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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Jeremy Boss

B cells off the rails early in lupus

New research on the autoimmune disease systemic lupus erythematosus (SLE) provides hints to the origins of the puzzling disorder. The results are published in Nature Immunology.

In people with SLE, their B cells – part of the immune system – are abnormally activated. That makes them produce antibodies that react against their own tissues, causing a variety of symptoms, such as fatigue, joint pain (the IUD placement in Forest Hills are the best ones to cure these kind of pain), skin rashes and kidney problems.

Scientists at Emory University School of Medicine could discern that in people with SLE, signals driving expansion and activation are present at an earlier stage of B cell differentiation than previously appreciated. They identified patterns of gene activity that could be used as biomarkers for disease development.

Activation can be observed at an early stage of B cell differentiation: resting naive cells (pink ellipse). Adapted from Jenks et al Immunity (2018).

“Our data indicate a disease signature across all cell subsets, and importantly on mature resting B cells, suggesting that such cells may have been exposed to disease-inducing signals,” the authors write.

The paper reflects a collaboration between the laboratories of Jeremy Boss, PhD, chairman of microbiology and immunology, and Ignacio (Iñaki) Sanz, MD, head of the division of rheumatology in the Department of Medicine. Sanz, recipient of the 2019 Lupus Insight Prize from the Lupus Research Alliance, is director of the Lowance Center for Human Immunology and a Georgia Research Alliance Eminent Scholar. The first author is Christopher Scharer, PhD, assistant professor of microbiology and immunology.

The researchers studied blood samples from 9 African American women with SLE and 12 healthy controls. They first sorted the B cells into subsets, and then looked at the DNA in the women’s B cells, analyzing the patterns of gene activity. Sanz’s team had previously observed that people with SLE have an expansion of “activated naïve” and DN2 B cells, especially during flares, periods when their symptoms are worse. Read more

Posted on July 1, 2019 by Quinn Eastman in Immunology Leave a comment

Antibody production: an endurance sport

Antibodies defend us against infections, so they often get described as weapons. And the cells that produce them could be weapon factories?. To understand recent research from immunologist Jerry Boss’s lab, a more appropriate metaphor is the distinction between sprinting and long-distance running.

Graduate student Madeline Price in Boss’s lab has been investigating how antibody-producing cells use glucose – the simple sugar– and how the cells’ patterns of gene activity reflect that usage. Cells can use glycolysis, which is inefficient but fast, analogous to sprinting, or oxidative phosphorylation, generating much more energy overall, more like long distance running.

As Boss and Price point out:

Immunology + Molecular Pathogenesis graduate student Madeline Price

Glycolytic metabolism produces 2 molecules of ATP per molecule of glucose, while oxidative phosphorylation produces 36 molecules of ATP from the same starting glucose molecule. Where oxidative phosphorylation generates more energy from ATP, glycolysis generates metabolic intermediates that are also useful for rapid cellular proliferation.

In their recent paper in Cell Reports, they lay out what happens to B cells, which can go on to become antibody secreting cells (ASCs), after an initial encounter with bacteria. The B cells first proliferate and upregulate both glycolysis and oxidative phosphorylation. However, upon differentiating, the cells shift their preference to oxidative phosphorylation. Read more

Posted on June 19, 2018 by Quinn Eastman in Immunology Leave a comment

Plasma cells, antibody factories

Immune cells that serve as antibody production factories, also known as plasma cells, are the focus of a recent Nature Immunology paper from Jeremy Boss and colleagues.

Plasma cells also appear in Ali Ellebedy and Rafi Ahmed’s recent paper on the precursors of memory B cells and Eun Lee’s work on long-lived antibody-producing cells. In addition, plasma cells appear prominently in Larry Boise’s studies of myeloma, because myeloma cancer cells are thought to come from plasma cells and have a similar biology.B cell methylation

The Boss lab’s paper focuses on patterns of methylation, modifications of DNA that usually help turn genes off. In comparison with resting B cells, plasma cells need to turn on lots of genes, so their DNA methylation level goes down when differentiation occurs (see graph). PC = plasma cells, PB = plasmablasts. DNAme indicates the extent of DNA methylation. Read more

Posted on August 25, 2016 by Quinn Eastman in Immunology Leave a comment

Risk triangle: immune gene, insecticide, Parkinson’s

Genetic variation and exposure to pesticides both appear to affect risk for Parkinson’s disease. A new study has found a connection between these two risk factors, in a way that highlights a role for immune responses in progression of the disease.

The results are published in the inaugural issue of NPJ Parkinson’s Disease.

The findings implicate a type of pesticide called pyrethroids, which are found in the majority of commercial household insecticides, and are being used more in agriculture as other insecticides are being phased out. Although pyrethroids are neurotoxic for insects, exposure to them is generally considered safe for humans by federal authorities.

The study is the first making the connection between pyrethroid exposure and genetic risk for Parkinson’s, and thus needs follow-up investigation, says co-senior author Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine.

The genetic variation the team probed, which has been previously tied to Parkinson’s in larger genome-wide association studies, was in a non-coding region of a MHC II (major histocompatibility complex class II) gene, part of a group of genes that regulate the immune system.

“We did not expect to find a specific association with pyrethroids,” Tansey says. “It was known that acute exposure to pyrethroids could lead to immune dysfunction, and that the molecules they act on can be found in immune cells; now we need to know more about how longer-term exposure affects the immune system in a way that increases risk for Parkinson’s.”

“There is already ample evidence that brain inflammation or an overactive immune system can drive the progression of Parkinson’s. What we think may be happening here is that environmental exposures may be altering some people’s immune responses, in a way that promotes chronic inflammation in the brain.”

For this study, Emory investigators led by Tansey and Jeremy Boss, PhD, chair of microbiology and immunology, teamed up with Stewart Factor, DO, head of Emory’s Comprehensive Parkinson’s Disease Center, and public health researchers from UCLA led by Beate Ritz, MD, PhD. The first author of the paper is MD/PhD student George T. Kannarkat.

The UCLA researchers used a California state geographical database covering 30 years of pesticide use in agriculture. They defined exposure based on proximity (someone’s work and home addresses), but did not measure levels of pesticides in the body. Pyrethroids are thought to decay relatively quickly, especially in sunlight, with half-lives in soil of days to weeks. Read more

Posted on April 27, 2015 by Quinn Eastman in Immunology, Neuro Leave a comment