Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

Make ‘em fight: redirecting neutrophils in CF

Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus. Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more

Rheinallt Jones

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

Providing the potent part of probiotics

A Emory News item on a helpful part of the microbiome focuses on how the same type of bacteria – lactobacilli – activates the same ancient signaling pathway in intestinal cells in both insects and mammals. It continues a line of research from Rheinallt Jones and Andrew Neish on how beneficial bacteria stimulate wound healing by activating ROS (reactive oxygen species).

Asma Nusrat, MD

A idea behind this research is: if we know what parts of the bacteria stimulate healing, perhaps doctors can deliver that material, or something very close, to patients directly to treat intestinal diseases such as Crohn’s or ulcerative colitis.

This idea has advanced experimentally, as demonstrated by two papers from Jones and Neish’s frequent collaborator, Asma Nusrat, who recently moved from Emory to the University of Michigan. This team had shown that a protein produced by human intestinal cells called annexin A1 activates ROS, acting through the same N-formyl peptide receptors that bacteria do.

Nusrat told me Friday her team began investigating annexins a decade ago at Emory, and it was fortuitous that Neish was working on beneficial bacteria right down the hall, since it is now apparent that annexin A1 and the bacteria are activating the same molecular signals. (Did you know there is an entire conference devoted to annexins? I didn’t until a few days ago.)

In a second Journal of Clinical Investigation paper published this February, Nusrat and her colleagues show that intestinal cells release vesicles containing annexin A1 following injury. The wound closure-promoting effects of these vesicles can be mimicked with nanoparticles containing annexin A1. The nanoparticles incorporate a form of collagen, which targets them to injured intestinal tissue. Read more

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