia are a type of immune cell found in the brain and central nervous system. They were thought for a long time to be activated or inactivated, and their effects were either pro-inflammatory or neuroprotective. But researchers at theIcahn School of Medicine at Mount Sinai, led by Fatemeh Haghighi, Professor of Neuroscience and Psychiatry,isolatedmicroglia cells from post-mortem human brain tissue from 22 people. The patients had a variety of illnesses while alive: one with schizophrenia, 13 with mood disorders, and 8 with no psychiatric disorders. The researchers used genome-scale methylation microarrays to analyze the microglia. Methylation is one form of epigenetic control of genes. They found that microglia demonstrated DNA methylation profiles distinct from other CNS cells, which was expected. But they also found differences in the methylation levels of microglia individually, which suggested that microglial methylation may play a role in a variety of psychiatric disorders.

Antibiotic-Antioxidant Combo Slows Dementia in Mice

Dementia, such as Alzheimers, is believed to be caused by an accumulation of proteins called beta-amyloid, tau and alpha-synuclein, which collect in the brain and form oligomers. Researchers atOsaka City University Graduate School of Medicinehad previouslydescribedthe use of the antibiotic rifampicin to remove oligomers from the brain, which improved cognitive function. But rifampicin can cause liver damage and other side effects. Resveratrol is a naturally occurring plant antioxidant that is used as a supplement in the U.S. and Europe. The researchers thought they could combine the positive effects of rifampicin while fighting its negative effects with resveratrol. They used a fixed dose combination intranasally five days a week for four weeks on mice models of Alzheimers, frontotemporal dementia, and dementia with Lewy bodies. The drugs improved cognition, inhibited oligomer accumulation, and restored synaptophysin levels, which facilitate synapses. In addition, the blood levels of liver enzymes that typically increase with rifampicin stayed normal. A bonus was they observed increased levels of brain-derived neurotrophic factor (BNDF) expression in the hippocampus, which was not typically seen with only rifampicin.

Severe COVID-19 Negatively Affects B-Cell Memory

Researchers at theUniversity of Texas Health Science Centerat San Antoniofoundthat patients who recovered from less-severe cases of COVID-19 had B cells that had better immune memory of the viruss spike protein compared to patients who recovered from severe COVID-19. The researchers analyzed blood samples a month after symptom onset and five months post-onset. At the one-month mark, a significant percentage of spike-specific B cells were active. But in eight people who recovered from less-severe disease, they had increased expression of markers linked with durable B-cell memory compared to people who recovered from severe disease. The markers included T-bet and FcRL5.

The increased percentage of B cells associated with long-lived immunity in non-severe COVID-19 patients may have consequences for long-term immunity against SARS-CoV-2 re-infection or severity of the resulting disease, the authors wrote.

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Research Roundup: Why mRNA Vaccines are So Good Against Severe COVID-19 and More - BioSpace

Epigenetics is the study of changes in gene function that are heritable and that are not attributed to alterations of the DNA sequence. The term epi means above. It's a Greek prefix. It's also defined as on top of the basic DNA sequence. In general terms you can think of them like accent marks on words where the DNA is the language and the modifications are the accent marks. Epigenetic marks change the way genes are expressed. The promise of epigenetics is that it tells us about the cell, it's a way to define the cell that's different than just looking at gene expression levels. We could look at any kind of cell and it will have specialized epigenetic patterns. There are two types of modifications: DNA methylation and histone modification. DNA methylation goes awry in cancers so if we knew the normal pattern of methylation and then looked at the pattern of methylation in a tumor we could see what changes were taking place and we could see which genes were being affected.

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Epigenetics - Genome.gov

During the discussion of disparities in cancer care, one panelist explained that the National Institutes of Health definition of precision medicine is broader than most people realize.

A flashpoint in the discussion of disparities in cancer care concerns data:If most of the data collected on genetic mutations come from White Europeans, what insights might we have missed? Will approved therapies offer the same level of efficacy in patients of color?

More importantly, what data beyond a persons genetics are not accounted for in todays clinical trials that could affect cancer outcomes? And how can artificial intelligence (AI) enable these factors to be part of the care equation?

During the discussion on cancer care disparities at Patient-Centered Oncology Care, Karen Winkfield, MD, PhD, executive director of the Meharry-Vanderbilt Alliance, asked John Carpten, PhD, of the Keck Schoolof Medicine at the University of Southern California Norris Comprehensive Cancer Center the following question: If we are talking about getting the right treatment to the right patient at the right time, what are some of thedata points that were currently missing?

The answer, Carpten replied, starts with the basic concept of precision medicine itself. And this is broader than most people realize if one looks at the definition given by the National Institutes of Health (NIH), he said.

"Im going to say this sensitivelyits consistently dumbed down to performing a genetic assay and trying to understand how to manage disease based on the individuals genetics," Carpten pointed out. "But if youlook at the NIH definition, it broadens it: it talks about lifestyle [and] environmental factors that can also [have] a significant impact on individual exposures."

These can include stresses, the built environment, and other factors that affect a persons living condition, Carpten said, in addition to their genetic ancestry. This area, epigenetics, involves individual behaviors and external factors that can alter how genes work. Epigenetics plays a huge role in cancer because if these other factors are not taken into account, targeting a patients mutation wont bring about the expected result.

"There are so many aspects of managing disease that go beyond just, 'Theres an alteration, its linked to this drug, so that drug should be effective in that setting. And we know that thats not always the case because there are so many other things that can impact that individuals response,' " Carpten said.

The future, he continued, should involve building cancer care models that would take both genetic and epigenetic factors into account. Winkfield used the example of smoking and how a mothers smoking during pregnancy can affect multiple generations of a family.

The more data we generate, the more we learn, and the more we can contribute to the model," Carpten said. "My hope is that it wont be about one measurement, it will be about a model. And in order to develop those models, we have to perform the studies that generate the data."

An opportunity exists for trauma, poverty, and institutional racism, for example, to finally be factored into such a model. "Im starting to be more vocal about the fact that racism is trauma, right? Its generational trauma," said Winkfield.

According to Carpten, models are beginning to take structural racism into account, including how exposure to environmental and social stressors affected the rate of reactive oxygen species development. This, in turn, led to effects such as chronic inflammation that are known to increase cancer risk. For all his excitement over the possibilities of AI, Carpten offered a warning: disparities could be exacerbated if not everyone has access. We have to take it one step at a time," he said. "[but] I think weve made a lotof progress."

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Genetics, Epigenetics, and Cancer: What Data Are We Missing? - AJMC.com Managed Markets Network

This article was originally published here

J Cardiovasc Pharmacol. 2021 Dec 10. doi: 10.1097/FJC.0000000000001201. Online ahead of print.

ABSTRACT

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has significant implications for patients with concomitant cardiovascular disease (CVD), as they are the population at the greatest risk of death. The treatment of such patients and complications may represent a new challenge for the fields of cardiology and pharmacology. Thus, understanding the involvement of this viral infection in CVD might help to reduce the SARS-CoV-2 multiorgan potential of aggressiveness. SARS-CoV-2 disturbs the host epigenome and several epigenetic processes involved in the pathophysiology of COVID-19 that can directly affect the function and structure of the cardiovascular system (CVS). Hence, it would be relevant to identify epigenetic alterations that directly impact CVS physiology after SARS-CoV-2 infection. This could contribute to the view of this virus-induced CVS injury and direct forthcoming tackles for COVID-19 treatment to reduce mortality in patients with CVD. Targeting epigenetic marks could offer strong evidence for the development of novel antiviral therapies, especially in the context of COVID-19-related CVS damage. In this review, we address some of the main signaling pathways which are currently known as being involved in COVID-19 pathophysiology and the importance of this glint on epigenetics and some of its modifiers (epidrugs) to control the unregulated epitope activity in the context of SARS-CoV-2 infection, COVID-19, and underlying CVD.

PMID:34935698 | DOI:10.1097/FJC.0000000000001201

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Can epigenetics help solve the puzzle between concomitant cardiovascular injury and severity of COVID-19? - DocWire News

The genomics market was valued at US$ 19,084.74 million in 2019 and is projected to reach US$ 49,996.15 million by 2027; it is expected to grow at a CAGR of 13.1% from 2020 to 2027.

According The Insight Partners study on Genomics Market Forecast to 2027 COVID-19 Impact and Global Analysis by Technology, Product & Service, Application, End User, The report highlights trends existing in the market, and drivers and hindrances pertaining to the market growth.

The report emphasizes on parameters such as market trends, technological advancements, market dynamics, and leading companys competitive landscape analysis to offers insights and in-depth analysis of the Genomics Market.

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Market Insights

Growing Funding for Genomics Drives Genomics Market Growth

Genomic sequencing is rapidly transitioning into clinical practice. Also, substantial government investments, totaling over US$ 4 billion in at least 14 countries, are supporting its implementation into healthcare systems. These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to the implementation and gathering evidence for broader adoption, which is bolstering the market growth. The UK announced the worlds largest genome project as a part of 200 million publicprivate collaboration between charities and pharma. The UK has already developed the largest genome database in the world through the 100,000 Genomes Project. Led by Innovate UK as part of UK Research and Innovation, the project will fund researchers and industries to combine data and real-world evidence from UK health services and create new products and services that diagnose diseases quickly and more efficiently. In November 2018, Stilla Technologies announced that it had completed a US$ 18.3 million (16 million) Series A financing round led by Illumina Ventures. The company will use funds to commercialize its Naica digital PCR system and develop clinical applications. Further, on June 2020, Base Genomics, an Oxford, England, UK-based epigenetics company, closed a seed funding round of US$11 million (9 million GBP).

COVID-19 first began in Wuhan (China) during December 2019 and since then it has spread at a fast pace across the globe. The US, India, Brazil, Russia, France, the UK, Turkey, Italy, and Spain are some of the worst affected countries in terms confirmed cases and reported deaths. The COVID-19 has been affecting economies and industries in various countries due to lockdowns, travel bans, and business shutdowns.

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Based on technology, the genomics market is segmented into sequencing, microarray, PCR, nucleic acid extraction and purification, and others. The sequencing segment held the largest share of the market in 2019, whereas the microarray segment is anticipated to register the highest CAGR during the forecast period. The market growth for the microarray segment is attributed to increasing use of technology in the diagnosis of infectious and genetic diseases, drug discovery, pharmacogenomic research, cancer diagnostics, and forensic applications. Additionally, the microarray technology is also used in immunology research such as the study of the relation between phenotype and gene expression, activation and differentiation of immune cells, regulation of immune responses, analysis of the molecular mechanisms of allergy, and immunological pharmacology.

Based on product & services, the genomics market is segmented into instruments/systems, consumables, and services. The consumables segment held the largest share of the market in 2019, whereas the services segment is anticipated to register the highest CAGR during the forecast period. The market growth of the consumables segment is attributed to rising government funding and surging number of genomics projects, decreasing sequencing costs, growing application areas of genomics, and the entry of new players and start-ups in the genomics field.

Based on application, the genomics market is segmented into diagnostics, drug discovery & development, precision/personalized medicine, agriculture & animal research, and others. The diagnostics segment held the largest share of the market in 2019, and the same segment is estimated to register the highest CAGR during the forecast period. The clinical applications of genomic technologies are vast and offer opportunities to enhance diagnosis and treatment capabilities for chronic disease. For instance, they offer huge potential in gene discovery and diagnosis of rare monogenic disorders.

Based on end user, the genomics market is segmented into research centers, hospitals & clinics, pharmaceutical & biotechnology companies, and other end users. The research centers segment held the largest share of the market in 2019, whereas the hospitals & clinics segment is estimated to register the highest CAGR during 20202027.

Genomics Market : Competitive Landscape and Key Developments

Illumina, Inc.,Danaher,F. HOFFMANN-LA ROCHE LTD.,BIO-RAD LABORATORIES INC.,General Electric Company,Thermo Fisher Scientific Inc.,Agilent Technologies, Inc.,Eurofins Scientific,QIAGEN,BGI

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Genomics Market Revenue to Cross US$ 49996.15 by 2027: The Insight Partners - Digital Journal