‘Genetic doppelgangers:’ Emory research provides insight into two neurological puzzles

An international team led by Emory scientists has gained insight into the pathological mechanisms behind two devastating neurodegenerative diseases. The scientists compared the most common inherited form of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) with a rarer disease called spinocerebellar ataxia type 36 (SCA 36). Both of the diseases are caused by abnormally expanded and strikingly similar DNA repeats. However, ALS progresses quickly, typically killing patients within a year or two, while the disease Read more

Emory launches study on COVID-19 immune responses

Emory University researchers are taking part in a multi-site study across the United States to track the immune responses of people hospitalized with COVID-19 that will help inform how the disease progresses and potentially identify new ways to treat it.  The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The study – called Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) – launched Friday. Read more

Marcus Lab researchers make key cancer discovery

A new discovery by Emory researchers in certain lung cancer patients could help improve patient outcomes before the cancer metastasizes. The researchers in the renowned Marcus Laboratory identified that highly invasive leader cells have a specific cluster of mutations that are also found in non-small cell lung cancer patients. Leader cells play a dominant role in tumor progression, and the researchers discovered that patients with the mutations experienced poorer survival rates. The findings mark the first Read more

Molecular and Systems Pharmacology

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

Posted on by Quinn Eastman in Uncategorized Leave a comment

Ancient protein flexibility may drive ‘new’ functions

A mechanism by which stress hormones inhibit the immune system, which appeared to be relatively new in evolution, may actually be hundreds of millions of years old.

A protein called the glucocorticoid receptor or GR, which responds to the stress hormone cortisol, can take on two different forms to bind DNA: one for activating gene activity, and one for repressing it. In a paper published Dec. 28 in PNAS, scientists show how evolutionary fine-tuning has obscured the origin of GR’s ability to adopt different shapes.

“What this highlights is how proteins that end up evolving new functions had those capacities, because of their flexibility, at the beginning of their evolutionary history,” says lead author Eric Ortlund, PhD, associate professor of biochemistry at Emory University School of Medicine.

GR is part of a family of steroid receptor proteins that control cells’ responses to hormones such as estrogen, testosterone and aldosterone. Our genomes contain separate genes encoding each one. Scientists think that this family evolved by gene duplication, branch by branch, from a single ancestor present in primitive vertebrates. Read more

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