Education is a life preserver, after heart attack

Only about 13 percent of the people coming through Emory's cath labs are actually having a heart attack.

Six beautiful images -- choose your favorites

Emory's Office of Postdoctoral Education is holding a Best Image contest. The deadline to vote is this Thursday, April 30. You can look at these beautiful images (and guess exactly what they are, based on what lab they come from), but to VOTE, you need to go to the OPE site. This is part of the run up to their Postdoctoral Research Symposium at the end of May. (Hat tip to Ashley Freeman in Dept of Medicine!)    

Congratulations to AAAS Mass Media fellows

Anzar Abbas --> HHMI, Katie Strong --> SacBee

Low doses of imatinib can stimulate innate immunity

Low doses of the anti-cancer drug imatinib can spur the bone marrow to produce more innate immune cells to fight against bacterial infections, Emory and Winship Cancer Institute researchers have found.

The results were published this week in the journal PLOS Pathogens.

The findings suggest imatinib, known commercially as Gleevec, or related drugs could help doctors treat a wide variety of infections, including those that are resistant to antibiotics, or in patients who have weakened immune systems. The research was performed in mice and on human bone marrow cells in vitro, but provides information on how to dose imatinib for new clinical applications.

“We think that low doses of imatinib are mimicking ‘emergency hematopoiesis,’ a normal early response to infection,” says senior author Daniel Kalman, PhD, associate professor of pathology and laboratory medicine at Emory University School of Medicine.

Imatinib, is an example of a “targeted therapy” against certain types of cancer. It blocks tyrosine kinase enzymes, which are dysregulated in cancers such as chronic myelogenous leukemia and gastrointestinal stromal tumors.

Imatinib also inhibits normal forms of these enzymes that are found in healthy cells. Several pathogens – both bacteria and viruses – exploit these enzymes as they transit into, through, or out of human cells. Researchers have previously found that imatinib or related drugs can inhibit infection of cells by pathogens that are very different from each other, including tuberculosis bacteria and Ebola virus. Read more

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

Recording seizures from within the brain

To go along with the (new) Spring 2015 Emory Medicine magazine set of features on deep brain stimulation for depression, movement disorders and epilepsy, here is a fascinating 2013 case report from Emory neurosurgeon Robert Gross and colleagues. The first author is electrical engineer Otis Smart.

It’s an example of the kinds of insights that can be obtained from implantable electrical stimulation devices, which can record signals from seizures inside the brain over long periods of time (more than a year).

As the authors write, “the technology can record brain activity while the patient is in a more naturalistic environment than a hospital, becoming an invasive ambulatory EEG.” Read more

Posted on by Quinn Eastman in Neuro 1 Comment

Regrouping on fragile X drug strategies

Fragile X syndrome has many fascinating aspects:

* the complex inheritance pattern

* its status as the most common inherited form of intellectual disability and a major single-gene cause of autism spectrum disorder (ASD)

*the importance of the RNA-binding protein FMRP as a regulator of synaptic plasticity in neurons

*the potential applicability of drugs developed for fragile X for other forms of ASD

Readers interested in neurodevelopment disorders may want to check out this Nature Reviews Drug Discovery piece, which chews over some setbacks in clinical research on fragile X. Emory researchers have a strong connection with the drug strategies used in the recent clinical trials, but have also been working on alternative approaches. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Potential HIV drugs hit three targets at once

Drug discovery veteran Dennis Liotta and his team continue to look for ways to fight against HIV. Working with pharmaceutical industry colleagues, he and graduate student Anthony Prosser have discovered compounds that are active against three different targets: immune cells’ entry gates for the virus (CCR5 and CXCR4), and the replication enzyme reverse transcriptase. That’s like one arrow hitting three bulls eyes. An advantage for these compounds: it could be less likely for viral resistance to develop.

For more, please go to the American Chemical Society — there will be a press conference from the ACS meeting in Denver on Monday, and live YouTube.

Posted on by Quinn Eastman in Immunology Leave a comment

ACC 2015: Newer heart risk calculator may better accounts for racial differences

A risk calculator for cardiovascular disease, developed as a companion for the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, may account for racial differences in sub-clinical vascular function better than the Framingham Risk Score, Emory cardiology researchers say.

Their findings are scheduled for presentation Monday at the American College of Cardiology meeting in San Diego.

African Americans, especially men, tend to have a higher prevalence of cardiovascular disease, but this differences are not reflected in the Framingham Risk score. Arterial stiffness is a sign of heart disease risk that tends to appear more prominently among African Americans than whites. Cardiovascular research fellow Jia Shen, MD, MPH, and Emory colleagues analyzed data on arterial stiffness and structure from 1235 people – 777 whites and 458 African-Americans — enrolled in two large studies (Center for Health Discovery and Well Being and META-Health). Read more

Posted on by Quinn Eastman in Heart Leave a comment

Who regulates the regulators? Drosha

MicroRNAs have emerged as important master regulators in cells, since each one can shut down several target genes. Riding on top of the master regulators is Drosha, the RNA-cutting enzyme that initiates microRNA processing in the nucleus. Drosha and its relative Dicer have been attracting attention in cancer biology, because they are thought to be behind a phenomenon where cancerous cells can “infect” their healthy neighbors via tiny membrane-clothed packets called exosomes.

At Emory, pharmacologist Zixu Mao and colleagues recently published in Molecular Cell their findings that Drosha is regulated by stress (experimentally: heat or peroxide) through p38 MAP kinase.

Although we mention relevance to cancer above, this is one of those basic cell biology findings that may have applicability to several areas of medicine. Alterations in miRNA processing have been linked to neurodegenerative disease (Fragile X-associated tremor/ataxia syndrome, for one example). MicroRNA-packed exosomes are also being studied by biomedical engineers as potential therapeutic tools in regenerative medicine, so knowing what cellular stress does to miRNA production could be useful. Read more

Posted on by Quinn Eastman in Cancer, Heart, Neuro Leave a comment

Are TrkB agonists ready for translation into the clinic?

Our recent news item on Emory pathologist Keqiang Ye’s obesity-related research (Molecule from trees helps female mice only resist weight gain) understates how many disease models the proto-drug he and his colleagues have discovered, 7,8-dihydroxyflavone, can be beneficial in. We do mention that Ye’s partners in Australia and Shanghai are applying to begin phase I clinical trials with a close relative of 7,8-dihydroxyflavone in neurodegenerative diseases.

Ye’s 2010 PNAS paper covered models of Parkinson’s, stroke and seizure. Later publications take on animal models of depression, Alzheimer’s, fear learning, hearing loss and peripheral nerve injury. Although those findings begin to sound too good to be true, outside laboratories have been confirming the results (not 100 percent positive, but nothing’s perfect).  Plenty of drugs don’t make it from animal models into the clinic, but this is a solid body of work so far.

 

 

 

Posted on by Quinn Eastman in Neuro Leave a comment

Next generation sequencing roundup

The increasing clinical use of next generation sequencing, especially whole exome and whole genome, continues to be a hot topic. The ability to contribute to diagnosis, clinical utility, incidental findings and whether insurance will cover next-gen sequencing are all changing.

A Nature Medicine article lays out a lot of the emerging business issues on next-gen sequencing. On the topic of incidental findings, Buzzfeed science editor Virginia Hughes last week reported stories of women who receive a cancer diagnosis as a result of having a prenatal genetic test.

“These cases, though extremely rare, are raising ethical questions about the unregulated – and rapidly evolving – genetic-testing industry,” Buzzfeed says.

At a recent Department of Pediatrics seminar, Emory geneticist Michael Gambello described examples of how whole exome sequencing, performed to diagnose intellectual disability or developmental problems in a child, can uncover cancer or neurodegenerative disease risk mutations in a parent. The question becomes, whether to notify the parent for something that may or may not be actionable. This is why Emory Genetics Laboratory’s whole exome sequencing service has an extensive “opt-in/opt-out” consent process.

Emory Genetics Laboratory executive director Madhuri Hegde, working with the Association of Molecular Pathology, has been a leader in pushing genetic testing laboratories to adopt best practices. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

BAI1: a very multifunctional protein

Everything is connected, especially in the brain. A protein called BAI1 involved in limiting the growth of brain tumors is also critical for spatial learning and memory, researchers have discovered.

Mice missing BAI1 have trouble learning and remembering where they have been. Because of the loss of BAI1, their neurons have changes in how they respond to electrical stimulation, and subtle alterations in parts of the cell needed for information processing.

The findings may have implications for developing treatments for neurological diseases, because BAI1 is part of a protein regulatory network neuroscientists think is connected with autism spectrum disorders.

The results were published online March 9 in Journal of Clinical Investigation.

Erwin Van Meir, PhD, and his colleagues at Winship Cancer Institute of Emory University have been studying BAI1 (brain-specific angiogenesis inhibitor 1) for several years. Part of the BAI1 protein can stop the growth of new blood vessels, which growing cancers need. Normally highly active in the brain, the BAI1 gene is lost or silenced in brain tumors, suggesting that it acts as a tumor suppressor.

The researchers were surprised to find that the brains of mice lacking the BAI1 gene looked normal anatomically. They didn’t develop tumors any faster than normal, and they didn’t have any alterations in their blood vessels, which the researchers had anticipated based on BAI1’s role in regulating blood vessel growth. What they did have was problems with spatial memory.

Read more

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

Reviving drugs with anti-stroke potential, minus side effects

Neuroprotective drugs might seem impractical or improbable right now, after two big clinical trials testing progesterone in traumatic brain injury didn’t work out. But one close observer of drug discovery is predicting a “coming boom in brain medicines.” Maybe this research, which Emory scientists have been pursuing for a long time, will be part of it.

In the 1990s, neuroscientists identified a class of drugs that showed promise in the area of stroke. NMDA receptor antagonists could limit damage to the brain in animal models of stroke. But one problem complicated testing the drugs in a clinical setting: the side effects included disorientation and hallucinations.

Now researchers have found a potential path around this obstacle. The results were published in Neuron.

“We have found neuroprotective compounds that can limit damage to the brain during ischemia associated with stroke and other brain injuries, but have minimal side effects,” says senior author Stephen Traynelis, PhD, professor of pharmacology at Emory University School of Medicine.

“These compounds are most active when the pH is lowered by biochemical processes associated with injury of the surrounding tissue. This is a proof of concept study that shows this mechanism of action could potentially be exploited clinically in several conditions, such as stroke, traumatic brain injury and subarachnoid hemorrhage.” Read more

Posted on by Quinn Eastman in Neuro Leave a comment
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