Saliva-based SARS-CoV-2 antibody testing

As the Atlanta area recovers from Zeta, we’d like to highlight this Journal of Clinical Microbiology paper about saliva-based SARS-CoV-2 antibody testing. It was a collaboration between the Hope Clinic and investigators at Johns Hopkins, led by epidemiologist Christopher Heaney. Infectious disease specialists Matthew Collins, Nadine Rouphael and several colleagues from Emory are co-authors. They organized the collection of saliva and blood samples from Emory COVID-19 patients at several stages: being tested, hospitalized, and recovered. Read more

Peeling away pancreatic cancers' defenses

A combination immunotherapy approach that gets through pancreatic cancers’ extra Read more

Immune cell activation in severe COVID-19 resembles lupus

In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of B cells, resembling acute flares in systemic lupus erythematosus (SLE), an autoimmune disease. The findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. It also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes. The results were published online on Oct. Read more

Department of Pharmacology and Chemical Biology

The sweet side of Alzheimer’s proteomics

The Alzheimer’s field has been in a “back to the basics” mode lately. Much research has focused on beta-amyloid, the toxic protein fragment that accumulates in plaques in the brain. Yet drugs that target beta-amyloid have mostly been disappointing in clinical trials.

To broaden scope and gain new insights into the biology of Alzheimer’s, Emory investigators have been making large-scale efforts to catalog alterations of brain proteins. One recent example: Nick Seyfried and Erik Johnson’s enormous collection of proteomics data, published this spring in Nature Medicine. Another can be seen in the systematic mapping of N-glycosylation, just published in Science Advances by pharmacologist Lian Li and colleagues.

“It is very exciting to see, for the first time, the landscape of protein N-glycosylation changes in Alzheimer’s brain,” Li says. “Our results suggest that the N-glycosylation changes may contribute to brain malfunction in Alzheimer’s patients.  We believe that targeting N-glycosylation may provide a new opportunity to help combat this devastating dementia.”

Read more

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Traynelis lead researcher on CureGRIN/Chan Zuckerberg award

Congratulations to the CureGRIN Foundation, which was recently awarded a capacity-building grant from the Chan Zuckerberg Initiative’s Rare as One Network. The Chan Zuckerberg Initiative is giving 30 patient advocacy groups such as CureGRIN $450,000 each over two years.

CureGRIN works closely with Emory pharmacologist Stephen Traynelis, who has been investigating rare genetic disorders affecting NMDA receptors, which play key roles in memory, learning and neuronal development. When NMDA receptor function is perturbed by mutations, symptoms appear in infancy or early childhood, usually including epilepsy and developmental delay.

For the grant, Traynelis is named as the lead researcher for the CureGRIN Foundation, with Tim Benke of Children’s Hospital Colorado as lead clinician. Traynelis is director of the Center for Functional Evaluation of Rare Variants, which hosted a gathering at Emory Conference Center that brought together several GRIN-oriented patient advocacy groups in September 2019.

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Mapping the cancer genome wilderness

A huge cancer genome project has highlighted how DNA that doesn’t code for proteins is still important for keeping our cells on track.

The Pan-Cancer Analysis of Whole Genomes analyzed more than 2,600 tumors from 38 tissues, looking for causative mutations and patterns. Previous work had concentrated on the regions of the genome that code for proteins, but a significant proportion of cancer patients’ tumors don’t carry known “driver” (causative) mutations in protein-coding regions. So this project went out into what used to be called “junk DNA” or the “dark matter” of the genome.

Emory bioinformatics postdoc Matthew Reyna is the first author of one of 23 papers on the PCAWG project, published Feb. 5 in the Nature family of journals. His paper in Nature Communications looks at mutations in non-coding regions of the genome in tumors, analyzing which biological processes are affected.

Some of these were mutations in the promoters of genes encoding well-known cancer suppressors such as p53, but the project also identified new genes containing cancer-driving mutations. A promoter is the stretch of DNA that tells the cell “make RNA copies starting here”.

Reyna contributed to the project while he was at Princeton, working with Benjamin Raphael, and at Emory as well. More recently, he’s been investigating protein-protein interactions with Haian Fu, Andrey Ivanov and others as part of the Cancer Target Discovery and Development (CTD2) project.

Posted on by Quinn Eastman in Cancer Leave a comment

GRIN families join together for neuroscience

Editor’s note: This post was a collaboration with MMG graduate student Megan Hockman.

They were brought together by their children’s epilepsies, and by rapid advances in genetic sequencing. Only a few years ago, these families would have been isolated, left to deal with their children’s seizures and neurological problems on their own. Now, they’ve organized themselves and are shaping the future of research.

Agonist binding domains of NMDA receptors, where several disease-causing mutations can be found. Adapted from Swanger et al, AJHG (2016).

In mid-September, parents of children affected by variations in GRIN genes gathered at Emory Conference Center to meet with scientists to discuss current research. GRIN disorders occur because of mutations in genes encoding NMDA receptors, which play key roles in memory, learning and neuronal development. NMDA receptors are a type of receptor for glutamate, the main excitatory neurotransmitter in the brain. The receptors themselves are encoded by multiple genes and assemble into tetramers. When their function is altered by mutations in one of these genes, symptoms appear in infancy or early childhood, usually including epilepsy and developmental delay.

The conference was the first time several patient advocacy groups oriented around GRIN-related disorders had met together, says Denise Rehner, president of the CureGRIN Foundation and mother of an affected child. For parents, this was an opportunity to connect with each other and advocacy groups, and to interact with scientists. For researchers, it was a chance to hear from those who are being impacted by their studies, and to discuss better ways to share data.

“We got a chance to explain to all the stakeholders – patient groups, foundations, companies – exactly what we do,” said Emory neuroscientist and conference organizer Stephen Traynelis, director of the Center for Functional Evaluation of Rare Variants. Traynelis and colleague Hongjie Yuan have been tracking the direct impacts of mutations on the function of the NMDA receptor. In doing so, they plan work with clinicians to compile registries, linking specific functional data to patient symptoms.

In addition to understanding underlying mechanisms and outcomes of GRIN disorders, researchers want to figure out how to treat affected children with existing drugs. Several options exist for targeting NMDA receptors, such as dextromethorphan (a cough suppressant) or memantine, approved for symptoms of Alzheimer’s. Traynelis and Yuan previously collaborated with the Undiagnosed Disease Program (now the Undiagnosed Disease Network) at the National Institutes of Health to investigate memantine as a treatment for a child with a GRIN2A mutation, showing that the drug could reduce seizure burden in one patient. Read more

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