Quinn Eastman

Elevated (but still low) troponin as a long term cardio biomarker

This weekend (March 10) at the American College of Cardiology meeting, data will emerge on whether expensive and much-discussed PCSK9 inhibitors can lower the risk of heart disease as much as they reduce LDL cholesterol.

To help doctors decide who should take cholesterol-lowering drugs that cost thousands of dollars a year, the focus of discussion could fall on risk models, such as the Framingham score and its successors, or other biomarkers besides various forms of cholesterol. What a coincidence! We have experts on those topics at Emory Clinical Cardiovascular Research Institute: ECCRI co-director Arshed Quyyumi, MD and Laurence Sperling, MD, Director of Preventive Cardiology at the Emory Clinic.

Cardiologists led by Quyyumi have a recent paper in Journal of the American Heart Association looking at troponin as a long-term cardiovascular disease biomarker. Troponin is familiar to cardiologists because it is a sign of acute damage to the heart muscle. If someone with chest pain goes to the emergency department of a hospital, a test for troponin in the blood can say whether a heart attack occurred.

However, as clinical tests for troponin have become more sensitive in the last decade, interpretation has moved past just a “yes/no” question. The levels of troponin now detectable are much smaller than those used to confirm a heart attack. Elevated troponin can be detected in all sorts of situations where the heart is under stress, including after strenuous exercise in healthy individuals. The “optimal cutoff” the Emory authors use in some of their statistical analyses is 5.2 picograms per milliliter. This graph, derived from a 2011 Circulation paper, illustrates just how low that is. Read more

Posted on by Quinn Eastman in Heart Leave a comment

When circulating ambulances disappear

Someone driving around a city on a regular basis will see ambulances. At times they’re going somewhere fast; sometimes they’re just driving. What if, on a given day, fewer ambulances are visible?

One possible conclusion might be: the ambulances are away responding to a group of people who need help. This effect resembles what Arshed Quyyumi and colleagues from Emory Clinical Cardiovascular Research Institute observed in a recent paper, published in the Journal of the American Heart Association.

Arshed Quyyumi, MD

Quyyumi’s team looked at progenitor cells, which circulate in the blood and are attracted to sites of injury.  In a group of 356 patients with stable coronary artery disease, the researchers saw that some (31 percent) had “ExMI” – exercise-mediated myocardial ischemia. That means impairments in blood flow were visible via cardiac imaging under the stress of exercise. This is a relatively mild impairment; participants did not report chest pain. This paper emerges from the MIPS (Mental Stress Ischemia Prognosis) study, 2011-2014.

The ambulance-progenitor cell analogy isn’t perfect; exercise, generally a good thing, increases progenitor cell levels in the blood, says co-first author and cardiology fellow Muhammad Hammadah. The study supports the idea that patients with coronary artery disease may benefit from cardiac rehab programs, which drive the progenitor cells into the ischemic tissue, so they can contribute into vascular repair and regeneration. Read more

Posted on by Quinn Eastman in Heart Leave a comment

FMT microbial transplant for C diff gaining acceptance

In February, the Infectious Diseases Society of America issued new guidelines for fighting Clostridium difficile, the hardy bacterium that can cause life-threatening diarrhea and whose dominance is sometimes a consequence of antibiotic treatment. The guidelines recommend for the first time that FMT (fecal microbiota transplant) be considered for individuals who have repeatedly failed standard antibiotics.

In a nice coincidence, Emory FMT specialists Colleen Kraft and Tanvi Dhere recently published a look at their clinical outcomes with C diff going back to 2012, in Clinical Infectious Diseases. They report 95 percent of patients (122/128) indicated they would undergo FMT again and 70 percent of the 122 said they would prefer FMT to antibiotics as initial treatment if they were to have a recurrence. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Give a zap to Emory brain research for #STATMadness

Next week, we will be asking the Emory research community to support Emory’s entry in a contest. It’s like “Battle of the Bands.” Whoever gets the loudest cheers wins. We have some intriguing neuroscience research. Please help!

STAT Madness is a “March Madness” style bracket competition, but with biomedical research advances as competitors. Universities or research institutes nominate their champions, research that was published the previous year.

Our entry for 2018:

Direct amygdala stimulation can enhance human memory

The findings, from Cory Inman, Jon Willie and colleagues from the Department of Neurosurgery and Joe Manns from Psychology, were the first published example of electrical brain stimulation in humans giving an event-specific boost to memory lasting overnight. The research was conducted with epilepsy patients undergoing an invasive procedure for seizure diagnosis. However, the technology could one day be incorporated into a device aimed at helping those with memory impairments, such as people with traumatic brain injury or neurodegenerative diseases.

Extra note: you may have seen similar neuroscience research in a recent Nature Communications paper, which was described in the New York Times. Cory Inman had some comments below — he and neurosurgeon Robert Gross were co-authors:

The localization to the left lateral temporal cortex was interesting, because it hadn’t been identified as a region that modulates episodic or hippocampus-dependent memory. [The Emory authors stimulated the amygdala.] The more recent paper found a similar size of memory enhancement, with a slightly different and harder memory task of free recall, using “closed-loop” stimulation based on whether the brain is in a ‘bad’ encoding state. It’s possible that closed-loop stimulation could be used with the amygdala as well. 

Emory’s first opponoent is University of California, San Francisco. We are about half way down on the right side of the bracket.

As far as voting, you can fill out a whole bracket or you can just vote for Emory, along with other places you may feel an allegiance to. The contest will go several rounds. The first round begins on February 26. If Emory advances, then people will be able to continue voting for us starting March 2.

At the moment, you can sign up to be reminded to vote with an email address at:
https://signup.statnews.com/stat-madness

Starting Monday, February 26, you can follow the 2018 STAT Madness bracket and vote here:
https://www.statnews.com/feature/stat-madness/bracket/

Please share on social media using the hashtag #statmadness2018.

STAT is a life sciences-focused news site, launched in 2015 by the owner of the Boston Globe. It covers medical research and biotech nationally and internationally. Emory took part in 2017’s contest, with Tab Ansari’s groundbreaking work on SIV remission, a collaboration with Tony Fauci’s lab at NIAID.

 

 

Posted on by Quinn Eastman in Neuro Leave a comment

Nox-ious link to cancer Warburg effect

At Emory, Kathy Griendling’s group is well known for studying NADPH oxidases (also known as Nox), enzymes which generate reactive oxygen species. In 2009, they published a paper on a regulator of Nox enzymes called Poldip2. Griendling’s former postdoc, now assistant professor, Alejandra San Martin has taken up Poldip2.

Griendling first came to Nox enzymes from a cardiology/vascular biology perspective, but they have links to cancer. Nox enzymes are multifarious and it appears that Poldip2 is too. As its full name suggests, Poldip2 (polymerase delta interacting protein 2) was first identified as interacting with DNA replication enzymes.  Poldip2 also appears in mitochondria, indirectly regulating the process of lipoylation — attachment of a fatty acid to proteins anchoring them in membranes. That’s where a recent PNAS paper from San Martin, Griendling and colleagues comes in. It identifies Poldip2 as playing a role in hypoxia and cancer cell metabolic adaptation.

Part of the PNAS paper focuses on Poldip2 in triple-negative breast cancer, more difficult to treat. In TNBC cells, Poldip2’s absence appears to be part of the warped cancer cell metabolism known as the Warburg effect. Lab Land has explored the Warburg effect with Winship’s Jing Chen.

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

Viral vectors ready for delivery

The phrase “viral vector” sounds ominous, like something from a movie about spies and internet intrigue. It refers to a practical delivery system for the gene of your choice. If you are a biomedical researcher and you want to tweak genes in a particular part of the body in an experimental animal, viral vectors are the way to go.

Viral vector-transduced retinal ganglion cell; dendrites and axons labeled with GFP. Courtesy Felix Struebling via Xinping Huang

Emory’s Viral Vector Core was started when eminent neuroscientist Kerry Ressler was at Emory and is now overseen by geneticist Peng Jin. Technical director Xinping Huang and her colleagues can produce high-titer viral vectors, lentivirus and AAV. Discuss with her the best choice. It may depend on the size of the genetic payload you want to deliver and whether you want the gene to integrate into the genome of the target cell.

As gene therapy and CRISPR/Cas9-style gene editing research progresses, we can anticipate demand for services such as those provided by the Viral Vector Core. [Clinical applications are close, but will not be dealt with in the same place!]

Shi-Hua Li’s and Xiao-Jiang Li’s paper on CRISPR/Cas9 gene editing in a mouse model of Huntington’s disease, featured by NBC News last year, credits the Viral Vector Core. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Exotic immune systems are big business

What timing! Just when our feature on Max Cooper and lamprey immunology was scheduled for publication, the Japan Prize Foundation announced it would honor Cooper and his achievements.

Cooper was one of the founders of modern immunology. We connect his early work with his lab’s more recent focus on lampreys, primitive parasites with surprisingly sophisticated immune systems.

Molecules from animals with exotic immune systems can be big business, as Andrew Joseph from STAT News points out. Pharmaceutical giant Sanofi recently bought a company focused on nanobodies, originally derived from camels, llamas and alpacas, for $4.8 billion.

Lampreys’ variable lymphocyte receptors (VLRs) are their version of antibodies, even though they look quite different in molecular terms. Research on VLRs and their origins may seem impractical. However, Cooper’s team has shown their utility as diagnostic tools, and his colleagues have been weaponizing them, possibly for use in cancer immunotherapy.

CAR-T cells have attracted attention for dramatic elimination of certain types of leukemias from the body and also for harsh side effects and staggering costs; see this opinion piece by Georgia Tech’s Aaron Levine. Now many research teams are scheming about how to apply the approach to other types of cancers. The provocative idea is: replace the standard CAR (chimeric antigen receptor) warhead with a lamprey VLR.

Read more

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

Calming an electrical storm in the heart

AT = anterior tubercle of C6, C = carotid artery, LC = longus colli muscle, T = thyroid gland, IJ = internal jugular vein, compressed

The most recent issue of Emory Medicine features a story that first came to Lab Land’s attention when it was presented as an abstract at the 2017 American College of Cardiology Scientific Sessions meeting.

Emory doctors were challenged by a patient who repeatedly developed cardiac arrhythmias, called “refractory electrical storm.” They used a local anesthesia procedure called stellate ganglion block — normally used for complex pain — to calm the storm. Cardiac electrophysiologist Michael Lloyd, who likes solving puzzles, was the one who decided to try it.

Emory anesthesiologist Boris Spektor provided this ultrasound picture of the procedure. Stellate ganglion block is also being tested for conditions such as PTSD. Please read the whole story!

Posted on by Quinn Eastman in Heart Leave a comment

Sifting proteomes for copper nuggets

Just because scientists know the gene responsible for a rare disease doesn’t mean they know what’s going on. NGLY1 is a good example. A handful of children around the world have an inherited deficiency in NGLY1, leading to a complex neurodevelopmental disorder. A family diagnosed at Emory thought their older affected daughter had cerebral palsy for most of her childhood. How the loss of an enzyme that removes sugar tags from certain proteins causes problems is still being uncovered.

More broadly, geneticists can read a family’s DNA sequences and find the differences, but figuring out what they mean is still a challenge. That’s where the approach taken in a recent paper in Cell Systems, by Emory cell biologist Victor Faundez and colleagues at Illinois State, comes in.

His lab used a comparison of proteomes to dissect Menkes disease, a rare inherited deficiency in a copper transport enzyme called ATP7A. This means they didn’t compare genes; instead, they compared the proteins produced by patients’ cells with those in their unaffected relatives.

Copper is an essential part of the diet and can be found at the active sites of several enzymes. The symptoms of Menkes disease arise because of a lack of copper in the body, although cultured cells lacking ATP7A actually accumulate copper. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Navigating monstrous anticancer obstacles

A new PNAS paper from geneticist Tamara Caspary’s lab identifies a possible drug target in medulloblastoma, the most common pediatric brain tumor. Come aboard to understand the obstacles this research seeks to navigate. Emory library link here.

Standard treatment for children with medulloblastoma consists of surgery in combination with radiation and chemotherapy. Alternatives are needed, because survivors can experience side effects such as neurocognitive impairment. One possibility has emerged in the last decade: inhibitors of the Hedgehog pathway, whose aberrant activation drives growth in medulloblastoma.

Medulloblastoma patients are caught “between Scylla and Charybdis”: facing a deadly disease, the side effects of radiation and/or existing Hedgehog inhibitors. From Wikimedia.

As this 2017 Oncotarget paper from St. Jude’s describes, Hedgehog inhibitors are no fun either. In adults, these agents cause muscle spasms, hair loss, distorted sense of taste, fatigue, and weight loss. In a pediatric clinical trial, the St. Jude group observed growth plate fusions, resulting in short stature. The drug described in the paper was approved in 2012 for basal cell carcinoma, a form of cancer whose growth is also driven by the Hedgehog pathway. Basal cell carcinoma is actually the most common form of human cancer, although it is often caught at an early stage that doesn’t require harsh treatment.

Caspary’s lab studies the Hedgehog pathway in early embryonic development. In the PNAS paper, former graduate student Sarah Bay and postdoc Alyssa Long show that targeting a downstream part of the Hedgehog pathway may be a way to avoid problems presented by both radiation/chemo and existing Hedgehog inhibitors. Read more

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