Genomics plus human intelligence

The power of gene sequencing to solve puzzles when combined with human Read more

'Master key' microRNA has links to both ASD and schizophrenia

Recent studies of complex brain disorders such as schizophrenia and autism spectrum disorder (ASD) have identified a few "master keys," risk genes that sit at the center of a network of genes important for brain function. Researchers at Emory and the Chinese Academy of Sciences have created mice partially lacking one of those master keys, called MIR-137, and have used them to identify an angle on potential treatments for ASD. The results were published this Read more

Shape-shifting RNA regulates viral sensor

OAS senses double-stranded RNA: the form that viral genetic material often takes. Its regulator is also Read more

cardiology

How white blood cells limit muscle regeneration

A paper from cardiologist Aloke Finn and colleagues (published Wednesday, Aug. 5 in Nature Communications) describes how the protein CD163, produced by macrophages, puts the brakes on muscle repair after ischemic injury in mice. Here’s why we think this paper is interesting.

*Speculatively, there are connections to the recent wave of “young blood cures old body” parabiosis research. Increased CD163 is a marker of aging in humans. Maybe low levels of CD163 are part of how young blood is restorative.

*Translational potential — it wouldn’t be too hard to make an antibody against human CD163. Something that blocks CD163 could possibly be used to treat muscle breakdown, which occurs in response to injury, inactivity and in diseases such as cancer and diabetes.

*Finn says his team was surprised to find that mice lacking CD163, tested in experiments where blood flow is restricted in one leg, showed increased blood vessel and muscle growth in the other leg. It looks like part of CD163’s role is to limit muscle regeneration to the site of injury. Read more

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Really? I had a heart attack?

A recent Harvard study, published in Circulation, found a surprising level of inconsistency between what medical records say about whether people had a heart attack and what they report themselves in surveys.

About a quarter of Medicare patients who said in a survey that they previously had a heart attack have no record of having any heart-related hospital admission. Conversely, about one-third of patients who, according to Medicare, experienced a heart attack said they hadn’t.

This finding is consistent with an Emory study from cardiologists Neal Dickert and Habib Samady, in which participants in a clinical trial were interviewed just a couple days after the initial procedure. The trial was testing a “post-conditioning” modification of angioplasty+stenting performed during treatment for a heart attack. Just over half (55 percent) of the participants initially remembered being asked to participate when asked. Read more

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Leslee Shaw explains coronary artery calcium scoring

On Thursday, cardiology researcher Leslee Shaw, PhD joined an exclusive club at Emory with her 2015 Dean’s Distinguished Faculty Lecture and Award.* Shaw is the co-director of Emory’s Clinical Cardiovascular Research Institute and research director of Emory Women’s Heart Center. Her lecture focused on the utility of coronary artery calcium (CAC) scoring in predicting cardiovascular disease.

Much cardiovascular risk research has focused on finding imaging or biomarker tests that can provide doctors with cost-effective decision-making power. One prominent question: should the patient take cholesterol-reducing statins? These tests should provide information above and beyond the Framingham Risk Score or its ACC/AHA update, which incorporates information about a patient’s age, sex, cholesterol/HDL, blood pressure and diabetes status.

CAC scoring is a good place to start, Shaw said, since it is a standardized, relatively inexpensive test that measures the buildup of calcium in atherosclerotic plaque, and the radiation dose is low compared with other cardiac imaging techniques. Read more

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Lab Land looking back: Top ten themes for 2014

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 diverting some of these topics into the 2015 crystal ball, I corralled them into themes.
1. Cardiac cell therapy
PreSERVE AMI clinical trial led by cardiologist Arshed Quyyumi. Emory investigators developing a variety of 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 using parathyroid hormone bone drug to mobilize cells for stroke treatment.
3. Epigenetics
Many colors in the epigenetic palette (hydroxymethylation). Valproate – epigenetic solvent (anti-seizure –> anti-cancer). Methylation in atherosclerosis model (Hanjoong Jo). How to write conservatively about epigenetics and epigenomics.
4. Parkinson’s disease therapeutic strategies
Container Store (Gary Miller, better packaging for dopamine could avoid stress to neurons).
Anti-inflammatory (Malu Tansey, anti-TNF decoy can pass blood-brain barrier).
5. Personal genomics/exome sequencing
Rare disease diagnosis featured in the New Yorker. Threepart series on patient with GRIN2A mutation.
6. Neurosurgeons, like Emory’s Robert Gross and Costas Hadjpanayis, do amazing things
7. Fun vs no fun
Fun = writing about Omar from The Wire in the context of drug discovery.
No fun (but deeply moving) = talking with patients 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
Image guided cancer surgery (Shuming Nie/David Kooby). Cancer immunotherapy chimera (Jacques Galipeau). Fine tuning old school chemo drug cisplatin (Paul Doetsch)
10. Tie between fructose effects on adolescent brain (Constance Harrell/Gretchen Neigh) and flu immunology (embrace the unfamiliar! Ali Ellebedy/Rafi Ahmed)
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In landmark study of cell therapy for heart attack, more cells make a difference

Patients who receive more cells get significant benefits. That’s a key lesson emerging from a clinical trial that was reported this week at the American Heart Association meeting in Chicago.

In this study, doctors treated heart attack patients with their own bone marrow cells, selected for their healing potential and then reinjected into the heart, in an effort to improve the heart’s recovery. In the PreSERVE-AMI phase II trial, physicians from 60 sites (author list) treated 161 patients, making the study one of the largest to assess cell therapy for heart attacks in the United States. The study was sponsored by NeoStem, Inc.

“This was an enormous undertaking, one that broke new ground in terms of assessing cell therapy rigorously,” says the study’s principal investigator, Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine and co-director of the Emory Clinical Cardiovascular Research Institute. “We made some real progress in determining the cell type and doses that can benefit patients, in a group for whom the risks of progression to heart failure are high.” Read more

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Plaque erosion: heart attacks triggered by a whimper, not a bang

Cardiologist Bob Taylor and colleagues have a new paper in PLOS One this week, looking at the biomechanical forces behind plaque erosion.

Plaque erosion is a mechanism for blood clots formation in coronary arteries that is not as well-understood as its more explosive counterpart, plaque rupture. Plaque erosion disproportionally affects women more than men and is thought to account for most heart attacks in younger women (women younger than 50).

“We believe that this work has implications for our better understanding of the underlying biology of coronary artery disease in women,” Taylor says. The first author of the paper is biomedical engineering graduate student Ian Campbell, who now has his PhD. The team collaborated with cardiovascular pathologist Renu Virmani in Maryland.

Cardiologists have well-developed ideas for how plaque rupture works*; see the concept of vulnerable plaque. Cholesterol and inflammatory cells build up in the coronary arteries over several years. At one point in a particular artery, the plaque has a core of dying inflammatory cells, covered by a fibrous cap. If the cap is thin (the patterns of blood flows near the cap influence this), there is a risk that the cap will break and the contents of the core will spill out, triggering a blood clot nearby.

Plaque erosion is more mysterious and can occur more gradually, the researchers have found. Read more

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What are exosomes?

Biomedical engineer Mike Davis reports he has obtained NHLBI funding to look into therapeutic applications of exosomes in cardiology. But wait. What are exosomes? Time for an explainer!

Exosomes are tiny membrane-wrapped bags, which form inside cells and are then spat out. They’re about 100 or 150 nanometers in diameter. That’s smaller than the smallest bacteria, and about as large as a single influenza or HIV virion. They’re not visible under a light microscope, but are detectable with an electron microscope.

Scientific interest in exosomes shot up after it was discovered that they can contain RNA, specifically microRNAs, which inhibit the activity of other genes. This could be another way in which cells talk to each other long-distance, besides secreting proteins or hormones. Exosomes are thus something like viruses, without the infectivity.

Since researchers are finding that microRNAs have potential as therapeutic agents, why not harness the vehicles that cells use to send microRNAs to each other? Similarly, if so much evidence points toward the main effect of cell therapy coming from what the cells make rather than the cells themselves, why not simply harvest what the cells make? Read more

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Epigenetic changes in atherosclerosis

If someone living in America and eating a typical diet and leading a sedentary lifestyle 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 healthier and exercise more.”

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Let’s leave aside 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 vessels when someone has healthy or unhealthy blood flow patterns?

Biomedical engineer Hanjoong Jo and his colleagues published a 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. Specifically, the durable DNA modification known as methylation is involved, and blocking DNA methylation with a drug used for treating some forms of cancer can prevent atherosclerosis in their model. This suggests that blood vessels retain an epigenetic imprint reflecting the blood flow patterns they see.

Although treating atherosclerosis with the drug decitabine is not a viable option clinically, Jo’s team was able to find several genes that are silenced by disturbed blood flow and that need DNA methylation to stay shut off. A handful of those genes have a common mechanism of regulation and may be good therapeutic targets for drug discovery.

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Thyroid makes young mouse hearts grow

The entire heart muscle in young children may hold untapped potential for regeneration, new research suggests.

For decades, scientists believed that after a child’s first few days of life, cardiac muscle cells did not divide. Instead, the assumption was that the heart could only grow by having the muscle cells become larger.

Cracks were already appearing in that theory. But new findings in mice, published May 8 in Cell, provide a dramatic counterexample — with implications for the treatment of congenital heart disorders in humans. Read more

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Packaging stem cells in capsules for heart therapy

Stem cell therapy for heart disease is happening. Around the world, thousands of heart disease patients have been treated in clinical studies with some form of bone marrow cells or stem cells. But in many of those studies, the actual impact on heart function was modest or inconsistent. One reason is that most of the cells either don’t stay in the heart or die soon after being introduced into the body.

Cardiology researchers at Emory have a solution for this problem. The researchers package stem cells in a capsule made of alginate, a gel-like substance. Once packaged, the cells stay put, releasing their healing factors over time.

Researchers used encapsulated mesenchymal stem cells to form a “patch” that was applied to the hearts of rats after a heart attack. Compared with animals treated with naked cells (or with nothing), rats treated with the capsule patches displayed increased heart function, reduced scar size and more growth of new blood vessels a month later. In addition, many more of the encapsulated cells stayed alive. Read more

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