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

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

nuclear receptor

Biochemists grab slippery target: LRH-1

To fight fat, scientists had to figure out how to pin down a greasy, slippery target. Researchers at Emory University and Baylor College of Medicine have identified compounds that potently activate LRH-1, a liver protein that regulates the metabolism of fat and sugar. These compounds have potential for treating diabetes, fatty liver disease and inflammatory bowel disease.

Their findings were recently published online in Journal of Medicinal Chemistry.

LRH-1 is thought to sense metabolic state by binding a still-undetermined group of greasy molecules: lipids or phospholipids. It is a nuclear receptor, a type of protein that turns on genes in response to hormones or vitamins. The challenge scientists faced was in designing drugs that fit into the same slot occupied by the lipids.

“Phospholipids are typically big, greasy molecules that are hard to deliver as drugs, since they are quickly taken apart by the digestive system,” says Eric Ortlund, PhD, associate professor of biochemistry at Emory University School of Medicine. “We designed some substitutes that don’t fall apart, and they’re highly effective – 100 times more potent that what’s been found already.”

Previous attempts to design drugs that target LRH-1 ran into trouble because of the grease. Two very similar molecules might bind LRH-1 in opposite orientations. Ortlund’s lab worked with Emory chemist Nathan Jui, PhD and his colleagues to synthesize a large number of compounds, designing a “hook” that kept them in place. Based on previous structural studies, the hook could stop potential drugs from rotating around unpredictably. Read more

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Unlocking a liver receptor puzzle

Imagine a key that opens a pin tumbler lock.  A very similar key can also fit into the lock, but upside down in comparison to the first key.

Biochemist Eric Ortlund and colleagues have obtained analogous results in their study of how potential diabetes drugs interact with their target, the protein LRH-1. Their research, published in Journal of Biological Chemistry, shows that making small changes to LRH-1-targeted compounds makes a huge difference in how they fit into the protein’s binding pocket.

First author Suzanne Mays, a graduate student in Emory's MSP program

First author Suzanne Mays, a graduate student in Emory’s MSP program

This research was selected as “Paper of the Week” by JBC and is featured on the cover of the December 2 issue.

LRH-1 (liver receptor homolog-1) is a nuclear receptor, a type of protein that turns on genes in response to small molecules like hormones or vitamins.  LRH-1 acts in the liver to regulate metabolism of fat and sugar.

Previous research has shown that activating LRH-1 decreases liver fat and improves insulin sensitivity in mice. Because of this, many research teams have been trying to design synthetic compounds that activate this protein, which could have potential to treat diabetes and nonalcoholic fatty liver disease. This has been a difficult task, because not much is known about how synthetic compounds interact with LRH-1 and switch it into the active state. Read more

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