I3 Venture awards info

Emory is full of fledgling biomedical proto-companies. Some of them are actual corporations with employees, while others are ideas that need a push to get them to that point. Along with the companies highlighted by the Emory Biotech Consulting Club, Dean Sukhatme’s recent announcement of five I3 Venture research awards gives more examples of early stage research projects with commercial potential. This is the third round of the I3 awards; the first two were Wow! Read more

Take heart, Goldilocks -- and get more sleep

Sleeping too little or too much increases the risk of cardiovascular events and death in those with coronary artery disease, according to a new paper from Emory Clinical Cardiovascular Research Institute. Others have observed a similar U-shaped risk curve in the general population, with respect to sleep duration. The new study, published in American Journal of Cardiology, extends the finding to people who were being evaluated for coronary artery disease. Arshed Quyyumi, MD and colleagues analyzed Read more

Repurposing a transplant drug for bone growth

The transplant immunosuppressant drug FK506, also known as tacrolimus or Prograf, can stimulate bone formation in both cell culture and animal Read more

Frank Anania

Leaky gut plus diet together drive liver disease

 

Frank Anania, MD

Lots of people in the United States consume a diet that is high in sugar and fat, and many develop non-alcoholic fatty liver disease, a relatively innocuous condition. NASH (non-alcoholic steatohepatitis) is the more unruly version, linked to elevated risk of cardiovascular and metabolic diseases, and can progress to cirrhosis. NASH is expected to become the leading indication for liver transplant. But only a fraction of people with non-alcoholic fatty liver disease go on to develop NASH.

Thus, many researchers are trying to solve this equation:

High-sugar, high-fat diet plus X results in NASH.

Emory hepatologist Frank Anania and colleagues make the case in a recent Gastroenterology paper that a “leaky gut”, allowing intestinal microbes to promote liver inflammation, could be a missing X factor.

Anania’s lab started off with mice fed a diet high in saturated fat, fructose and cholesterol (in the figure, PrintHFCD). This combination gives the mice moderate fatty liver disease and metabolic syndrome (see this 2015 paper, and we can expect to hear more about this model soon from Saul Karpen). Leaky gut, brought about by removing a junction protein from intestinal cells, sped up and intensified the development of NASH.

The authors say that this model could be useful for the study of NASH, which has been difficult to reproduce in mice.

The researchers could attenuate liver disease in the mice by treatment with antibiotics or sevelamer, a phosphate binding polymer that soaks up inflammatory toxins from bacteria. Sevelamer is now used to treat excess phosphate in patients with chronic kidney disease, and is being studied clinically in connection with insulin resistance.
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Reversing liver fibrosis via adiponectin

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver conditions in the United States, affecting 30 percent of the population, and increasing — and likely to catch up in prevalence with obesity and diabetes. In NAFLD, fat content of the liver is elevated to 6 percent or more in people who drink in moderation or not at all. Patients will first present with elevated liver enzyme values in blood tests, but then an imaging test or tissue biopsy may be ordered to evaluate the extent of the damage. NAFLD is mostly asymptomatic and is variable in severity; a majority of those afflicted do not need drug treatments. However, NAFLD is thought to be a preliminary condition that can eventually progress to severe manifestations, such as cirrhosis, hepatocellular carcinoma, and end stage liver failure.

Progression of liver disease, from NIDDK.  This article is a guest post from Kristina Bargeron Clark, a graduate student at Emory and communications chair for Women in Bio-Atlanta. Her website is www.inkcetera.org.

Progression of liver disease, from NIDDK.
This is a guest post from Kristina Bargeron Clark, a MMG graduate student at Emory and communications chair for Women in Bio-Atlanta. Her website is www.inkcetera.org.

At Emory, Frank Anania, director of the Department of Medicine’s Division of Digestive Diseases, and his colleagues are developing a tool to treat liver disease. A recent publication in the FASEB Journal describes their investigation into the potential for the hormone adiponectin to modulate liver fibrosis.

Adiponectin is produced by adipose tissue, but is known to decrease in overweight people with metabolic disease. Research by others indicates that it may prevent heart and kidney fibrosis. The Emory team’s studies were conducted to determine if adiponectin could also reduce liver fibrosis.

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Spotlight on liver fibrosis

For a May explainer, we’d like to spotlight liver fibrosis. Two recent papers from Emory research teams in the journal Hepatology focus on this process.

Liver fibrosis is an accumulation of scar tissue and proteins outside cells that occurs as a result of chronic damage to the liver. It involves inflammation and immune cells, as well as activation of a type of cell in the liver (hepatic stellate cells), which usually stores fat and vitamin A. Fibrosis and cirrhosis are not the same. Think of it this way: cirrhosis is the late stage of the disease, but fibrosis is how someone can get there.

The liver has a remarkable, even mythical, ability to regenerate, but there is a long list of ways that someone can injure this most vital organ. Quickly – take too much acetaminophen (the most common cause of acute liver failure in the United States). More slowly – develop a hepatitis C infection. Drink large quantities of alcohol. Or something with more subtle effects: consume a diet high in sugar, which can lead to fatty liver. The relationship between fatty liver and more serious liver disease is currently under investigation.

One of the Hepatology papers comes at liver fibrosis from a malaria angle. Patrice Mimche, Tracey Lamb and colleagues show the involvement of EphB2 tyrosine kinase, a signaling molecule not previously known to be involved in liver fibrosis.

Malaria parasites have a complex life cycle, growing in the liver and then in the blood. Lamb says an important part of her paper was the finding that in mouse malaria infection, EphB2 is activated during the blood stage on immune cells infiltrating into the liver. EphB2 (an active drug discovery target) may be acting as a tissue-specific adhesion molecule, she says.

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Posted on by Quinn Eastman in Immunology Leave a comment