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

rapamycin

Connections between starvation and immunological memory

Researchers at Emory have been revealing several connections between cells’ responses to starvation and immunological memory. The latest example of this is a paper in Nature Immunology from Rafi Ahmed’s lab, showing that the cellular process of autophagy (literally: self-consumption) is essential for forming and maintaining memory T cells.

This finding has some practical implications for vaccination and could point the way to additives that could boost vaccine effectiveness in elderly humans. Researchers at Oxford have demonstrated that autophagy is diminished in T cells from aged mice, and T cell responses could be boosted in older mice using the autophagy-inducing compound spermidine. Read more

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Unexpected effect on flu immunity

Immunologists reported recently that the drug rapamycin, normally used to restrain the immune system after organ transplant, has the unexpected ability to broaden the activity of a flu vaccine.

The results, published in Nature Immunology, indicate that rapamycin steers immune cells away from producing antibodies that strongly target a particular flu strain, in favor of those that block a wide variety of strains. The results could help in the effort to develop a universal flu vaccine.

This study was inspired by a 2009 Nature study from Koichi Araki and Emory Vaccine Center director Rafi Ahmed, reports Jon Cohen in Science magazine. Read more

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mTOR inhibitors gaining favor for breast cancer treatment

This week, breast cancer researchers have been reporting encouraging clinical trial results with the drug everolimus at the San Antonio Breast Cancer Symposium. Everolimus is a mTOR inhibitor, first approved by the FDA for treatment of kidney cancer and then for post-transplant control of the immune system.

Ruth O’Regan, MD, director of the Translational Breast Cancer Research Program at Winship Cancer Institute, has led clinical studies of everolimus in breast cancer and has championed the strategy of combining mTOR inhibitors with current treatments for breast cancer.

She recently explained the rationale to the NCI Cancer Bulletin:

She views the combination therapy as a potential alternative to chemotherapy for treating ER-positive advanced breast cancer when hormonal therapies have stopped working.

When resistance to hormonal therapies occurs, Dr. O’Regan explained, additional signaling pathways become activated. Unlike chemotherapy, which targets rapidly dividing cells, mTOR inhibitors are an example of the kind of treatment that may block growth-promoting signaling pathways.

Currently, Winship researchers are examining a combination involving everolimus and the EGFR inhibitor lapatinib for “triple-negative” breast cancer, a particularly aggressive and difficult-to-treat variety.

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Many roads to memory T cells

When our bodies encounter a bacteria or a virus, the immune system sends some cells out to fight the invader and keeps others in reserve, in order to respond faster and stronger the next time around. Vaccination depends on this phenomenon, called immunological memory.

Several recent papers — from Emory and elsewhere – provide insight into this process, and highlight this area of research as especially active lately.

Researchers led by Rafi Ahmed and Chris Larsen at Emory found that rapamycin, a drug usually given to transplant patients to block rejection, actually stimulates the formation of memory T cells. Rapamycin appears to nudge immune cells when they have to make a decision whether to hunker down to become a memory cell.

The immunosuppressant drug rapamycin was discovered in soil from Easter Island

The immunosuppressant drug rapamycin was discovered in soil from Easter Island

Similarly, the anti-diabetes drug metformin, which affects fatty acid metabolism, can also stimulate the formation of memory T cells, according to research that was published in the same issue of Nature.

In addition, Wnt signaling, which plays critical roles in embryonic development and cancer, influences memory T cell formation as well, according to a July paper in Nature Medicine.

To summarize — pushing on several different “buttons” produces the same thing: more memory T cells. How are the wires behind the buttons connected? Work by Ahmed and others may eventually help enhance vaccine efficacy or fight cancer with the immune system.

Rapamycin, the focus of the Ahmed/Larsen paper, was also recently found to slow aging in mice. However, with previous anti-aging research findings, translating results into the human realm has been a considerable challenge.

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