Simpler, more portable ECGs: Emory experts hosting computing challenge

Emory biomedical informatics specialists are hosting an international computing contest to support simpler, more potable electrocardiogram Read more

First (and massive) whole-genome study of IBD in African Americans

In African Americans, the genetic risk landscape for inflammatory bowel disease (IBD) is very different from that of people with European ancestry, according to results of the first whole-genome study of IBD in African Americans. The authors say that future clinical research on IBD needs to take ancestry into account. Findings of the multi-center study, which analyzed the whole genomes of more than 1,700 affected individuals with Crohn’s disease and ulcerative colitis and more than Read more

Emory researchers SNARE new Alzheimer’s targets

Diving deep into Alzheimer’s data sets, a recent Emory Brain Health Center paper in Nature Genetics spots several new potential therapeutic targets, only one of which had been previous linked to Alzheimer’s. The Emory analysis was highlighted by the Alzheimer’s site Alzforum, gathering several positive comments from other researchers. Thomas Wingo, MD Lead author Thomas Wingo and his team -- wife Aliza Wingo is first author – identified the targets by taking a new approach: tracing Read more

Immunology

First (and massive) whole-genome study of IBD in African Americans

In African Americans, the genetic risk landscape for inflammatory bowel disease (IBD) is very different from that of people with European ancestry, according to results of the first whole-genome study of IBD in African Americans. The authors say that future clinical research on IBD needs to take ancestry into account.

Findings of the multi-center study, which analyzed the whole genomes of more than 1,700 affected individuals with Crohn’s disease and ulcerative colitis and more than 1,600 controls, were published on February 17 in the American Journal of Human Genetics.

As part of their analysis, the researchers developed an algorithm that corrects for ancestry when calculating an IBD polygenic risk score. Polygenic risk scores are tools for calculating gene-based risk for a disease, which are used for IBD as well as other complex conditions such as coronary artery disease.

“Even though the disease destination looks the same, the populations look very different, in terms of what specific genes contribute to risk for IBD,” says lead author Subra Kugathasan, MD. “It shows that you can’t develop a polygenic risk score based on one population and apply it to another.”

Kugathasan is scientific director of the pediatric IBD program and director of the Children’s Center for Transplantation and Immune-mediated Disorders at Children’s Healthcare of Atlanta, as well as Marcus professor of pediatrics and human genetics at Emory University School of Medicine.

The first author of the paper is geneticist Hari Somineni, PhD, who earned his doctorate working with Kugathasan at Emory, and is now working at Goldfinch Bio in Massachusetts.

The primary sites to recruit study participants were Emory, Cedars-Sinai and Rutgers, along with Johns Hopkins and Washington University at Saint Louis. Along with Kugathasan, the co-senior authors and co-organizers of the study were Steven Brant, MD from Rutgers and Dermot McGovern, MD, PhD from Cedars-Sinai.

“One of our goals in treating IBD is to move toward a more personalized approach,” says McGovern, the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics at Cedars-Sinai. “Deciphering the genetic architecture is an important part of this effort. Studies such as this one are vital to ensure that diverse populations, including African-Americans, benefit from the tremendous advances promised by genomic medicine.”

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Strengthening SARS-CoV-2 genomic surveillance: support from CDC, private foundations

As part of an effort to strengthen genomic surveillance for emerging strains of SARS-CoV-2, the Centers for Disease Control and Prevention (CDC) has awarded a contract to Emory University researchers to characterize viral variants circulating in Georgia.

The two-year contract is part of the SPHERES (SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology and Surveillance) initiative, with roughly $620,000 in total costs. The principal investigator is Anne Piantadosi, MD, PhD, assistant professor of pathology and laboratory medicine, with co-investigator Mehul Suthar, PhD, assistant professor of pediatrics (infectious diseases).

Both Piantadosi and Suthar are affiliated with Emory University School of Medicine and Emory Vaccine Center. Additional Emory partners include assistant professor of medicine Ahmed Babiker, MBBS, assistant professor of medicine Jesse Waggoner, MD and assistant professor of biology Katia Koelle, PhD.

“We are analyzing SARS-CoV-2 genomes from patients in Georgia to understand the timing and source of virus introduction into our community,” Piantadosi says. “We want to know whether there have been population-level changes in the rates of viral spread, and whether there are associations between viral genotype, viral phenotype in vitro, and clinical phenotype or clinical outcome.”

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Combo approach vs drug-resistant fungus

Before 2020 and the COVID-19 pandemic, concern among infectious disease specialists was rising about Candida auris, an emerging fungal pathogen that is often drug-resistant and difficult to eradicate from hospitals.

CDC image of Candida auris

Many people know Candida can cause mouth or vaginal infections and diaper rashes. According to the CDC, Candida also can cause invasive infections in the bloodstream, particularly in hospital or nursing home patients with weakened immune systems. About 30 percent of patients with an invasive Candida infection die – and C. auris is just one particularly hardy variety.

Emory Antibiotic Resistance Center director David Weiss and colleagues have identified a combination of existing antifungal drugs (micafungin and amphotericin B) with enhanced activity against C. auris when used together. The results – in vitro only, so far — were published in a letter to The Lancet Microbe. Postdoctoral fellow Siddharth Jaggavarapu was the first author. Weiss reports his team continues to investigate combination approaches against C. auris.

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Engineered “stealth bomber” virus could be new weapon against metastatic cancer

Many cancer researchers can claim to have devised “smart bombs.” What has been missing is the stealth bomber – a delivery system that can slip through the body’s radar defenses. 

Oncolytic viruses, or viruses that preferentially kill cancer cells, have been discussed and tested for decades. An oncolytic virus against melanoma was approved by the FDA in 2015. But against metastatic cancers, they’ve always faced an overwhelming barrier: the human immune system, which quickly captures viruses injected into the blood and sends them to the liver, the body’s garbage disposal.

Researchers at Emory and Case Western Reserve have now circumvented that barrier. They’ve re-engineered human adenovirus, so that the virus is not easily caught by parts of the innate immune system.

The re-engineering makes it possible to inject the virus into the blood, without arousing a massive inflammatory reaction.

A cryo-electron microscopy structure of the virus and its ability to eliminate disseminated tumors in mice were reported on November 25 in Science Translational Medicine.

“The innate immune system is quite efficient at sending viruses to the liver when they are delivered intravenously,” says lead author Dmitry Shayakhmetov, PhD. “For this reason, most oncolytic viruses are delivered directly into the tumor, without affecting metastases. In contrast, we think it will be possible to deliver our modified virus systemically at doses high enough to suppress tumor growth — without triggering life-threatening systemic toxicities.”

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Don’t go slippery on me, tRNA

RNA can both carry genetic information and catalyze chemical reactions, but it’s too wobbly to accurately read the genetic code by itself. Enzymatic modifications of transfer RNAs – the adaptors that implement the genetic code by connecting messenger RNA to protein – are important to stiffen and constrain their interactions.

Biochemist Christine Dunham’s lab has a recent paper in eLife showing a modification on a proline tRNA prevents the tRNA and mRNA from slipping out of frame. The basics of these interactions were laid out in the 1980s, but the Dunham lab’s structures provide a comprehensive picture with mechanistic insights.

The mRNA code for proline is CCC – all the nucleotides are the same — so it is susceptible to frameshifting.

The paper includes videos that virtually unwrap the RNA interactions. The X-ray crystal structures indicate that tRNA methylation – a relatively small bump — at position 37 influences interactions between the tRNA and the ribosome.

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Muscle cell boundaries: some assembly required

With cold weather approaching, many are digging out old jackets to find that the zippers don’t function as well as they used to. This is a good way to understand disruptions of muscle cell attachment studied by Emory cell biologist Guy Benian’s lab. 

Benian and colleagues have a paper on muscle cell biology in Nature Communications this week. In the worm C. elegans, they show how mutations cause junctions between muscle cells, which normally look like well-aligned zippers under the microscope, to either not form, or weaken and unravel. As a result, the mutant worms’ snake-like locomotion is impaired.

Zipper-like muscle cell boundaries are altered in pix-1 mutants

“This is yet another example in which research using the model genetic organism C. elegans has led to a new insight applicable to all animals, including humans,” Benian says. “Research on this organism has led to crucial advances in our understanding about development, cell death, aging and longevity, RNAi, microRNAs, epigenetics — and muscle.”

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Detecting heart failure via wearable devices

Cardiology researchers have been eagerly taking up consumer electronic devices that include pulse oximeters. Being able to conveniently measure the level of oxygen in someone’s blood is a useful tool, whether one is interested in sleep apnea or COVID-19.

The news that the new Apple Watch includes a pulse oximeter prompted Lab Land to check in with Amit Shah, an Emory cardiologist who has been experimenting with similar devices to discriminate patients with heart failure from those with other conditions.

Shah, together with Shamim Nemati, now at UCSD, and bioinformatics chair Gari Clifford recently published a pilot study on detecting heart failure using the Samsung Simband. The Simband was a prototype device that didn’t make it to the consumer market, but it carried sensors for optical detection of blood volume changes (photoplethysmography), like on the Apple Watch. 

Heart failure causes symptoms such as shortness of breath and leg swelling, but other conditions such as anemia or lung diseases can appear similarly. The idea was to help discriminate people who might need an examination by echocardiogram (cardiac ultrasound).

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Several ways to survey for SARS-CoV-2 exposure

How many people out there have been exposed to SARS-CoV-2? It’s a tricky question, once you think about all the people who have experienced COVID-19 symptoms over the last several months, but didn’t go to the hospital. And there’s a murkier penumbra of people who may have fended off the virus with a minor immune skirmish.

A recent Emerging Infectious Diseases paper from Emory investigators includes antibody tests on a group of more than 100 adults in the Atlanta area who experienced mild flu-like symptoms this spring, but couldn’t get tested for SARS-CoV-2 itself.

A sizable fraction (22 to 48 percent, depending on when they provided blood samples) had elevated levels of IgM against the coronavirus. IgM is the “rookie” antibody produced when the immune system is first encountering something, as opposed to the more seasoned IgG, which appears later in an immune response and tended to rise only in people who were hospitalized. The Emory authors came to a conclusion that others are also reaching:

“Examining IgM and IgG against multiple SARS-CoV-2–related antigens may thus better inform natural history and vaccine studies than any one antibody.”

To answer these kinds of questions more comprehensively, investigators will need to go broader. For example, this week the American Red Cross published data on what proportion of its blood donors have antibodies against SARS-CoV-2. About 3 percent of first-time donors did, using their criteria.

For big answers, we can look to studies such as Emory’s COVID-Vu, a nationwide population-based study using antibody and virus tests taken at home. Rollins School of Public Health researchers received a $6.6 million grant to launch the study this summer. This type of study is designed to cover everyone, whether they were sick or not.

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For genetically altered mice/rats, freeze and recharge

With a pandemic threatening the health and safety of Emory researchers in March 2020, university leadership made the difficult decision to ramp down some types of research. For investigators that use laboratory mice or rats in their research, this posed a significant challenge.

How could investigators maintain valuable, often unique, lines of genetically engineered animals for future research? The Mouse Transgenic and Gene Targeting Core (TMF) had a solution: cryopreservation. Animals’ sperm — and occasionally, embryos – can be carefully preserved in cold-resistant straws and stored in liquid nitrogen.

“Cryopreservation is a reliable and efficient method for archiving and distributing genetically engineered mouse lines,” says Karolina Piotrowska-Nitsche, PhD, director of the Core.

The TMF is located on the ground floor of the Emory Health Sciences Research Building and provides a suite of services related to transgenics and gene editing, working with tools such as CRISPR/Cas9 to make subtle or complex changes in the DNA of living animals.

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Georgia survey on COVID-19 testing/vaccination shows group differences

Public health experts stress that adequate representation of Black and Latinx people in COVID-19 vaccine studies is a priority. Given how COVID-19 is impacting vulnerable communities, acceptance of a future vaccine – whenever it may become available – is important. A recent article in the Atlanta Journal Constitution highlights how this issue is playing out in Georgia, given the legacy of lack of trust in biomedical research.

“The issue of minority participation in clinical trials is not just in vaccines, it really is in every clinical trial and the point is that the population that is most impacted and most affected needs to be represented in trials,” Emory’s Carlos del Rio said at a media briefing last week.

In a Sunday Op-Ed in the AJC, emergency physician Monique Smith called attention to the disparities in COVID-19 testing and follow-up. In the communities she serves, it is not just a challenge to get a test but to also understand what the results mean, or what to do while waiting for the results, she says.

Lab Land can add some data to that – a survey conducted by neurologist William Hu and colleagues in early August on attitudes toward COVID-19 testing and vaccination among Georgia residents. Non-Hispanic white respondents were more likely than Black/African-American respondents to recommend their loved ones to participate in a COVID-19 clinical trial or be vaccinated after FDA approval.

Green = Black/African-Americans, Clear = non-Hispanic white

From August survey data

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