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

Muscle cell boundaries: some assembly required

The worm C elegans gives insight into muscle cell assembly + architecture Read more

gut microbiota

Neurodegeneration accelerated by intestinal bacteria?

An influential theory about the anatomical trajectory of Parkinson’s disease is getting a microbial boost. The idea, first proposed by neuroanatomist Heiko Braak in 2003, is that pathology and neurodegeneration start in the intestines and then travel to the brain. See this article in Scientific American for background.

Illustration showing neurons with Lewy bodies, depicted as small red spheres, which are deposits of aggregated proteins in brain cells

Timothy Sampson, in Emory’s Department of Physiology, was first author on a recent paper in eLife, which explores the idea that prion-like proteins produced by intestinal bacteria can accelerate the aggregation of similar proteins found in our cells. The findings suggest that interventions targeting intestinal bacteria could modulate neurodegeneration.

Sampson, a former Emory graduate student who did postdoctoral work in Sarkis Mazmaniam’s lab at Caltech, says he will continue the project here. He and his colleagues were looking at the interaction between a bacterial protein called Curli – involved in adhesion + biofilms — and the aggregation-prone mammalian protein alpha-synuclein, known as a main component of the Lewy body clumps seen in Parkinson’s. The experiments were in a mouse model of Parkinson’s neurodegeneration, in which human alpha-synuclein is overproduced.

Looking ahead, Sampson says he is interested in what signals from the microbiome may trigger, accelerate or slow synuclein aggregation. He’s also looking at where in the GI tract synuclein begins to aggregate, possibly facilitated by particular cells in the intestine, and whether the observations with alpha-synuclein hold true for other proteins such as amyloid-beta in Alzheimer’s.

Posted on by Quinn Eastman in Neuro Leave a comment

Microbiome critical for bone hormone action

Intestinal microbes are necessary for the actions of an important hormone regulating bone density, according to two papers from the Emory Microbiome Research Center. The papers represent a collaboration between Roberto Pacifici, MD and colleagues in the Department of Medicine and laboratory of Rheinallt Jones, PhD in the Department of Pediatrics.

Together, the results show how probiotics or nutritional supplementation could be used to modulate immune cell activity related to bone health. The two papers, published in Nature Communications and Journal of Clinical Investigation, are the first reports of a role for intestinal microbes in the mechanism of action of PTH (parathyroid hormone), Pacifici says.

PTH increases calcium levels in the blood and can either drive bone loss or bone formation, depending on how it is produced or administered. Continuous excessive production of PTH, or primary hyperparathyroidism, is a common endocrine cause of osteoporosis. Yet in another context, intermittent external PTH stimulates bone formation, and is an FDA-approved treatment for osteoporosis – also used off-label for fracture repair in athletes. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Are immune-experienced mice better for sepsis research?

Why isn’t a laboratory mouse more like a human? There are several answers, beyond the differences in size and physiology between mice and humans, such as microbiome and immunological experience. Emory researchers led by Mandy Ford and Craig Coopersmith recently published a couple papers that aim to take those factors into account.

The goal is to make mouse immune systems and microbiomes more complex and more like those in humans, so the mice they can better model the deadly derangement of sepsis. So far, sepsis research in mice has been a poor predictor of clinical success. This aligns with work at the National Institutes of Health on “wildling” mice, which have microbes more like wild mice. (Lab Land likes noticing a trend that Emory researchers are part of.)

One Emory paper, in FASEB Journal, shows that mortality in a mouse model of sepsis varies according to the commercial facility where the mice came from. When the mice were allowed to live together and exchange microbes, mortality numbers evened out.

Another, published in JCI Insight, looks at mice that have more memory T cells than naïve mice, since adult humans have a high proportion of memory T cells in their immune systems. Other scientists have shown that sepsis leads to a wipeout of memory T cells, and probably vulnerability in defending against infection. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Emory Microbiome Research Center inaugural symposium

Interest in bacteria and other creatures living on and inside us keeps climbing. On August 15 and 16, scientists from a wide array of disciplines will gather for the Emory Microbiome Research Center inaugural symposium.

On the first day, Lab Land is looking forward to hearing from several of the speakers, touching on topics stretching from insects/agricultural pathogens to neurodegenerative disease. The second day is a hands on workshop organized by instructor Anna Knight on sorting through microbiome data. The symposium will be at WHSCAB (Woodruff Health Sciences Center Auditorium). Registration before August 2 is encouraged!

Many of the projects that we highlighted four years ago, when Emory held its first microbiome symposium, have continued and gathered momentum. Guest keynotes are from Rodney Newberry from WUSTL and Gary Wu from Penn.

 

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

Everything in moderation, especially TH17 cells

I was struck by one part of Mirko Paiardini’s paper that was published this week in Journal of Clinical Investigation. It describes a treatment aimed at repairing immune function in SIV-infected monkeys, with an eye toward helping people with HIV one day. One of the goals of their IL-21 treatment is to restore intestinal Th17 cells, which are depleted by viral infection. In this context, IL-21’s effect is anti-inflammatory.

However, Th17 cells are also involved in autoimmune disease. A recent Cell Metabolism paper from endocrinologist Roberto Pacifici and colleagues examines Th17 cells, with the goal of treating bone loss coming from an overactive parathyroid. In that situation, too many Th17 cells are bad and they need to be beaten back. Fortunately, both an inexpensive blood pressure medication and a drug under development for psoriasis seem to do just that.

Note for microbiome fans: connections between Th17 cells and intestinal microbes (segmented filamentous bacteria) are strengthening. It gets complicated because gut microbiota, together with Th17 cells, may influence metabolic disease and Th17-like cells are also in the skin — location matters.

Posted on by Quinn Eastman in Immunology Leave a comment