Quinn Eastman

Combined MR/PET imaging

On Thursday, April 8, Emory’s Center for Systems Imaging, directed by Department of Radiology Chair Carolyn Meltzer, MD, and the Atlanta Clinical & Translational Science Institute celebrated the launch of the CSI’s prototype MR/PET imaging scanner.

View of MR/PET

View of MR/PET scanner from front, with Ciprian Catana of MGH and Larry Byars of Siemens

The scanner is one of four world-wide and one of two in the United States, and permits simultaneous MR (magnetic resonance) and PET (positron emission tomography) imaging in human subjects. This provides the advantage of being able to combine the anatomical information from MR with the biochemical/metabolic information from PET. Potential applications include functional brain mapping and the study of neurodegenerative diseases, drug addiction and brain cancer.

Thursday’s event brought together leaders of the three other MR/PET programs in Boston, Jülich and Tübingen, the Siemens engineers who designed the device, and the Atlanta research community to explore the possibilities of the technology.

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Two birds with one stone in treatment of Alzheimer’s

Allan Levey, MD, PhD

The drugs now available to treat Alzheimer’s address the symptoms of the disease — memory problems — rather than the underlying mechanism of neurodegeneration.

But what if something could do both? Here’s a tantalizing prospect, hinted at by a long-running thread of brain research: compounds that boost the function of certain acetylcholine circuits in the brain might also modify production of toxic beta-amyloid protein.

Emory neurologists Allan Levey and Jim Lah and members of their laboratories have been working on this idea, together with Jeffrey Conn’s group at Vanderbilt, for several years.

James Lah, MD, PhD

The possibility grows out of the properties of certain receptors for the neurotransmitter acetylcholine, called “muscarinic acetylcholine receptors.” Acetylcholine is a major transmitter of signals in the brain, and there are several varieties of receptors, or receiver dishes for the signals, on brain cells.

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Biomarker may predict serious complications after lung transplantation

Researchers at Emory studying lung transplantation have identified a marker of inflammation that may help predict primary graft dysfunction (PGD), an often fatal complication following a lung transplant.

Primary graft dysfunction after a lung transplant

The results are published in the American Journal of Transplantation. First author Andres Pelaez, a pulmonary medicine specialist at Emory’s McKelvey Lung Transplant Center, and postdoc Patrick Mitchell led the research team.

“Despite major advances in surgical techniques and clinical management, serious lung transplant complications are common and often untreatable,” Pelaez says. “PGD is a severe lung injury appearing just a few days after transplantation. Unfortunately, predicting which lung transplant recipients go on to develop PGD has been so far unsuccessful. Therefore, our research has been directed towards identifying predictive markers in the donor lungs prior to transplantation.”

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How intestinal bacteria influence appetite, metabolism

Pathologist Andrew Gewirtz and his colleagues have been getting some welldeserved attention for their research on intestinal bacteria and obesity.

Briefly, they found that increased appetite and insulin resistance can be transferred from one mouse to another via intestinal bacteria. The results were published online by Science magazine.

Previous research indicated intestinal bacteria could modify absorption of calories, but Gewirtz and his colleagues showed that they influence appetite and metabolism (in mice)

“It has been assumed that the obesity epidemic in the developed world is driven by an increasingly sedentary lifestyle and the abundance of low-cost high-calorie foods,” Gewirtz says. “However, our results suggest that excess caloric consumption is not only a result of undisciplined eating but that intestinal bacteria contribute to changes in appetite and metabolism.”

A related report in Nature illustrates how “next generation” gene sequencing is driving large advances in our understanding of all the things the bacteria in our intestines do to us.

Gewirtz’s laboratory’s discovery grew out of their study of mice with an altered immune system. The mice were engineered to lack a gene, Toll-like receptor 5 (TLR5), which helps cells sense the presence of bacteria.

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Probing a puzzling form of muscular dystrophy

Two researchers at Emory, Anita Corbett and Grace Pavlath, recently have combined their expertise to probe how a puzzling form of muscular dystrophy develops.

Oculopharyngeal muscular dystrophy (OPMD) is an inherited type of muscular dystrophy that primarily affects muscles of the face and throat. In the video below, Anita Corbett explains how this affects patients as they get older.


The mutations that cause the disease make a protein called PABPN1 longer and stickier than normal, and the mutated protein appears to form clumps in muscle cells.

The puzzle lies in that PABPN1 (poly A binding protein nuclear 1) can be found everywhere in the body, but it’s not clear why the mutated protein specifically affects muscle cells — or why the muscles in the face and throat are especially vulnerable.

In December 2009, Corbett, Pavlath and postdoctoral fellow Luciano Apponi published a paper where they suggest that the clumps of mutated protein, which some researchers have proposed to be toxic, might not be the whole story. A lack of functioning PABPN1 might be just as strong a factor in the disease, they’ve discovered.

The results will appear in a future issue of the journal Human Molecular Genetics.

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Nanotechnology may help surgeons detect cancer

What a cancer patient wants to know after surgery can be expressed succinctly: “Did you get everything?” Having a confident answer to that question can be difficult, because when they originate or metastasize, tumors are microscopic.

Considerable advances have been made in “targeted therapy” for cancer, but the wealth of information available on the molecular characteristics of cancer cells hasn’t given doctors good tools for detecting cancer during surgery – yet.

Even the much-heralded advent of robotic surgery has not led to clear benefits for prostate cancer patients in the area of long-term cancer control, a recent New York Times article reports.

At Emory and Georgia Tech’s joint department for biomedical engineering, Shuming Nie and his colleagues are developing tools that could help surgeons define tumor margins in human patients.

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A new class of brain-protecting drugs

Pathologist Keqiang Ye has made a series of discoveries recently, arising from his investigations of substances that can mimic the growth factor BDNF (brain-derived neurotrophic factor).

BDNF is a protein produced by the brain that pushes neurons to withstand stress and make new connections. Some neuroscientists have described BDNF as “Miracle Gro for brain cells.”

“BDNF has been studied extensively for its ability to protect neurons vulnerable to degeneration in several diseases, such as ALS, Parkinson’s and Alzheimer’s disease,” Ye says. “The trouble with BDNF is one of delivery. It’s a protein, so it can’t cross the blood-brain barrier and degrades quickly.”

Working with Ye, postdoctoral fellow Sung-Wuk Jang identified a compound called 7,8-dihydroxyflavone that can duplicate BDNF’s effects on neurons and can protect them against damage in animal models of seizure, stroke and Parkinson’s disease. The compound’s selective effects suggest that it could be the founder of a new class of brain-protecting drugs. The results were published in Proceedings of the National Academy of Sciences.

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Peripheral artery disease: can help come from the bone marrow?

Peripheral artery disease affects millions of people in the United States. It’s basically hardening of the arteries (atherosclerosis) leading to problems with getting enough blood to the limbs. Symptoms of severe PAD include leg pain that doesn’t go away once exertion stops and wounds that heal slowly or not at all.

Lifestyle changes, medication and surgery can address some cases of PAD, but often the disease is not recognized until it has advanced considerably. At Emory, cardiologist Arshed Quyyumi has been exploring whether a patient’s own bone marrow cells can repair the arteries in his or her limbs.

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Creating tools for next-generation sequencing

Emory biochemist Eric Ortlund participated in a study that was recently published in Proceedings of the National Academy of Sciences, which involves tinkering with billions of years of evolution by introducing mutations into DNA polymerase.

What may soon be old-fashioned: next-generation sequencing combines many reactions like the one depicted above into one pot

DNA polymerases, enzymes that replicate and repair DNA, assemble individual letters in the genetic code on a template. The PNAS paper describes efforts to modify Taq DNA polymerase to get it to accept “reversible terminators.” (Taq = Thermus aquaticus, a variety of bacteria that lives in hot springs and thus has heat-resistant enzymes, a useful property for DNA sequencing)

Ortlund was involved because he specializes in looking at how evolution shapes protein structure. Along with co-author Eric Gaucher, Ortlund is part of the Fundamental and Applied Molecular Evolution Center at Emory and the Georgia Institute of Technology.

To sequence DNA faster and more cheaply, scientists are trying to get DNA polymerases to accept new building blocks. This could facilitate next-generation sequencing technology that uses “reversible terminators” to sequence many DNA templates in parallel.

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The importance of upbringing

Every time scientists identify genetic risk factors for a human disease or a personality trait, it seems like more weight accumulates on the “nature” side of the grand balance between nature and nurture.

That’s why it’s important to remember how much prenatal and childhood experiences such as education, nutrition, environmental exposures and stress influence later development.

At the Emory/Georgia Tech Predictive Health Symposium in December, biologist Victor Corces outlined this concept using a particularly evocative example: bees. A queen bee and a worker bee share the same DNA, so the only thing that determines whether an insect will become the next queen is whether she consumes royal jelly.

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