Multiple myeloma patients display weakened antibody responses to mRNA COVID vaccines

Weakened antibody responses to COVID-19 mRNA vaccines among most patients with multiple Read more

Precision medicine with multiple myeloma

“Precision medicine” is an anti-cancer treatment strategy in which doctors use genetic or other tests to identify vulnerabilities in an individual’s cancer subtype. Winship Cancer Institute researchers have been figuring out how to apply this strategy to multiple myeloma, with respect to one promising drug called venetoclax, in a way that can benefit the most patients. Known commercially as Venclexta, venetoclax is already FDA-approved for some forms of leukemia and lymphoma. Researchers had observed that multiple Read more

Promiscuous protein droplets regulate immune gene activity

Biochemists at Emory are achieving insights into how an important regulator of the immune system switches its function, based on its orientation and local environment. New research demonstrates that the glucocorticoid receptor (or GR) forms droplets or “condensates” that change form, depending on its available partners. The inside of a cell is like a crowded nightclub or party, with enzymes and other proteins searching out prospective partners. The GR is particularly well-connected and promiscuous, and Read more

transcription factors

Promiscuous protein droplets regulate immune gene activity

Biochemists at Emory are achieving insights into how an important regulator of the immune system switches its function, based on its orientation and local environment. New research demonstrates that the glucocorticoid receptor (or GR) forms droplets or “condensates” that change form, depending on its available partners.

The inside of a cell is like a crowded nightclub or party, with enzymes and other proteins searching out prospective partners. The GR is particularly well-connected and promiscuous, and has the potential to interact with many other proteins. It is a type of protein known as a transcription factor, which turns some genes on and others off, depending on how it is binding DNA.

These are fluorescent droplets of the glucocorticoid receptor (GR) in red, with a coregulator protein in green. When DNA is added, the co-regulator forms its own droplets on the surface of GR droplets. Image courtesy of Filipp Frank

“It is now thought that most transcription factors form or are recruited into condensates, and that condensation modulates their function,” says Filipp Frank, PhD, first author of the paper and a postdoctoral instructor in Eric Ortlund’s lab in the Department of Biochemistry. “What’s new is that we identified a DNA-dependent change in GR condensates, which has not been described for other transcription factors.”

The results are published in Proceedings of the National Academy of Sciences. Ortlund is a co-author of the paper, along with postdoctoral fellow Xu Liu, PhD.

Understanding how the GR works could help researchers find anti-inflammatory drugs with reduced side effects. The GR is the target for corticosteroid drugs such as dexamethasone, which is currently used to treat COVID-19 as well as allergies, asthma and autoimmune diseases.

Corticosteroids’ harmful side effects are thought to come from turning on genes involved in metabolism and bone growth, while their desired anti-inflammatory effects result from turning other inflammatory and immune system genes off. Researchers want to find alternatives that could separate those two functions.

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