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It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After divertingÂ some of these topics into the 2015 crystal ball,Â I corralledÂ them into themes.
1. Cardiac cell therapy
PreSERVE AMI clinical trial led by cardiologist Arshed Quyyumi. Emory investigators developingÂ a variety ofÂ approaches to cardiac cell therapy.
2. Mobilizing the body’s own regenerative potential
Ahsan Husain’s work on how young hearts grow. Shan Ping Yu’s lab usingÂ parathyroid hormone boneÂ drug to mobilize cells for stroke treatment.
4. Parkinson’s disease therapeutic strategies
Container Store (Gary Miller, better packaging for dopamine could avoidÂ stress to neurons).
Anti-inflammatory (Malu Tansey, anti-TNF decoy can passÂ blood-brain barrier).
5. Personal genomics/exome sequencing
6. Neurosurgeons, likeÂ Emory’s Robert Gross and Costas Hadjpanayis, do amazing things
7. Fun vsÂ no fun
Fun = writing about Omar from The Wire in the context of drug discovery.
No fun (but deeply moving) = talking with patientsÂ fighting glioblastoma.
8. The hypersomnia field is waking up
Our Web expert tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
10. Tie between fructose effects on adolescent brain (Constance Harrell/Gretchen Neigh) and flu immunology (embrace the unfamiliar! Ali Ellebedy/Rafi Ahmed)
Posted on January 7, 2015 by
Methylation, an epigenetic modification to DNA, can be thought of as a highlighting pen applied to DNAâ€™s text, adding information but not changing the actual letters of the text.
Are you still with me on the metaphors? If so, consider this wrinkle. (If not, more explanation here.)
Emory geneticist Peng Jin and his colleagues have been a key part of the discovery in the last few years that methylation comes in several colors. His lab has been mapping where 5-hydroxymethylcytosine or 5hmC appears in the genome and inferring how it functions. 5-hmC is particularly abundant in the brain.
Methylation, in the form of 5-methylcytosine or 5mC, is both a control button for turning genes off and a sign of their off state. 5hmC looks like 5mC, except it has an extra oxygen. That could be a tag for a removal, or a signal that aÂ gene is poised to be turned on.
Two recent papers on this topic:
Please recall that an enriched environment (exercise and mental stimulation) is good for learning and memory, for young and old. In the journalÂ Genomics, Jin and his team show that exposing mice to an enriched environmentÂ — a running wheel and a variety of toys — leads to a 60 percent reduction in 5hmC in the hippocampus, a region of the brain critical for learning and memory. Â The changes in 5hmC were concentratedÂ in genes having to do with axon guidance. Hat tip to the all-things-epigenetic site Epigenie.
In Genes and Development, structural biologist Xiaodong Cheng and colleagues demonstrateÂ that two regulatory proteins that bind DNA (Egr1 and WT1) respond primarily to oxidation of their target sequences rather than methylation. These proteins like plain old C and 5mC equally, but they donâ€™t like 5hmC or other oxidized forms of 5mC. â€œGene activity could plausibly be controlled on a much finer scale by these modifications than simply â€˜on or â€˜offâ€™,â€ the authors write.
Posted on October 8, 2014 by
In June a discussion came up on Twitter about scientific terms that are overused. I began to wonder whether I was contributing to the problem and may need to tighten up my use of the word â€œepigenetics.â€ Read more
Posted on July 22, 2014 by
If someone living in America and eating a typical diet and leading a sedentary lifestyleÂ lets a few years go by, we can expect plaques of cholesterol and inflammatory cells to build up in his or her arteries. We’re not talking “Super-size Me” here, we’re just talking average American. But then let’s say that same person decides: “OK, I’m going to shape up. I’m going to eat healthierÂ and exercise more.”
Let’s leave asideÂ whether low-carb or low-fat is best, and let’s say that person succeeds in sticking to his or her declared goals. How “locked in” are the changes in the blood vesselsÂ when someone has healthy or unhealthy blood flow patterns?
Biomedical engineer Hanjoong Jo and his colleagues published aÂ paper in Journal of Clinical Investigation that touches on this issue. They have an animal model where disturbed blood flow triggers the accumulation of atherosclerosis. They show that the gene expression changes in endothelial cells, which line blood vessels, have an epigenetic component.Â Specifically, the durable DNA modification known asÂ methylation is involved, and blocking DNA methylation with a drug used for treating some forms of cancer can prevent atherosclerosis in their model.Â This suggests that blood vessels retain an epigenetic imprint reflecting the blood flow patterns they see.
Although treating atherosclerosis with theÂ drug decitabine is notÂ a viable option clinically, Jo’s team was able to find severalÂ genes that are silenced by disturbed blood flow and that need DNA methylation to stay shut off. A handful of thoseÂ genes have aÂ common mechanism of regulationÂ and may be good therapeutic targets for drug discovery.
Posted on June 24, 2014 by
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 censorâ€™s pen. It doesnâ€™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.Â They’re used in medication or diet studies to demonstrate efficacy or suggest side effects.Â Â Theyâ€™re also used in longitudinal studies to see if particular exposures or characteristics (i.e. low birthweight) have long-term consequences.” Read more
Posted on April 9, 2014 by
Oncologist Johann Brandes and colleagues from Winship Cancer Institute have a recent study on the preventive effects of valproate, now prescribed for epilepsy and bipolar disorder, against head and neck cancer.
Published in Cancer, it was a clever example of number crunching, using data from the Veteransâ€™ Administration. If you want to know about the anticancer effects of a widely used drug, check whoâ€™s already taking it for another reason (25,000 veterans were taking it). The results suggest that valproate â€“ OR a drug that works with a similar mechanism â€“ might be used to prevent head and neck cancer in patients who are at high risk. Also see this related paper from Brandes and colleagues on chemoprevention in lung cancer.
However, any examination of valproate should take into account neurologist Kim Meadorâ€™s work on antiepileptic drugs taken by pregnant women — he was at Emory for several years but recently moved to Stanford. His work with the NEAD study definitively showed that valproate, taken during pregnancy, increases the risk of birth defects and intellectual disability in children.
Thereâ€™s even more about valproate: it might help tone-deaf adults learn to differentiate musical tones, according to one study. It has been used to enhance the reprogramming of somatic cells into induced pluripotent stem cells. It seems that valproate just shakes things up, turning on genes that have been off, erasing decisions that cells have already made.
Valproate is a tricky drug, with several modes of action: it blocks sodium channels, enhances the effects of the inhibitory neurotransmitter GABA, and inhibits histone deacetylases. Although the first two may be contributing to the antiepileptic effects, the last one may be contributing to longer-lasting changes. Histone deacetylases are a way a cell keeps genes turned off; inhibit them and you loosen things up, allowing the remodeling of chromatin and unearthing genes that were silenced.
In tumors, genes that prevent runaway growth are silenced. It may be that valproate is loosening chromatin enough to allow the growth control machinery to reemerge, although the effects observed in the Brandes paper are specific for head and neck cancer, and not other forms of cancer. The data suggest that valproate has a preventive effect with respect to smoking-related cancers and not viral-related cancers.
With adults at high risk of cancer recurrence, side effects from valproate may be more acceptable than in other situations. Even so, with follow-up research, it may be possible to isolate where the anticancer effects of valproate come from â€“ that is, which histone deacetylase in particular is responsible â€“ find a more specific drug, and avoid potential broad side effects.
Posted on April 1, 2014 by
Two feature articles in Nature this week on work by Emory scientists.
One is from Virginia Hughes (Phenomena/SFARI/MATTER), delving into Kerry Ressler’s and Brian Dias’ surprising discovery in mice that sensitivity to a smell can be inherited, apparently epigenetically. Coincidentally, Ressler will be giving next week’s Dean’s Distinguished Faculty lecture (March 12, 5:30 pm at the School of Medicine).
Posted on March 6, 2014 by
Peng Jin and collaborators led by Da-Hua Chen from the Institute of Zoology, Chinese Academy of Sciences have a new paper in Stem Cell Reports. They describe a souped-up method for producing iPS cells (induced pluripotent stem cells).
Production of iPS cells in the laboratory is becoming more widespread. Many investigators, including those at Emory, are using the technology to establish â€œdisease in a dishâ€ models and derive iPS cells from patient donations, turning them into tools for personalized medicine research.
Posted on February 27, 2014 by
This intriguing research has received plenty of attention, Â both when it was presented at the Society of Neuroscience meeting in the fall and then when the results were published in Nature Neuroscience.
The short summary is: researchers at Yerkes National Primate Research Center found that when a mouse learns to become afraid of a certain odor, his or her pups will be more Gafas Ray Ban Baratas sensitive to that odor, even though the pups have never encountered it.Â Both the parent mouse and pups have more space in the smell-processing part of their brains, called the olfactory bulb, devoted to the odor to which they are sensitive.
[Note: a feature on a similar phenomenon, transgenerational inheritance of the effects of chemical exposure, appeared in Science this week]
Somehow information about the parent’s experiences is being inherited. But how? Brian Dias and Kerry Ressler are now pursuing followup experiments to firmly establish what’s going on. They discuss their research in this video:
Posted on January 24, 2014 by
The 2012 Nobel Prize in Medicine was awarded to Shinya Yamanaka and John Gurdon for the discovery that differentiated cells in the body can be reprogrammed. This finding led to the development of â€œinduced pluripotent stem cells.â€
These cells were once skin or blood cells. Through a process of artificial reprogramming in the lab, scientists wipe these cellsâ€™ slates clean and return them to a state very similar to that of embryonic stem cells.Â But not exactly the same.
It has become clear that iPS cells can retain some memories of their previous state. This can make it easier to change an iPS cell that used to be a blood cell (for example) back into a blood cell, compared to turning it into another type of cell. The finding raised questions about iPS cellsâ€™ stability and whether http://www.troakley.com/ iPS cell generation â€“ still a relatively new technique â€“ would need some revamping for eventual clinical use.
It turns out that iPS cells and embryonic stem cells have differing patterns of methylation, a modification of DNA that can alter how genes behave even if the underlying DNA sequence remains the same. Some of these differences are the same in all iPS cells and some are unique for each batch of reprogrammed cells.
Posted on May 22, 2013 by