Quinn Eastman

Lab Land looking back: Top ten themes for 2014

It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After diverting some of these topics into the 2015 crystal ball, I corralled them into themes.
1. Cardiac cell therapy
PreSERVE AMI clinical trial led by cardiologist Arshed Quyyumi. Emory investigators developing a variety of approaches to cardiac cell therapy.
2. Mobilizing the body’s own regenerative potential
Ahsan Husain’s work on how young hearts grow. Shan Ping Yu’s lab using parathyroid hormone bone drug to mobilize cells for stroke treatment.
3. Epigenetics
Many colors in the epigenetic palette (hydroxymethylation). Valproate – epigenetic solvent (anti-seizure –> anti-cancer). Methylation in atherosclerosis model (Hanjoong Jo). How to write conservatively about epigenetics and epigenomics.
4. Parkinson’s disease therapeutic strategies
Container Store (Gary Miller, better packaging for dopamine could avoid stress to neurons).
Anti-inflammatory (Malu Tansey, anti-TNF decoy can pass blood-brain barrier).
5. Personal genomics/exome sequencing
Rare disease diagnosis featured in the New Yorker. Three–part series on patient with GRIN2A mutation.
6. Neurosurgeons, like Emory’s Robert Gross and Costas Hadjpanayis, do amazing things
7. Fun vs no fun
Fun = writing about Omar from The Wire in the context of drug discovery.
No fun (but deeply moving) = talking with patients fighting glioblastoma.
8. The hypersomnia field is waking up
Our Web expert tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
Image guided cancer surgery (Shuming Nie/David Kooby). Cancer immunotherapy chimera (Jacques Galipeau). Fine tuning old school chemo drug cisplatin (Paul Doetsch)
10. Tie between fructose effects on adolescent brain (Constance Harrell/Gretchen Neigh) and flu immunology (embrace the unfamiliar! Ali Ellebedy/Rafi Ahmed)
Posted on January 7, 2015 by Quinn Eastman in Uncategorized Leave a comment

Point mutation in fragile X gene reveals separable functions in brain

A new paper in PNAS from geneticist Steve Warren and colleagues illustrates the complexity of the protein disrupted in fragile X syndrome. It touches on how proposed drug therapies that address one aspect of fragile X syndrome may not be able to compensate for all of them. [For a human side of this story, read/listen to this recent NPR piece from Jon Hamilton.]

Fragile X syndrome is the most common single-gene disorder responsible for intellectual disability. Most patients with fragile X syndrome inherit it because a repetitive stretch of DNA, which is outside the protein-coding portion of the fragile X gene, is larger than usual. The expanded number of CGG repeats silences the entire gene.

However, simple point mutations affecting the fragile X protein are possible in humans as well. In the PNAS paper, Warren’s team describes what happens with a particularly revealing mutation, which allowed researchers to dissect fragile X protein’s multifaceted functions. Read more

Posted on January 5, 2015 by Quinn Eastman in Neuro Leave a comment

A crystal ball for Lab Land: Top 5 topics in 2015

Alzheimer’s protein pathology

While a wise Dane once proposed that predictions are dangerous, especially concerning the future, it’s usually helpful to plan ahead. Here are five biomedical research topics we think will occupy our attention in 2015.

1. Alzheimer’s We’re hearing discordant music coming from Alzheimer’s researchers. Large pharmaceutical companies are shutting down clinical trials in frustration, but researchers keep coming forward with biomarkers that might predict future disease. This confusing situation calls for some new thinking. Allan Levey, Jim Lah and colleagues have been preparing the way for a “beyond the usual suspects” look at Alzheimer’s disease. We are looking forward to Levey’s appearance at the 2015 AAAS meeting and to drug discovery wizard Keqiang Ye’s continuing work on new therapeutic targets.

2. Ebola While the scare over Ebola in the United States may be over (we hope so!), the outbreak continues to devastate countries in West Africa. Clinical trials testing vaccines and experimental drugs are underway or will be soon. Read more

Posted on January 2, 2015 by Quinn Eastman in Uncategorized Leave a comment

Stem cell/cardiology researcher Hee Cheol Cho joins Emory

Please welcome stem cell/cardiology researcher Hee Cheol Cho to Emory. Starting in September, Cho joined the Wallace H Counter Department of Biomedical Engineering at Georgia Tech and Emory, and Emory-Children’s Pediatric Research Center. He and his team will focus on developing gene-and cell-based therapies for cardiac arrhythmias. Their research will adding to and complement the research of several groups, such as those led by Chunhui Xu, Young-sup Yoon, Mike Davis and W. Robert Taylor.

Cho comes from Cedars-Sinai Medical Center in Los Angeles, where he specialized in understanding cardiac pacemaker cells, a small group of muscle cells in the sinoatrial node of the heart that initiate cardiac contraction. These cells have specialized electrophysiological properties, and much has been learned in the last few years about the genes that control their development.

Cho and colleagues from Cedars-Sinai recently published a paper in Stem Cell Reports describing how the gene SHOX2 can nudge embryonic stem cells into becoming cardiac pacemaker cells. Read more

Posted on December 23, 2014 by Quinn Eastman in Heart Leave a comment

Connections between starvation and immunological memory

Researchers at Emory have been revealing several connections between cells’ responses to starvation and immunological memory. The latest example of this is a paper in Nature Immunology from Rafi Ahmed’s lab, showing that the cellular process of autophagy (literally: self-consumption) is essential for forming and maintaining memory T cells.

This finding has some practical implications for vaccination and could point the way to additives that could boost vaccine effectiveness in elderly humans. Researchers at Oxford have demonstrated that autophagy is diminished in T cells from aged mice, and T cell responses could be boosted in older mice using the autophagy-inducing compound spermidine. Read more

Posted on December 18, 2014 by Quinn Eastman in Immunology Leave a comment

Effects of cocaine exposure in adolescent rodents

Much of neuroscientist Shannon Gourley’s work focuses on the idea that adolescence is a vulnerable time for the developing brain. She and graduate student Lauren DePoy recently published a paper in Frontiers in Pharmacology showing that in adolescent rodents, cocaine exposure can cause the loss of dendritic arbors in part of the brain important for decision-making.

The researchers examined neurons in the orbitofrontal cortex, a region of the brain thought to be important for “linking reward to hedonic experience.” It was known that stimulants such as cocaine can cause the loss of dendritic spines: small protrusions that are critical for communication and interaction between neurons.

“To make an analogy, it’s like a tree losing some of its leaves,” Gourley writes. “Lauren’s work shows for the first time that if cocaine is given in adolescence, it can cause the loss of dendrite arbors – as if entire branches are being cut from the tree.”

The mice are exposed to cocaine over the course of five days in early adolescence, and then their behavior is studied in adulthood. This level of cocaine exposure leads to impairments in instrumental task reversal, a test where mice need to change their habits (which chamber they poke their noses into) to continue receiving food pellets.

The findings suggest a partial explanation for the increased risk of dependence in people who start using cocaine during adolescence.

Posted on December 17, 2014 by Quinn Eastman in Neuro Leave a comment

Frailty: we know it when we can measure it

One of Lab Land’s regular features is a post exploring a biomedical term that seems to be appearing frequently in connection with Emory research. This month I’d like to focus on frailty, which has been an important concept in treating elderly patients for some time. (This piece in The Atlantic nudged me into it.) Assessing frailty is emerging as a way for surgeons to predict post-operative complications.

Several teams of researchers have been trying to develop a standardized way of measuring frailty to aid in weighing the risks and benefits of surgery. Frailty may seem like a subjective quality (echoing Supreme Court Justice Potter Stewart’s remarks on obscenity: “I know it when I see it”) but if frailty can be defined objectively, doctors and patients can use it to help in decision-making.

Frailty can be thought of as a decrease in physiological reserve or a decrease in the ability to recover from an infection or injury. Much of the credit for developing the concept of frailty should go to Linda Fried, now dean of Columbia’s school of public health. While at Johns Hopkins, her team developed the Hopkins Frailty Score: a composite based on recent weight loss, self-reported exhaustion, low daily activity levels, low grip strength and slow gait. Read more

Posted on December 15, 2014 by Quinn Eastman in Uncategorized Leave a comment

The other “cho-” cardiovascular disease biomarker

Quick, what biomarker whose name starts with “cho-” is connected with cardiovascular disease? Very understandable if your first thought is “cholesterol.” Today I’d like to shift focus to a molecule with a similar name, but a very different structure: choline.

Choline, a common dietary lipid component and an essential nutrient, came to prominence in cardiology research in 2011 when researchers at the Cleveland Clinic found that choline and its relatives can contribute to cardiovascular disease in a way that depends upon intestinal bacteria. In the body, choline is part of two phospholipids that are abundant in cell membranes, and is also a precursor for the neurotransmitter acetylcholine. Some bacteria can turn choline (and also carnitine) into trimethylamine N-oxide (TMAO), high levels of which predict cardiovascular disease in humans. TMAO in turn seems to alter how inflammatory cells take up cholesterol and lipids.

Researchers at Emory arrived at choline metabolites and their connection to atherosclerosis by another route. Hanjoong Jo and his colleagues have been productively probing the mechanisms of atherosclerosis with an animal model. Very briefly: inducing disturbed blood flow in mice, in combination with a high fat diet, can result in atherosclerotic plaque formation within a few weeks. Jo’s team has used this model to examine changes in gene activation, microRNAs, DNA methylation, and now, metabolic markers.

Talking about this study at Emory’s Clinical Cardiovascular seminar on Friday, metabolomics specialist Dean Jones said he was surprised by the results, which were recently published by the American Journal of Physiology (to be precise, their ‘omics journal). The lead author is instructor Young-Mi Go. Read more

Posted on December 9, 2014 by Quinn Eastman in Heart Leave a comment

Going meta

Just before Thanksgiving, Slate writer Katy Waldman had a piece summarizing the growing body of evidence that linguistic metaphors reflect how we actually use our brains.

Emory neuroscientist Krish Sathian and his colleagues have been major contributors to this field (“conceptual metaphor theory”). In 2012, he and Simon Lacey published their brain imaging study, which found that when people listened to sentences involving touch metaphors (“having a rough day”), the parts of the brain involved in the sense of touch were activated. NPR’s Jon Hamilton talked about these findings with him in 2013.

At the recent Society for Neuroscience meeting, Sathian discussed his team’s ongoing work on how the brain processes metaphors that make references to body parts (head, face, arm, hand, leg, foot), as part of a nano symposium on language.

Posted on December 4, 2014 by Quinn Eastman in Neuro Leave a comment

Strategy to defend vs double hit at beginning of life

Chorioamnionitis is a complication of pregnancy: inflammation of the membranes surrounding the fetus, caused by a bacterial infection. It has the potential to inflict damage to the brain of the fetus, especially when combined with fetal hypoxia, and is a known risk factor for developing cerebral palsy.

Chia-Yi (Alex) Kuan and his team, who study fetal brain injury in the Department of Pediatrics, have a new paper in Journal of Neuroscience on a strategy for inhibiting fetal brain inflammation. Postdoctoral fellows Dianer Yang, Yu-Yo Sun and Siddhartha Kumar Bhaumik are co-first authors.

The researchers show that a type of immune cells called Th17 cells seems to be driving inflammation because the rest of the fetal immune system is still immature. A marker of Th17 cells is elevated in blood samples from human infants with chorioamnionitis, the researchers found. Th17 cells are thought to be important for both autoimmunity and anti-microbial responses.

A drug called fingolimod, which stops immune cells from circulating out of the lymph nodes, was effective in reducing inflammation-induced fetal brain injury in animal models. Fingolimod has been approved by the FDA for use with multiple sclerosis and has been studied in clinical trials of kidney transplantation. The authors write that it may be a potential add-on to hypothermia as a treatment for infants in danger of hypoxia + infection-induced brain damage.

Posted on December 4, 2014 by Quinn Eastman in Immunology, Neuro Leave a comment
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