Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Why malaria vaccine development is hard

In recognition of World Malaria Day, Lab Land will have a series of posts from Taryn McLaughlin, a graduate student in Emory’s IMP program. Her posts will set the stage for upcoming news about malaria research at Emory and Yerkes. Taryn is part of Cheryl Day’s lab and is also an associate producer with the AudiSci podcast.

Those of us in the US are fortunate to not have to consider malaria in our day-to-day lives. Globally though, malaria is a serious public health threat with nearly 3.2 billion people at risk and close to half a million deaths every year. The scientific community has been developing malaria vaccines for decades. Yet a robust vaccine still remains elusive. Why?

IMP graduate student Taryn McLaughlin

IMP graduate student Taryn McLaughlin

One set of barriers comes from economics: malaria’s strongest impact is in developing countries. But there is just as strong a case to be made for scientific obstacles. Frankly, the parasite (technically a bunch of species of microbes that I’ll just lump together under the umbrella term Plasmodium) that causes malaria is just smarter than we are.

I’m only kidding, but it is a fascinating organism. Its complexity makes it difficult to pin down and also interesting to write about. But before we talk about why Plasmodium is such a pain, let’s first discuss what exactly makes an effective vaccine. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Manipulating motivation in mice

Emory researchers have identified molecular mechanisms that regulate motivation and persistence in mice. Their findings could have implications for intervention in conditions characterized by behavioral inflexibility, such as drug abuse and depression.

Scientists showed that by manipulating a particular growth factor in one region of the brain, they could tune up or down a mouse’s tendency to persist in seeking a reward. In humans, this region of the brain is located just behind the eyes and is called the medial orbitofrontal cortex or mOFC.

“When we make decisions, we often need to gauge the value of a reward before we can see it — for example, will lunch at a certain restaurant be better than lunch at another, or worth the cost,” says Shannon Gourley, PhD, assistant professor of pediatrics and psychiatry at Emory University School of Medicine. “We think the mOFC is important for calculating value, particularly when we have to imagine the reward, as opposed to having it right in front of us.”

The results were published Wednesday in Journal of Neuroscience.

Shannon Gourley, PhD

Being able to appropriately determine the value of a perceived reward is critical in goal-directed decision making, a component of drug-seeking and addiction-related behaviors. While scientists already suspected that the medial orbitofrontal cortex was important for this type of learning and decision-making, the specific genes and growth factors were not as well-understood.

The researchers focused on brain-derived neurotrophic factor (BDNF), a protein that supports the survival and growth of neurons in the brain. BDNF is known to play key roles in long-term potentiation and neuronal remodeling, both important in learning and memory tasks. Variations in the human gene that encodes BDNF have been linked with several psychiatric disorders.

Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Please vote in Best Image contest

Emory University School of Medicine’s Office of Postdoctoral Education has posted ten dazzling images from current Emory biomedical research here, and you can vote on your favorites (VOTE HERE). The Best Image contest sets the stage for the Postdoctoral Research Symposium on May 19. A gallery showing all ten at once — larger than what you see below– is also available at this site.

Voting lasts only until Sunday (4/23), since the three contest-winning images will be part of the abstract book and other materials, and the organizers need to complete printing orders soon.Screen Shot 2016-04-19 at 12.46.17 PM

Lab Land is looking forward to learning more about the images. For now, it is fun to guess what they are. In the gallery, each one is labeled with the name of the researcher who submitted them. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Football metabolomics

Following on the recent announcement of the Atlanta Hawks training center, here’s a Nov. 2015 research paper from Emory’s sports cardiologist Jonathan Kim, published in Annals of Sports Medicine and Research.

Jonathan Kim, MD

Kim and colleagues from Emory Clinical Cardiovascular Research Institute studied blood samples from 15 freshman football players at Georgia Tech before and after their first competitive season. The researchers had the help of metabolomics expert Dean Jones. Kim has also previously studied blood pressure risk factors in college football players.

On average, football players’ resting heart rate went down significantly (72 to 61 beats per minute), but there were no significant changes in body mass index or blood pressure. The research team observed changes in players’ amino acid metabolism, which they attribute to muscle buildup.

This finding may seem obvious, but imagine what a larger, more detailed analysis could do: start to replace locker room myths and marketing aimed at bodybuilders with science. This was a small, preliminary study, and the authors note they were not able to assess diet or nutritional supplementation. Read more

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More on Alzheimer’s-blood pressure link

Emory’s Alzheimer’s Disease Research Center recently announced a grant that will support studies on the connections between blood pressure regulation and Alzheimer’s disease. It focuses on the roles of the renin-angiotensin system, the targets of common blood pressure medications, and endothelial cells, which line blood vessels.

Research on that theme is already underway at Emory. Malu Tansey is leading a large project funded by the National Institute on Aging ($3.4 million) with a similar title: “Inflammation and Renin-Angiotensin System Dysfunction as Risk Factors for Alzheimer’s Disease.” Co-investigators are Felicia Goldstein and Lary Walker at Emory and Christopher Norris at the University of Kentucky.

Both studies build on evidence that molecules that control blood pressure and inflammation also drive progression of Alzheimer’s disease, including work by Emory’s Whitney Wharton and Ihab Hajjar. They had found in an observational study that people who take medications targeting the renin-angiotensin system have a lower risk of progressing from mild cognitive impairment to Alzheimer’s.

Wharton is gearing up to test that idea more directly in an interventional study with the generic angiotensin receptor blocker telmisartan. This study is part of a Part the Cloud initiative supported by the Alzheimer’s Association.

Tansey’s project has started bearing fruit in an animal model of Alzheimer’s, according to this Keystone meeting report from Alzforum. Last summer, her graduate student Kathryn Macpherson described initial findings on the effects of an anti-inflammatory (anti-TNF) agent, which also has positive effects in a Parkinson’s model, and her plans to investigate the effects of high-sugar, high-fat diet.

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

Food deserts and cardiovascular risk

Heval Mohamed Kelli, MD got some attention at the American College of Cardiology meeting over the weekend with his work on food deserts — low-income areas distant from access to healthy food.

As Medscape summarized the results: “Atlantans living in disadvantaged areas where the nearest supermarket was a mile or more away were more likely to have hypertension or hyperlipidemia, smoke, be obese, and have higher levels of systemic inflammatory markers and stiffer arteries.”

Kelli_cover

Kelli at Clarkston Health Clinic, which Emory doctors helped establish in 2015. Clarkston is considered a “food desert”.

For more on Kelli’s journey from Syrian refugee to Clarkston, GA teenager to Emory cardiology researcher, check out this feature in Emory Magazine.

His research was conducted through the Emory Clinical Cardiovascular Research Institute, using information on 712 community participants from the META-Health study and 709 Emory/Georgia Tech employees from the Predictive Health study.

Three possibilities for further investigation:

*Income, education, race and geography are intertwined. “Whether lack of access to healthy foods, low income, or low education is driving these processes needs to be further studied,” Kelli and colleagues concluded.

*For detailed maps of food deserts, not just in Atlanta and/or determined using different criteria, the U.S. Department of Agriculture makes it possible.

*This Atlantic article makes the point that “when it comes to nutrition access, the focus should be on poverty, not grocery-store location.” You can lead people to the supermarket (or build one close to where they live), but you can’t make them eat a Mediterranean diet. Studies from Los Angeles showed that obesity increased more in some neighborhoods, even despite a ban on new fast food restaurants.

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When cardiac risk biomarkers will become really useful (and save money?)

The news is awash in studies of cholesterol-lowering statins and a much-anticipated (and expensive) class of drugs called PCSK9 inhibitors. Clinical trials show that now-generic (and cheap) statins reduce the risk of heart attack and stroke, although some patients report they can’t tolerate them. The data is still to come showing whether PCSK9 inhibitors have the same risk-lowering effect, as opposed to their effects on LDL cholesterol, which are robust.

When /if doctors have to start deciding who should take drugs that cost thousands of dollars a year and who shouldn’t, biomarkers may come in handy. How about a panel of markers like the one studied by Emory cardiologist Arshed Quyyumi, MD and colleagues?

At the recent American College of Cardiology meeting in Chicago, research fellow Salim Hayek, MD reported on a five-marker panel and how it could predict the risk of cardiovascular events (that is: death, heart attack, hospitalization for heart failure) in a group of patients who underwent cardiac catheterization at Emory hospitals.

The five biomarkers are: C-reactive protein (CRP, measures inflammation), suPAR (soluble urokinase-type plasminogen activator receptor or suPAR, predicts kidney disease), fibrin degradation products (FDP: blood coagulation), heat-shock protein-70 (HSP70, cellular stress) and troponin (hs-TnI, cardiac muscle damage). Data on three of these were published in 2013.

The Emory team keeps adding more biomarkers, and the ability of the accumulated information to add to what doctors can figure out easily — the Framingham score and its successors — becomes stronger.

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ACC 2016: Stem cell study sees improved heart failure outcomes

Patients with heart failure who received an experimental stem cell therapy experienced a reduced rate of death, hospitalization and unplanned clinic visits over the next year compared to a placebo group, according to results presented Monday at the American College of Cardiology meeting in Chicago.

The results of the ixCELL-DCM study were published online Monday by The Lancet. It was reportedly the largest cell therapy study done in patients with heart failure so far (58 treated vs 51 placebo).

Emory University School of Medicine investigators led by Arshed Quyyumi, MD, and their patients participated in the study, and Emory was one of the largest enrolling sites. Lead authors were Timothy Henry, MD of Cedars-Sinai Heart Institute in Los Angeles and Amit Patel, MD of the University of Utah.

“For the first time, a clinical trial has shown that administration of a cellular therapeutic results in an improvement in cardiac outcomes based on a prespecified analysis,” an editorial accompanying the paper in The Lancet says.

This study, which was sponsored by Vericel Corporation, was phase II, meaning that a larger phase III study will be needed before FDA approval. Read more

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ACC 2016: Elevated troponin linked to mental stress ischemia

Some people with heart disease experience a restriction of blood flow to the heart in response to psychological stress. Usually silent (not painful), the temporary restriction in blood flow, called ischemia, is an indicator of greater mortality risk.

Given the potential risks associated with stress-related ischemia in individuals with heart disease, it is essential to explore alternative approaches for managing stress and anxiety. While some individuals may turn to pharmaceutical medications, there is growing interest in the use of natural products from Orange County CBD to address these concerns. As research into the potential benefits of CBD continues to grow, it is becoming increasingly clear that Anxiety Medical Marijuana may offer a safe and effective way to manage stress and anxiety without the risks associated with some traditional medications. However, it is important to note that individuals with heart disease should always discuss the use of Orange County CBD or any other natural product with their healthcare provider before starting treatment, and try other options like cbd oils which can be beneficial as well. Should be given the medical go ahead to use cbd, you will find that there are many different options like 3.5g CBD Flower available to you, so you should be able to find one that you like and prefer over the rest.

Cardiologists at Emory University School of Medicine have discovered that people in this group tend to have higher levels of troponin — a protein whose increased presence in the blood that is a sign of recent damage or stress to the heart muscle– all the time, independently of whether they are experiencing stress or chest pain at that moment.

The results were presented Sunday by cardiology research fellow Muhammad Hammadah, MD at the American College of Cardiology meeting in Chicago, as part of the Young Investigator Awards competition. Hammadah works with Arshed Quyyumi, MD, and Viola Vaccarino, MD, PhD, and colleagues at the Emory Clinical Cardiovascular Research Institute.

“Elevated troponin levels in patients with coronary artery disease may be a sign that they are experiencing repeated ischemic events in everyday life, with either psychological or physical triggers,” Hammadah says.

Doctors test for troponin in the blood to tell whether someone has recently had a heart attack. But the levels seen in this study were lower than those used to diagnose a heart attack: less than a standard cutoff of 26 picograms per milliliter, in a range that only a high-sensitivity test for troponin could detect.

In a separate study, Emory investigators have shown that elevated troponin levels (especially: more than 10 pg/mL)  predict mortality risk over the next few years in patients undergoing cardiac catheterization, even in those without apparent coronary artery disease.

There is already a lot of information available for doctors about the significance of elevated troponin. It has even been detected at elevated levels after strenuous exercise in healthy individuals. One recent study suggested that low levels of troponin could be used to rule out heart attack for patients in the emergency department.

More information about the mental stress ischemia study: Read more

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Manipulating mouse genes to order, CRISPR or old-school

Just a follow-up to last week’s announcement from the Emory Transgenic Mouse and Gene Targeting core that they are offering CRISPR/Cas9 gene editing for mice. Using CRISPR/Cas9 to produce genetically altered mice is a

Knockout_mice

Gene targeting – the 20th century way

substantial advance over the old way of doing knockouts and other manipulations (which itself won a Nobel Prize in 2007), mainly because it’s faster and easier.

To appreciate the difference, consider that the old way involves introducing DNA into mouse embryonic stem cells, and then selecting for the rare cells that take up and incorporate the DNA in the right way. Then the ES cells have to be injected into a blastocyst, followed by mouse breeding to “go germline.”

With CRISPR/Cas9, it’s possible to inject pieces of RNA that target the desired genetic changes, straight into a one-cell stage mouse embryo. Not every embryo has all the right changes, but the frequency is high enough to inject and screen. As this review explains, it’s possible to introduce mutations into three genes at once and get mice quickly, rather than make each one separately and then breed the mice together, which can take many months.

Also, because of the need for drug selection, the targeting construct in old-school gene targeting has to be a blunt instrument. That can make it hard to make subtle changes to a gene — like introduce point mutations corresponding to natural variations linked with human disease — without taking a sledgehammer to the entire gene locus. CRISPR/Cas9 takes care of that problem.

Despite the advantages of this technology, three things to keep in mind:

*Many genetically altered mice are already available “off the shelf” as part of the International Knockout Mouse/Mouse Phenotyping Consortium.

*Emory’s Mouse Core has been working with the company Ingenious Gene Targeting, and has been out-sourcing some of the tedious aspects of old-school gene targeting in mice to Ingenious, starting last year. Technicians there can generate a dazzling array of conditional knockouts. If you want your favorite gene to flip around and produce a fluorescent protein when you give the mice an antibiotic, but only in some cells — Ingenious can do that. Old school is actually still the way to go for fancy stuff like this.

*Jackson Labs in Maine also works with Emory, offering similar services, and offers a guarantee. Read more

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