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

W. Robert Taylor

Regenerative Engineering & Medicine highlights

Last week on Friday, Lab Land attended the annual Regenerative Engineering & Medicine center get-together to hear about progress in this exciting area.

During his talk, Tony Kim of Georgia Tech mentioned a topic that Rose Eveleth recently explored in The Atlantic: why aren’t doctors using amazing “nanorobots” yet? Or as Kim put it, citing a recent review, “So many papers and so few drugs.”

[A summary: scaling up is difficult, testing pharmacokinetics, toxicity and efficacy is difficult, and so is satisfying the FDA.]

The talks Friday emerged from REM seed grants; many paired an Emory medical researcher with a Georgia Tech biomedical engineer. All of these projects take on challenges in delivering regenerative therapies: getting cells or engineered particles to the right place in the body.

For example, cardiologist W. Robert Taylor discussed the hurdles his team had encountered in scaling up his cells-in-capsules therapies for cardiovascular diseases to pigs, in collaboration with Luke Brewster. The pre-pig phase of this research is discussed in more detail here and here. 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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A spoonful of sugar helps infection detection

Congratulations to Kiyoko Takemiya, a postdoctoral fellow in Emory’s Division of Cardiology, working with W. Robert Taylor. At the recent American College of Cardiology meeting in Washington DC, she won first place in the competition for an ACC Foundation/ Herman K. Gold Young Investigators Award in Molecular and Cellular Cardiology.

The title of her research presentation was: A Novel Imaging Probe for the Detection of Subclinical Bacterial Infections Involving Cardiac Devices.

Takemiya, Taylor, and their colleagues (including Mark Goodman and Niren Murthy, formerly at Georgia Tech and now at UC Berkeley) developed a fluorescent probe that allows the detection of small levels of bacteria on cardiac devices. The probe was tested in rats, some of which had relatively mild local S. aureus infections. The fluorescent probe (PET is also under investigation) makes use of the properties of maltohexaose, a sugar that is taken up by bacteria but not mammalian cells.

Infection rates for implantable cardiac devices such as pacemakers have been rising, according to a 2012 paper in NEJM.

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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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AHA meeting highlights — an Emory-centric view

Poring over the abundance of information presented at major scientific meetings is like trying to drink from a firehose.  Imposing an Emory-centric filter on this year’s American Heart Association Scientific Sessions meeting in Los Angeles, here are three highlights, with a shoutout to the AHA journal Circulation, which provides a database of meeting abstracts.

Alginate encapsulation, a therapeutic delivery tactic to get stem cells to stay in the heart

Presenter Rebecca Levit, MD, a postdoc in cardiology division chair W. Robert Taylor’s laboratory, was a finalist for an Early Career Investigator Award.

 Stem cell therapies for myocardial repair have shown promise in preclinical trials, but lower than expected retention and viability of transplanted cells. In an effort to improve this, we employed an alginate encapsulation strategy for human mesenchymal stem cells (hMSCs) and attached them to the heart with a biocompatible PEG hydrogel patch in a rat MI model. Encapsulation allows for diffusion of pro-angiogenic cytokines and growth factors made by the hMSCs while maintaining them at the site of implantation…Alginate encapsulated hMSCs attached to the heart with a hydrogel patch resulted in a highly significant improvement in left ventricular function after acute myocardial infarction. The mechanism for this markedly enhanced effect appears to be increased cell survival and retention.

 Note: alginate already has a wide variety of uses, for example in culinary arts and to make dental impressions.

suPAR, a biomarker connected with depression, inflammation and cardiovascular outcomes. Step back, C-reactive protein

Depression, inflammation (Manocha, Vaccarino)

Cardiovascular outcomes (Eapen, Quyyumi)

Coronary microvascular dysfunction (Corban, Samady)

Predicting mental-stress myocardial ischemia via a public speaking test

A study probing myocardial ischemia (a lack of blood flow to the heart) induced by psychological stress, described in this Emory Public Health article. The presentation by Ronnie Ramadan examines physiological responses to a public speaking test as a way of predicting more severe problems.

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