Update on SIV remission studies

Recently presented insights on how an antibody used to treat intestinal diseases can suppress Read more

Granulins treasure not trash - potential FTD treatment strategy

Granulins are of interest to neuroscientists because mutations in the granulin gene cause frontotemporal dementia (FTD). However, the functions of granulins were previously Read more

Blood vessels and cardiac muscle cells off the shelf

How to steer induced pluripotent stem cells into becoming endothelial cells, which line blood Read more

Alicia Smith

How estrogen modulates fear learning — molecular insight into PTSD in women

Low estrogen levels may make women more susceptible to the development of post-traumatic stress disorder (PTSD) at some points in their menstrual cycles or lifetimes, while high estrogen levels may be protective.

New research from Emory University School of Medicine and Harvard Medical School provides insight into how estrogen changes gene activity in the brain to achieve its protective effects.

The findings, published in Molecular Psychiatry, could inform the design of preventive treatments aimed at reducing the risk of PTSD after someone is traumatized.

The scientists examined blood samples from 278 women from the Grady Trauma Project, a study of low-income Atlanta residents with high levels of exposure to violence and abuse. They analyzed maps of DNA methylation, a modification to the shape of DNA that is usually a sign of genes that are turned off.

The group included adult women of child-bearing age, in which estrogen rises and falls with the menstrual cycle, and women that had gone through menopause and had much lower estrogen levels.

“We knew that estrogen affects the activity of many genes throughout the genome,” says Alicia Smith, PhD, associate professor and vice chair of research in the Department of Gynecology and Obstetrics at Emory University School of Medicine. “But if you look at the estrogen-modulated sites that are also associated with PTSD, just one pops out.”

That site is located in a gene called HDAC4, known to be critical for learning and memory in mice. Genetic variation in HDAC4 among the women was linked to a lower level of HDAC4 gene activity and differences in their ability to respond to and recover from fear, and also differences in “resting state” brain imaging. Women with the same variation also showed stronger connections in activation between the amygdala and the cingulate cortex, two regions of the brain involved in fear learning. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Gestational age estimated via DNA methylation

Researchers have developed a method for estimating developmental maturity of newborns. It is based on tracking DNA methylation, a structural modification of DNA, whose patterns change as development progresses before birth.

The new method could help doctors assess developmental maturity in preterm newborns and make decisions about their care, or estimate the time since conception for a woman who does not receive prenatal care during pregnancy. As a research tool, the method could help scientists study connections between the prenatal environment and health in early childhood and adulthood.

How advanced is the development of a newborn, possibly preterm baby? Geneticists have developed a method for estimating gestational age by looking at DNA methylation.

The study, led by Alicia Smith, PhD and Karen Conneely, PhD, used blood samples from more than 1,200 newborns in 15 cohorts from around the world. The results are published in Genome Biology.

Smith is an associate professor and vice chair of research for the Department of Gynecology and Obstetrics in the School of Medicine, and Conneely is an assistant professor in the Department of Human Genetics. The first author, Anna Knight, is a graduate student in the Genetics and Molecular Biology Program.

Gestational age, is normally estimated by obstetricians using ultrasound during the first trimester, by asking a pregnant woman about her last menstrual period, or by examining the baby at birth. Ultrasound is considered to be the most precise estimate of gestational age. This work extends upon earlier studies of DNA methylation patterns that change over development and predict age and age-related health conditions in children and adults.

The Emory team gathered DNA methylation data from previous studies examining live births and health outcomes, and used an unbiased statistical learning approach to select 148 DNA methylation sites out of many thousands in the genome. By examining methylation at those sites, gestational age could be accurately estimated between 24 and 44 weeks, the authors report. The median difference between age determined by DNA methylation and age determined by an obstetrician estimate was approximately 1 week.

The researchers also found that the difference between a newborn’s age predicted by DNA methylation and by an obstetrician may be another indicator of developmental maturity, and is correlated with birthweight, commonly used as an indicator of perinatal health. Read more

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Trend: epigenomics

Nature News recently described a trend noticeable at Emory and elsewhere. That trend is epigenomics: studying the patterns of chemical groups that adorn DNA sequences and influence their activity. Often this means taking a comprehensive genome-wide look at the patterns of DNA methylation.

DNA methylation is a chemical modification analogous to punctuation or a highlighter or censor’s pen. It doesn’t change the letters of the DNA but it does change how that information is received.

One recent example of epigenomics from Emory is a collaboration between psychiatrist Andrew Miller and oncologist Mylin Torres, examining the long-lasting marks left by chemotherapy in the blood cells of breast cancer patients.

Their co-author Alicia Smith, who specializes in the intersection of psychiatry and genetics, reports “EWAS or epigenome-wise association studies are being used in complex disease research to suggest genes that may be involved in etiology or symptoms.  They’re used in medication or diet studies to demonstrate efficacy or suggest side effects.   They’re also used in longitudinal studies to see if particular exposures or characteristics (i.e. low birthweight) have long-term consequences.” Read more

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