Gene editing reverses Huntington's in mouse model

This is a concrete example, not yet clinical, of what can be done with CRISPR/Cas9 gene Read more

Urine tests for prostate cancer could reduce biopsies

Urine RNA tests could reduce the number of biopsies by giving a preview of a cancer's aggressiveness. Featuring Martin Sanda and Carlos Read more

Mitochondrial blindness -- Newman's Emory story

Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy. The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials Read more

Heart

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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Spider fibers in smooth muscle cells

This image submitted by Thalita Abrahao won second place at the Postdoctoral Research Symposium Thursday. Abrahao, a postdoc in Kathy Griendling’s lab, is studying vesicle trafficking in vascular smooth muscle cells.

Thalita Abrahao -- Kathy Griendling lab

Thalita Abrahao — Kathy Griendling lab

Griendling’s lab has been looking into how the enzyme Nox4 and its partner Poldip2 are involved in cell migration, and Abrahao was investigating if vascular smooth muscle cells that have less Poldip2 have changes in protein processing.

Here, green represents beta-tubulin, a protein making up fine-looking fibers (microtubules) extending through the cell. Purple represents Sec23, part of the process of vesicle trafficking and protein secretion. White indicates when beta-tubulin and Sec23 are both present. Orange marks DNA in the nucleus.

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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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Education is a life preserver, after heart attack

For the last decade, cardiology researchers have been collecting detailed information on the patients who come through Emory’s catheterization labs. The density of data (close to 7000 people) can make it possible to achieve some insights about mortality in American society.

Cardiology research fellow Salim Hayek, MD, presented some provocative findings yesterday in a poster competition at the American College of Physicians meeting in Boston. He has been working with Arshed Quyyumi, MD and colleagues at Emory’s Clinical Cardiovascular Research Institute.

Their analysis shows “college education as a discrete indicator of socioeconomic status was an independent predictor of survival.”

A key thing to remember when looking at this data is that most of the people in the cath lab at a given moment are not actually having a heart attack — just 13 percent are. (Abstract/poster available upon request). However, there’s enough suspicion or history of heart disease for doctors to take a look inside; most of them have hypertension and coronary artery disease, and many have had a heart attack in the past. The group is mostly men, average age 63. Read more

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Honokiol, Jack of all trades

Emory dermatologist Jack Arbiser discovered the anti-angiogenic properties of honokiol, a compound derived from magnolia cones, more than a decade ago. Since then, honokiol has been found to have anti-inflammatory, anti-oxidant and anticancer properties.

A paper published Tuesday in Nature Communications from researchers at the University of Chicago shows that honokiol inhibits the mitochondrial enzyme Sirt3, which has connections to longevity. Manesh Gupta and colleagues demonstrate that honokiol can block cardiac hypertrophy in mice, a finding with possible relevance for the treatment of heart failure.

Sirt3 has been linked both genetically to human life span, and until now, the only way to increase levels of Sirt3 was old-fashioned calorie restriction and/or endurance exercise.

The authors write: It is believed that Sirt3 does not play a role in embryonic development, but rather it fine tunes the activity of mitochondrial substrates by lysine deacetylation to protect cells from stress… To the best of our knowledge, this is the first report describing a pharmacological activator of Sirt3.

 

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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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ACC 2015: Newer heart risk calculator may better accounts for racial differences

A risk calculator for cardiovascular disease, developed as a companion for the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, may account for racial differences in sub-clinical vascular function better than the Framingham Risk Score, Emory cardiology researchers say.

Their findings are scheduled for presentation Monday at the American College of Cardiology meeting in San Diego.

African Americans, especially men, tend to have a higher prevalence of cardiovascular disease, but this differences are not reflected in the Framingham Risk score. Arterial stiffness is a sign of heart disease risk that tends to appear more prominently among African Americans than whites. Cardiovascular research fellow Jia Shen, MD, MPH, and Emory colleagues analyzed data on arterial stiffness and structure from 1235 people – 777 whites and 458 African-Americans — enrolled in two large studies (Center for Health Discovery and Well Being and META-Health). Read more

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Who regulates the regulators? Drosha

MicroRNAs have emerged as important master regulators in cells, since each one can shut down several target genes. Riding on top of the master regulators is Drosha, the RNA-cutting enzyme that initiates microRNA processing in the nucleus. Drosha and its relative Dicer have been attracting attention in cancer biology, because they are thought to be behind a phenomenon where cancerous cells can “infect” their healthy neighbors via tiny membrane-clothed packets called exosomes.

At Emory, pharmacologist Zixu Mao and colleagues recently published in Molecular Cell their findings that Drosha is regulated by stress (experimentally: heat or peroxide) through p38 MAP kinase.

Although we mention relevance to cancer above, this is one of those basic cell biology findings that may have applicability to several areas of medicine. Alterations in miRNA processing have been linked to neurodegenerative disease (Fragile X-associated tremor/ataxia syndrome, for one example). MicroRNA-packed exosomes are also being studied by biomedical engineers as potential therapeutic tools in regenerative medicine, so knowing what cellular stress does to miRNA production could be useful. Read more

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Extend that New Year’s energy – to what benefit?

Surveys indicate that many of us make New Year’s resolutions to eat more healthily or exercise more frequently, yet do not sustain the enthusiasm of January throughout the year.

What if the burst of energy and good intentions could be maintained over a longer period, perhaps with the help of a coach? What kinds of health benefits would appear?

Researchers from Emory and Georgia Tech recently published an analysis of the changes in the health profiles in 382 Center for Health Discovery & Well Being participants who completed a one-year evaluation.

The senior author is Greg Gibson, PhD, professor of biology and director of the Center for Integrative Genomics at Georgia Tech. Georgia Tech postdoctoral fellow Rubina Tabassum, now at the University of Helsinki, is the first author.

“What do most people in developed countries need to do? Eat better, exercise more regularly and stress less,” Gibson says. “It’s unclear whether most of the impact comes from the interaction with partners, or simply from participation and goal-setting, but the overall effect is quite good.”

The main points:

*These are “essentially healthy” people — healthier than the general population in the United States – but almost half started out with high blood pressure and cholesterol levels. There was no control group, and not everyone pursued the same exact program. The average age was 48 years and 28 percent of the group was considered obese. That’s less than the United States population as a whole.

*On average, the 382 participants lost a moderate amount of weight (it works out to about three pounds) and saw their blood pressure and LDL-cholesterol go down significantly over that first year (121 to 116 mmHG for systolic BP, 112 to 105 mg/dL for LDL-C). They also reported lower scores for depression and anxiety.

Read more

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Stem cell/cardiology researcher Hee Cheol Cho joins Emory

Please welcome stem cell/cardiology researcher Hee Cheol Cho to Emory. Starting in September, Cho joined the Wallace H Counter Department of Biomedical Engineering at Georgia Tech and Emory, and Emory-Children’s Pediatric Research Center. He and his team will focus on developing gene-and cell-based therapies for cardiac arrhythmias. Their research will adding to and complement the research of several groups, such as those led by Chunhui Xu, Young-sup Yoon, Mike Davis and W. Robert Taylor.

Cho comes from Cedars-Sinai Medical Center in Los Angeles, where he specialized in understanding cardiac pacemaker cells, a small group of muscle cells in the sinoatrial node of the heart that initiate cardiac contraction. These cells have specialized electrophysiological properties, and much has been learned in the last few years about the genes that control their development.

Cho and colleagues from Cedars-Sinai recently published a paper in Stem Cell Reports describing how the gene SHOX2 can nudge embryonic stem cells into becoming cardiac pacemaker cells. Read more

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