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
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Wound-healing intestinal bacteria: like shrubs after a forest fire

In injured mouse intestines, specific types of bacteria step forward to promote healing, Emory scientists have found. One oxygen-shy type of bacteria that grows in the wound-healing environment, Akkermansia muciniphila, has already attracted attention for its relative scarcity in both animal and human obesity.

NMicro

An intestinal wound brings bacteria (red) into contact with epithelial cells (green). The bacteria can provide signals that promote healing, if they are the right kind.

The findings emphasize how the intestinal microbiome changes locally in response to injury and even helps repair breaches. The researchers suggest that some of these microbes could be exploited as treatments for conditions such as inflammatory bowel disease.

The results were published on January 27 in Nature Microbiology. Researchers took samples of DNA from the colon tissue of mice after they underwent colon biopsies. They used DNA sequencing to determine what types of bacteria were present.

“This is a situation resembling recovery after a forest fire,” says Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. “Once the trees are gone, there is an orderly succession of grasses and shrubs, before the reconstitution of the mature forest. Similarly, in the damaged gut, we see that certain kinds of bacteria bloom, contribute to wound healing, and then later dissipate as the wound repairs.” Read more

Posted on February 9, 2016 by Quinn Eastman in Immunology, Uncategorized Leave a comment

Oxidative stress ain’t about free radicals, it’s about sulfur

This recent paper in Circulation, from Arshed Quyyumi and colleagues at the Emory Clinical Cardiovascular Research Institute, can be seen as a culmination of, even vindication for,  Dean Jones’ ideas about redox biology.

Let’s back up a bit. Fruit juices, herbal teas, yogurts, even cookies are advertised as containing antioxidants, which could potentially fight aging. This goes back to Denham Harman and the free radical theory of aging. [I attempted to explain this several years ago in Emory Medicine.]

We now know that free radicals, in the form of reactive oxygen species, can sometimes be good, even essential for life. So antioxidants that soak up free radicals to relieve you of oxidative stress: that doesn’t seem to work.

Dean Jones, who is director of Emory’s Clinical Biomarkers laboratory, has been an advocate for a different way of looking at oxidative stress. That is, instead of seeing cells as big bags of redox-sensitive chemicals, look at cellular compartments. Look at particular antioxidant proteins and sulfur-containing antioxidant molecules such as glutathione and cysteine.

That’s what the Circulation paper does. Mining the Emory Cardiovascular Biobank, Quyyumi’s team shows that patients with coronary artery disease have a risk of mortality that is connected to the ratio of glutathione to cystine (the oxidized form of the amino acid cysteine).

How this ratio might fit in with other biomarkers of cardiovascular risk (such as CRP, suPAR, PCSK9, more complicated combinations and gene expression profiles, even more links here) and be implemented clinically are still unfolding.

Posted on February 5, 2016 by Quinn Eastman in Heart Leave a comment

When genes forget to forget

In ancient Greek mythology, the souls of the dead were made to drink from the river Lethe, so that they would forget their past lives. Something analogous happens to genes at the very beginning of life. Right after fertilization, the embryo instructs them to forget what it was like in the egg or sperm where they had come from.

This is part of the “maternal-to-zygote transition”: much of the epigenetic information carried on and around the DNA is wiped clean, so that the embryo can start from a clean slate.

Developmental biologist Lewis Wolpert once said: “It is not birth, marriage or death which is
the most important time in your life, but gastrulation,” referring to when the early embryo separates into layers of cells that eventually make up all the organs. Well, the MZT, which occurs first, comes pretty close in importance.

When this process of epigenetic reprogramming is disrupted, the consequences are often lethal. Emory cell biologists David Katz and Jadiel Wasson discovered that when mouse eggs are missing an enzyme that is critical for the MZT, on the rare instances when the mice survive to adulthood, they display odd repetitive behaviors. Read more

Posted on February 3, 2016 by Quinn Eastman in Neuro Leave a comment

Proteomics making fantastic routine

Much of basic biomedical research concerns proteins. The enzymes that keep cells running, the regulators and receptors that control what our cells do, the antibodies that defend us against invaders — all of these are proteins.

That means every day, scientists are asking questions like:

What’s happening to my favorite protein? Is there more or less of it in this sample? What other proteins work with it or stick to it?

That’s where a proteomics core facility comes in. Given a mixture of hundreds or even thousands of proteins, proteomics specialists can separate, identify and quantify them.Proteomics1smaller

Researchers in the areas of Alzheimer’s disease, cancer metabolism, schizophrenia and vaccines all make use of Emory’s proteomics core facility. It was key to the Alzheimer’s Disease Research Center’s 2013 discovery of a new form of Alzheimer’s disease protein pathology.

Director Nick Seyfried reports that the core has acquired close to $3 million in sophisticated mass spectrometry equipment in the last few years. The Emory Integrated Proteomics Core, one of the Emory Integrated Core Facilities, is supported in part by the Winship Cancer Institute, the Atlanta Clinical and Translational Science Institute, and a recently renewed grant for ENNCF (Emory Neurosciences NINDS Core Facilities).

Protein mass spectrometry is like Wonkavision

There’s a scene in both the 1971 and 2005 film adaptations of Roald Dahl’s Charlie and the Chocolate Factory, in which a chocolate bar is separated into millions of tiny pieces and sent flying across a clean room. Protein mass spectrometry resembles the first part of this process. Read more

Posted on February 1, 2016 by Quinn Eastman in Neuro Leave a comment

Improving long-term outcomes after kidney transplant

Twenty years of research and you start to improve outcomes for transplant patients.

The Nature paper from Chris Larsen and Tom Pearson on “costimulation blockers” and their ability to head off graft rejection in rodents first appeared in 1996.

Almost 20 years later, a seven-year study of kidney transplant recipients has shown that the drug belatacept, a costimulation blocker based on Larsen and Pearson’s research, has a better record of patient and organ survival than a calcineurin inhibitor, previously the standard of care.

Kidney transplant recipients need to take drugs to prevent their immune systems from rejecting their new organs, but the drugs themselves can cause problems. Long-term use of calcineurin inhibitors, such as tacrolimus, can damage the transplanted kidneys and lead to cardiovascular disease and diabetes.

In the accompanying video, Larsen - now dean of Emory University School of Medicine – and Pearson - executive director of Emory Transplant Center – explain.

Belatacept was approved by the FDA in 2011 and is produced by Bristol Myers Squibb. Results from the BENEFIT study of belatacept, led by Larsen and UCSF transplant specialist Flavio Vincenti, were published in the Jan. 28 issue of the New England Journal of Medicine.

To go with the paper, NEJM has an editorial with some revealing statistics (more than 14,000 of the 101,000 patients listed for kidney transplantation are waiting for a repeat transplant) and a explanatory video. MedPage Today has an interview with Larsen, and HealthDay has a nice discussion of the issues surrounding post-transplant drugs. Read more

Posted on January 28, 2016 by Quinn Eastman in Immunology Leave a comment

Neurons dominate GDBBS contest-winning images

Lab Land’s editor enjoyed talking with several students about their work at the GDBBS Student Research Symposium last week. Neurons dominate the three contest-winning images. The Integrated Cellular Imaging core facility judged the winners. From left to right:

ContestComposite

1st Place: Stephanie Pollitt, Neuroscience

2nd Place: Amanda York, Biochemistry, Cell and Developmental Biology

3rd Place: Jadiel Wasson, Biochemistry, Cell and Developmental Biology

Larger versions and explanations below.

Read more

Posted on January 20, 2016 by Quinn Eastman in Neuro Leave a comment

Rescuing existing antibiotics with adjuvants

One of the speakers at Thursday’s Antibiotic Resistance Center symposium, Gerald Wright from McMaster University, made the case for fighting antibiotic resistance by combining known antibiotics with non-antibiotic drugs that are used to treat other conditions, which he called adjuvants.

As an example, he cited this paper, in which his lab showed that loperamide, known commercially as the anti-diarrheal Immodium, can make bacteria sensitive to tetracycline-type antibiotics.

Wright said that other commercial drugs and compounds in pharmaceutical companies’ libraries could have similar synergistic effects when combined with existing antibiotics. Most drug-like compounds aimed at human physiology follow “Lipinski’s rule of five“, but the same rules don’t apply to bacteria, he said. What might be a more rewarding place to look for more anti-bacterial compounds? Natural products from fungi and plants, Wright proposed.

“I made a little fist-pump when he said that,” says Emory ethnobotanist Cassandra Quave, whose laboratory specializing in looking for anti-bacterial activities in medicinal plants.

Medical thnobotanist Cassandra Quave collecting plant specimens in Italy.

Medical ethnobotanist Cassandra Quave collecting plant specimens in Italy

Indeed, many of the points he made on strategies to overcome antibiotic resistance could apply to Quave’s approach. She and her colleagues have been investigating compounds that can disrupt biofilms, thus enhancing antibiotic activity. More at eScienceCommons and at her lab’s site.

Posted on January 15, 2016 by Quinn Eastman in Uncategorized Leave a comment

Galectins defend against bacterial wolves in sheeps’ clothing

To prevent auto-immune attack, our bodies avoid making antibodies against molecules found on our own cells. That leaves gaps in our immune defenses bacteria could exploit. Some of those gaps are filled by galectins, a family of proteins whose anti-bacterial properties were identified by Emory scientists.

In the accompanying video, Sean Stowell, MD, PhD and colleagues explain how galectins can be compared to sheep dogs, which are vigilant in protecting our cells (sheep) against bacteria that may try to disguise themselves (wolves).

The video was produced to showcase the breadth of research being conducted within Emory’s Antibiotic Resistance Center. Because of their ability to selectively target some kinds of bacteria, galectins could potentially be used as antibiotics to treat infections without wiping out all the bacteria in the body. Read more

Posted on January 15, 2016 by Quinn Eastman in Immunology Leave a comment

Sidestepping the placebo effect when studying depression

Research on depression must deal with a major obstacle: the placebo effect. This is the observation that patients improve in response to the sugar pills given as controls in clinical studies.

Clinical trial designers can incorporate various clever strategies to minimize the placebo effect, which is actually comprised of several statistical and psychological factors. Investigators can try to enhance, dissect or even “harness” them. [A recent piece in the New York Times from Jo Marchant focuses on the placebo effect in studies of pain relief.]

Emory psychiatrist Andrew Miller and his team have been developing a different approach over the last few years: studying symptoms of depression in people who are being treated for something else. This allows them to sidestep, at least partially, the cultural construct of depression, from William Styron to Peter Kramer to direct-to-consumer television ads.

Interferon alpha, a treatment used against hepatitis C virus infection and some forms of cancer, is a protein produced by the immune system that spurs inflammation. It also can induce symptoms of depression, such as fatigue and malaise. There are some slight differences with psychiatric depression, which Miller’s team describes here (less guilt!), but they conclude that there is a “high degree of overlap.”

Miller and his colleagues, including Jennifer Felger and Ebrahim Haroon, have documented how interferon-alpha-induced inflammation affects the brains of hepatitis C and cancer patients in several papers. That research, in turn, informs their more recent fruitful investigations of inflammation in the context of major depression. More on that soon.

Posted on January 13, 2016 by Quinn Eastman in Immunology, Neuro Leave a comment

NINDS director: neuroscience now largest ‘bucket of money’

On Friday, NINDS director Walter Koroshetz made an interesting remark in a lecture to Emory’s Department of Neurology. He said that in the 2016 National Institues of Health budget, neuroscience is now the largest “bucket of money,” especially with the recent boost in funding for Alzheimer’s research. That’s larger than the bucket for cancer. To be sure, biomedical research in general got a boost from Congress, with the NIH receiving its largest increase in a decade, and cancer is still a big deal!

Koroshetz explained that neuroscience research is spread out among NINDS (National Institute for Neurological Disorders and Stroke), NIMH (National Institute of Mental Health), NIDA (National Institute for Drug Abuse) and several others, while cancer research is concentrated at the National Cancer Institute. [Here’s some official category tracking that the NIH does – his breakdown checks out.]

Koroshetz highlighted a project from Dieter Jaeger and Garret Stanley that is part of the White House’s BRAIN Initiative focused on mapping brain circuits and connectivity. He also noted NINDS’s efforts in promoting translational research, since pharmaceutical companies were frustrated by repeated failures in the 1990s with difficult areas such as stroke, and the R35 mechanism for funding “outstanding investigators” for up to eight years continuously.

Posted on January 12, 2016 by Quinn Eastman in Neuro 2 Comments
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