Research roundup: Recent grants and publications for Emory faculty and staff

March 12, 2020

Research Roundup is a monthly feature that offers a sample of recent grants and publications for Emory faculty and staff.

It is published the second Thursday of each month. To suggest items for the April 9 column, please email your submission to researchroundup@emory.edu by March 25.

As an academic research institution, Emory’s faculty and staff conduct studies across every discipline, from the sciences to the humanities. Here’s a sample of recent grant awards and the work they will support, plus highlights from some published research findings.

Grants highlighted:

Publications highlighted:

 


Grants


NINDS support of myotonic dystrophy work

The National Institute of Neurological Disorders and Stroke has awarded scientists at Emory, with colleagues at University of Florida, $2.2 million over five years to examine the neuronal function of Muscleblind-like proteins, which play key roles in myotonic dystrophy. Emory cell biology chair Gary Bassell and University of Florida neurogeneticist Eric Wang are collaborating on the project. 

Myotonic dystrophy is a multi-system disorder caused by expanded DNA triplet or quadruplet repeats. RNA from the expanded repeats is thought to bind and sequester Muscleblind-like proteins, leading to an impaired process of RNA splicing. Bassell says the research is expected to clarify how Muscleblind-like proteins regulate RNA localization in neurons, and also identify therapeutic targets for neurological aspects of myotonic dystrophy.

 

Electrical stimulation of cardiac stem cells

Researchers think cardiac stem cells could be used to treat congenital heart defects in children. Yet previous studies show that unless the cells are extracted before the age of one month, their therapeutic efficacy diminishes.

Joshua Maxwell, assistant professor in the Department of Pediatrics, received a five-year, $2 million grant to study whether electrically stimulating the stem cells before implantation can improve their function and retention. Maxwell is a member of the Children's Heart Research and Outcomes Center, part of the Children’s Healthcare of Atlanta/Emory/Georgia Tech pediatric research partnership. The grant is from the National Heart Lung and Blood Institute.


Optimizing neuromodulation and memory enhancement

Babak Mahmoudi, assistant professor of biomedical informatics at Emory University School of Medicine, received a four-year, $1.6 million grant to optimize electrical brain stimulation for memory enhancement. The grant is from the National Institute of Biomedical Imaging and Bioengineering.

Electrical stimulation of the amygdala has been shown to enhance memory in humans, but the process is far from optimized. Mahmoudi’s project will develop an open-source, end-to-end platform called NeuroWeaver to design, test and deploy intelligent closed-loop neuromodulation systems that will automatically learn optimal neuromodulation control policies by interacting with the nervous system. 


Early Career Award for modeling cell behavior

Denis Tsygankov, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, has received a Faculty Early Career Development  Award from the National Science Foundation. 

The five-year, $504,599 grant will focus on developing an integrative computational methodology enabling the comprehensive study of coordinated cell behavior, a process that plays a central role in embryonic development, wound healing and cancer invasion.


Immune effects of chronic social stress

Vasiliki Michopoulos is part of a project designed to examine the effects of chronic social stress on immune function. Michopoulos is an assistant professor of psychiatry and behavioral sciences and core scientist at Yerkes National Primate Research Center. 

Jenny Tung at Duke, recent MacArthur grant winner and leader of the $600,000-per-year project, and Michopoulos have extensive experience probing how social status in hierarchical non-human primates influences metabolic and immune function. The research, funded by the National Institute on Aging and split between Duke, Emory/Yerkes and University of Chicago, aims to address a key outstanding question: when, and for whom, are chronic social stress effects on immune function most important?

 

Publications


Basic and Translational Research


Supercharged viruses vs. triple-negative breast cancer

Engineered viruses that specifically kill cancer cells? Not new. But combining them with doxorubicin, a bright red-colored chemotherapy drug? Now we’re getting somewhere.

Bernardo Mainou, assistant professor of pediatrics, and colleagues generated novel reoviruses that were optimized to infect and kill triple-negative breast cancer cells in combination with topoisomerase inhibitors such as doxorubicin. The data was published in Journal of Virology.

Colorful commentary here.


Synthetic, self-adjusting aortic valve

Biomedical engineers used 3D printing to create an aortic valve model that can respond to physiological stress in a way that mimics how cardiac valves adjust in the body. The valve was made of a synthetic polymers scaffold, and incorporated mesenchymal cells that produce collagen and other proteins. The eventual goal is to produce a valve that can repair and remodel itself in a pediatric patient.

Former graduate student Aline Nachlas, from Mike Davis’ lab in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, is first author of the paper in Biomaterials. Davis is head of the Children’s Heart Research and Outcomes Center, part of the Children’s Healthcare of Atlanta/Emory/Georgia Tech pediatric research partnership.


Neurodegeneration and intestinal bacteria

An influential theory about the anatomical trajectory of Parkinson’s disease is getting a microbial boost. The idea, first proposed in 2003, is that pathology and neurodegeneration start in the intestines and then travel to the brain. Timothy Sampson, in Emory’s Department of Physiology, was first author on a recent paper in eLife, which explores the idea that prion-like proteins produced by intestinal bacteria can accelerate the aggregation of similar proteins found in our cells.

The findings suggest that interventions targeting intestinal bacteria could modulate neurodegeneration.

Sampson, a former Emory graduate student who did postdoctoral work at Caltech, says he is continuing the project at Emory. More information is available here.

 

Clinical, Public Health and Psychology Research


Meta-analysis of hypertension medications

A meta-analysis comparing various classes of antihypertension medications found that they had similar benefits, in terms of reducing cardiovascular events in patients without substantial co-morbidities. This knowledge could be important in designing cost-effective interventions against hypertension in developing countries. 

Mohammed Ali, associate professor of global health and epidemiology at Rollins School of Public Health, and colleagues conducted a meta-analysis of 46 randomized clinical trials, including almost 250,000 patients. The results were published in JAMA Network Open.

Major first-line antihypertension medications (including ACE inhibitors, calcium channel blockers, beta-blockers, angiotensin receptor blockers and diuretics) were all reported to be effective in reducing cardiovascular events compared with placebo. When compared to other antihypertension medications, ACE inhibitors appeared to be the medications of choice to prevent myocardial infarction, and diuretics appeared to be the optimal choice to reduce revascularization.

 

Prenatal stress and offspring depression risk

Maternal stress during pregnancy raises the risk of depression up to 20 years later in individuals with high genetic susceptibility, finds a recent study by Emory psychologists. It was already known that prenatal stress can alter the fetal hypothalamus-pituitary-adrenal axis, a phenomenon known as “fetal programming” that is associated with effects such as depression.

Patricia Brennan, chair of psychology, and Emory graduate student Brooke McKenna wanted to examine these effects into adulthood, when the risk for depression onset is highest. Their prospective, longitudinal study spanned two decades from pregnancy and indicated that prenatal stress interacted with genetic risk to predict depression in offspring. Their findings, published by Development and Psychopathology, provide the first evidence that genetic variants associated with the HPA axis may act to moderate the association between fetal programming and adult depression.

 

Brain metastases treatment

Results from an NRG Oncology clinical study, co-authored by Emory’s senior vice president for research Deborah Bruner, found that shaping radiation therapy so that it avoids hippocampal stem cells improves cognitive and patient-reported outcomes for patients with brain metastases.

The multicenter study enrolled 518 patients assigned to standard whole-brain radiotherapy or whole-brain radiotherapy avoiding the hippocampus. At six months, patients who received whole-brain radiotherapy with hippocampal avoidance reported less fatigue, less difficulty remembering things, less difficulty speaking and less interference of neurologic symptoms in daily activities. Results were published in the Journal of Clinical Oncology.


Patient-reported vs. clinician-reported radiotherapy outcomes

A study of 234 patients with cervical or endometrial cancer requiring postoperative radiation therapy showed differences in patient-reported effects of radiation. Deborah Bruner, senior vice president for research, was a co-investigator of the study published in the Journal of Clinical Oncology. 

Patient-reported adverse events showed a reduction in symptoms with intensity-modulated radiotherapy compared with standard radiotherapy, whereas clinician-reported adverse events revealed no difference. The authors suggest that patient-reported symptomatic gastrointestinal adverse events are important to assess in this disease setting.


Linking U.S. opioid and infectious disease epidemics

Emory infectious disease and opioid researchers have found that the opioid epidemic in the U.S. is simultaneously driving an infectious disease epidemic, including Hepatitis C, HIV/AIDS and other bacterial and sexually transmitted infections.

Carlos del Rio, professor of medicine and professor of global health at the Rollins School of Public Health and Hannah Cooper, professor at Rollins School of Public Health, contributed to the findings. The results are part of a new report from the National Academies of Sciences, Engineering and Medicine.


Couplings of hormones in women athletes

It's well known that testosterone and cortisol are coupled in male athletes but less was known about female athletes. Emory psychologist David Edwards and a colleague conducted a study with women on Emory’s varsity volleyball and soccer teams. The participants gave saliva samples in the run-up to, and over the course of, two different intercollegiate contests.

Analyses showed estradiol as being significantly coupled with testosterone, which was also coupled with cortisol. PeerJ published the results, the first report of significant within-person coupling between estradiol and testosterone in the context of competitive athletic stress.


Evaluating immune checkpoint inhibitors

Some of the most widely used and effective cancer immunotherapy agents have the potential to rev up the immune system enough to drive cardiac adverse events.

Anant Mandawat, head of Winship Cancer Institute’s cardio-oncology clinic, and several international collaborators evaluated global longitudinal strain (a sensitive cardiac marker measured by echocardiography) and its association with cardiac events in patients receiving immune checkpoint inhibitors. 

The conclusions support use of GLS as a risk marker for cardiac toxicity in patients receiving immune checkpoint inhibitors. The results were published in the Journal of the American College of Cardiology. 

 

Inequities with insulin pumps in pediatric diabetes

Emory sociologist Cassidy Puckett and colleagues studied two pediatric diabetes clinics that differed substantially in how they provide insulin pumps to patients. How the two clinics were organized and attitudes to medical technology among clinical staff influenced insulin pump use. Variation in how clinicians frame technologies—as risky, neutral or beneficial—and the stance of requiring patients to “earn” access to them can create inequities, Puckett says. 

The findings were published in Social Science and Medicine. Endocrinologists Kristina Cossen and Tanicia Daley in Emory’s Department of Pediatrics and Jenise Wong at the University of California, San Francisco were co-authors.

 

Technology and inequality in Chicago schools

In work published in Harvard Educational Review, assistant professor of sociology Cassidy Puckett uses Chicago schools as a lens for examining technology and inequality in the context of education. Chicago recently instituted a computer science course as a high school graduation requirement, in response to a national initiative called CS4All (Computer Science for All).

Puckett drew upon survey data to show that Chicago students varied widely in their technology learning readiness and that while families shape readiness, schools largely do not. The study suggests the need for intervention before high school, Puckett concludes.

 

Debate on management of acute severe hypertension

Philip Shayne, professor of emergency medicine and assistant dean for graduate medical education at Emory, was co-author on a Feb. 13 letter commenting on management of acute severe hypertension in the New England Journal of Medicine.

A recent review in NEJM on acute severe hypertension generated some debate. In their letter, Shayne and co-author Aaron Sibley, from University of Prince Edward Island, caution against immediate lowering of blood pressure in the absence of target-organ damage. This approach has not been shown to reduce adverse short-term outcomes, but may result in unpredictable changes in blood pressure and unnecessary referrals from primary care physicians, Shayne and Sibley write.

 

Music Research

 

Inside the Sacred Harp experience

A new publication—an article and three immersive audiovisual recordings—uses 360-degree recording equipment to take readers inside Sacred Harp’s “hollow square.” The publication is in the journal Southern Spaces.

The hollow square is the space around which participants sit during this Southern traditional form of shape-note singing, organized by voice part and facing each other, as a procession of leaders take turns directing songs. The hollow square is the spatial, aesthetic and spiritual center of this international music culture with roots in Alabama, Georgia, Mississippi, Florida and Texas. These videos, recorded at the annual singing at Mt. Lebanon Baptist Church in west Alabama on June 23, 2019, provide new virtual access to the experience.

Co-authors Jesse P. Karlsberg and Steve Bransford are staff members at the Emory Center for Digital Scholarship, and Karlsberg is associated faculty in the Department of Music.

 

Physics Research

 

How dance of liquids leaves “fingers” or “pearls”

If you’ve ever looked at the shadow of a glass of wine, you may have noticed droplets forming at the top of the wine’s shadow. This ring of residue is known as “tears of wine,” or the Marangoni effect. It is due to the fact that alcohol has a lower surface tension than water. 

Lab members of Emory physicist Justin Burton wanted to understand more about how this dance of two liquids works to leave different patterns of residue. They experimented with drops of the solvent isopropyl alcohol mixed with solutes such as ethylene glycol or dodecane. The results showed that the residue pattern depends not just on the surface tension between the two liquids, but also the properties of the surface where the residue is deposited. A droplet on a clean glass slide spreads thinly, creating long fingers along its edges that show up in the residue. If the glass slide is less clean, with traces of oils and hydrocarbons, the droplet forms round protrusions like pearls at the edges and doesn’t spread as far. 

Physical Review Letters published the work, which could lead to new, cheaper ways to make thin films for semi-conductors and other applications.

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