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

Oct. 29, 2020

Research Roundup is a monthly feature that offers a sample of recent grants and publications for Emory faculty and staff. To suggest items for the November column, please email your submission to researchroundup@emory.edu by Nov. 9.

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:

Bench and translational research

Environmental, life science and public health research

Grants

NIH supports study of arginine therapy for sickle cell pain

Claudia R. Morris, professor of pediatrics at Emory School of Medicine and pediatric emergency medicine physician at Children’s Healthcare of Atlanta, received $8.7 million from the NIH to determine if giving additional arginine can reduce pain during a sickle cell pain crisis. Morris will lead a multicenter study of intravenous arginine therapy in collaboration with the Aflac Cancer and Blood Disorders Center of Children’s. Too little arginine, a type of amino acid that helps regulate normal blood flow, may cause blood vessels to constrict, reducing blood flow and contributing to sickle-related pain.

Klosky receives grant for HPV vaccine uptake intervention

James Klosky, professor of pediatrics at Emory School of Medicine and director of psychology for the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta, and University of Alabama colleague Wendy Landier were awarded a $1.8 million U01 grant from the National Cancer Institute. The study will evaluate the effectiveness and implementation of an intervention to increase HPV vaccine uptake among young cancer survivors.

Studying the evolutionary histories of people of the Americas

John Lindo, assistant professor of anthropology, received an NSF CAREER Award of $600,000 to lead investigations of the evolutionary and adaptive histories of Indigenous people of the Americas through his ancient DNA lab. The project will utilize population-level whole genomes from both ancient and modern individuals, along with comparative statistical and empirical methods, to reveal novel genomic features that may underlay adaptive phenotypes as they evolved through time, discover ancient migrations and determine the evolutionary impact of European contact on Indigenous populations.

The project includes an educational goal of bringing visiting scientists and scholars from Indigenous communities to the Emory lab, where they will work alongside Emory scientists and students and exchange knowledge, insights and perspectives.

Cedar Tree Foundation grant supports Center for Black Women’s Wellness

The Center for Black Women’s Wellness (CBWW) was recently awarded a $375,000 grant over three years from the Cedar Tree Foundation to implement the Black Women’s Environmental Wellness Project, in partnership with Emory’s Nell Hodgson Woodruff School of Nursing.

The initiative will protect African American women and children from toxic exposures through enhanced environmental health literacy. The award will allow CBWW to train staff, health care providers and community champions to educate community members on ways to reduce their exposures and protect their health.

Led by Jemea Dorsey, CEO of the CBWW, in partnership with Abby Mutic, assistant professor in Emory’s School of Nursing and director of the Southeast Pediatric Environmental Health Specialty Unit, the Black Women’s Environmental Wellness Project will also leverage the reach and resources of a network of partner organizations and launch a social media campaign to relay its messaging.

Testing botanical extracts for efficacy against SARS-CoV-2

Emory ethnobotanist Cassandra Quave received a $290,000 grant from the Marcus Foundation to lead an investigation of more than 2,000 botanical extracts for potential efficacy against the novel coronavirus SARS-CoV-2. Quave, an expert in plant-based medicines, is associate professor in Emory’s Center for the Study of Human Health and the School of Medicine’s Department of Dermatology.

The grant will fund tests to determine if any extracts can prevent SARS-CoV-2 from entering human cells in a laboratory dish. The samples will come from the Quave Natural Products Library, a repository of extracts derived from wild plants used in traditional medicine for infectious and inflammatory diseases and herbs used as dietary supplement ingredients.

Support for asylum and migration studies

Xochitl Marsilli-Vargas, assistant professor of Spanish in Emory College of Arts and Sciences, was awarded the Stanford Humanities Center (SHC) residential fellowship for the 2020-2021 academic year. During her tenure at the SHC, Marsilli-Vargas will advance her new project focused on asylum seekers, migration, language and the law.

She also received a Halle Institute-University Research Council (URC) International Research Award for the same period. With the support of the Halle Institute and URC, she will conduct research at the encampments of minors on the border between Tucson (Arizona) and Nogales, Mexico. 

Publications

Bench and translational research publications

Sequential therapy with pembrolizumab for Hodgkin lymphoma

Winship Cancer Institute oncologist Pamela Allen was lead author of a multicenter phase II study, published in Blood, showing a sequence of two approaches was effective and safe in patients with newly diagnosed classical Hodgkin lymphoma, including those with bulky disease. The combination was brief pembrolizumab monotherapy followed by AVD chemotherapy (doxorubicin, vinblastine and dacarbazine).

Muscle cell boundaries: Some assembly required

Emory cell biologist Guy Benian and colleagues have revealed proteins that help form muscle cell boundaries. In the worm C. elegans, they show how mutations cause junctions between muscle cells, which normally look like well-aligned zippers under the microscope, either not to form, or weaken and unravel. As a result, the mutant worms’ snake-like locomotion is impaired.

These particular mutations affect a protein called PIX-1, which localizes to structures called integrin adhesion complexes (IACs), which have an anchor-like function. Studying these proteins in humans may give insights into muscular dystrophies or cardiomyopathies. In mammals, similar PIX proteins were known to be important for brain and immune function; the current paper in Nature Communications provides the first evidence that PIX proteins have a function in muscle and are required for the assembly or stability of IACs.

The sweet side of Alzheimer’s proteomics

To gain new insights into the biology of Alzheimer’s, Emory investigators — led by pharmacologist Lian Li — mapped and cataloged alterations of proteins in Alzheimer’s and control brains, focusing on N-glycosylation. The results were published in Science Advances.

N-glycosylation is a chemical modification of many secreted or extracellular membrane proteins, involving the attachment of a branched tree of sugar molecules, and can influence a protein’s interactions or trafficking. The Li lab’s study, the first system-level view of human brain N-glycoproteins and in vivo N-glycosylation sites, identifies several brain proteins that are only N-glycosylated in Alzheimer’s or whose N-glycosylation is eliminated in Alzheimer’s. With additional work, the specific sites could become biomarkers or therapeutic targets.

Elevated troponin and cardiac risk prediction

High levels of troponin (a sign of acute stress to the heart) in the blood reveal whether someone recently experienced a heart attack, but lower levels of elevated troponin can be detected after strenuous exercise, even in healthy young athletes. With that response in mind, Emory Clinical Cardiovascular Research Institute investigators have been studying whether high-sensitivity troponin measurements might be used to replace cardiac stress tests.

A new paper in American Journal of Cardiology shows how elevated high-sensitivity troponin levels in response to exercise on a treadmill can predict future outcomes in patients with coronary artery disease — better than stress tests with imaging. The first author is cardiovascular research fellow Bruno Lima.

Reducing corticosteroid side effects

Steroid anti-inflammatory drugs such as dexamethasone and prednisone are widely used to treat conditions such as allergies, asthma, autoimmune diseases, cancer — and now, COVID-19. Yet they can have harmful side effects on the skin, bones and metabolism.

The side effects are thought to come from a molecular mechanism that is separate from the anti-inflammatory one, and scientists have envisioned that it may be possible to divide the two. A September 2020 paper in PNAS from Emory biochemist Eric Ortlund’s lab sketches out how one potential alternative may work.

Synthetic corticosteroids mimic the action of the stress hormone cortisol; both bind the glucocorticoid receptor (GR) protein. Ortlund’s group obtained structural information on how vamorolone, an experimental drug, sticks to the part of GR that binds hormones. Vamorolone is being developed for Duchenne muscular dystrophy.

Burning fat like a baby

Newborn humans and hibernating mammals have high levels of brown adipose tissue, which they use to generate heat. Adult humans generally don’t have abundant brown adipose tissue, even if they have lots of “white” fat. Increasing brown fat’s activity may be an approach to treat obesity and related metabolic disorders.

Researchers have identified an enzyme called Them1 (thioesterase superfamily member 1) as a factor that limits heat generation in brown adipose tissue. Emory biochemist Eric Ortlund and his lab showed how part of the Them1 enzyme binds a certain type of lipid molecule and also how that part of the enzyme anchors the enzyme close to lipid droplets in adipose cells. The results were published in PNAS. 

Improving old antibiotics vs. discovering new ones

Biomedical engineering researchers at Georgia Tech and Emory are tackling the problem of antibiotic resistance not by creating new drugs but by enhancing the safety and potency of ones that already exist.

Aminoglycosides are antibiotics used to treat serious infections caused by pathogenic bacteria like E. coli or Klebsiella. These antibiotics are used sparingly by doctors, in part because of the toxic side effects they can sometimes cause.

In research published in the journal PLOS One, Christopher Rosenberg, Xin Fang and senior author Kyle Allison demonstrated that lower doses of aminoglycosides could be used to treat bacteria when combined with specific metabolic sugars: glucose or mannitol. They showed that aminoglycoside-metabolite treatment significantly reduced the concentration of antibiotic needed to kill E. coli, Salmonella and Klebsiella.

Mutations sensitize cancers to PI3 kinase inhibitor class

Certain mutations sensitize breast and other tumors to a class of drugs inhibiting the p110α subunit of PI3 kinase, radiation oncologist Jennifer Spangle and colleagues report in PNAS.

Mutations in the PIK3CA gene are present in multiple cancer subtypes and can drive oncogenic transformation. One example of a p110α-selective inhibitor is alpelisib, approved by the FDA for metastatic breast cancer in 2019. Spangle joined Emory’s Department of Radiation Oncology as assistant professor and was first author of the paper from Dana Farber Cancer Institute/Harvard Medical School.

Galanin: The keep calm and carry on hormone?

The neuropeptide galanin appears to play subtly different roles depending on where it is expressed. In at least one part of the brain, it is tempting to call galanin the “keep calm and carry on” hormone, based on research from Emory neuroscientist David Weinshenker’s lab.

Emory graduate student Rachel Tillage’s paper in Journal of Neuroscience details how galanin’s production by a group of neurons in the locus coeruleus confers stress resilience in mice.

The paper shows that exercise increases galanin in the locus coeruleus, a region in the brainstem that produces the neurotransmitter norepinephrine. Also, galanin can provide protection against the anxiety-inducing effects of locus coeruleus activation.

Promoting angiogenesis in bone/wound healing

The natural processes of wound or bone healing rely on the growth of new blood vessels, or angiogenesis. If someone breaks a bone, it is standard practice to apply a cast and immobilize the broken bone, so that healing can proceed without mechanical distortion. After those initial stages of healing, applying surprising amounts of pressure can encourage angiogenesis, according to an August 2020 paper in Science Advances from biomedical engineer Nick Willett’s lab.

The data have implications directly on bone healing and more broadly on wound healing, he says. Willett’s lab is part of both Emory’s Department of Orthopedics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, and is based at the Atlanta Veterans Affairs Medical Center.

Environmental, life science and public health research publications

Collaborative care model for people with diabetes

A low-cost, one-year integrated or “collaborative” care model delivered in diabetes clinics can lower depressive symptoms and improve cardiometabolic health, researchers from Emory University, University of Washington and collaborators in India have found. The results were published in JAMA with principal investigator Mohammed K. Ali as first author of the paper. Ali is associate professor in the Hubert Department of Global Health at the Rollins School of Public Health.

In the INDEPENDENT (Integrating Depression and Diabetes Treatment) study, funded by the National Institute of Mental Health, researchers compared an integrated collaborative care model with usual care in 404 patients attending four diverse diabetes clinics in India over a two-year period and found major improvements in the group receiving the integrated approach.

HPV vaccine promotion within the church

Winship Cancer Institute and Emory investigators led by Robert Bednarczyk conducted a case study of HPV and HPV vaccine perceptions within an African Methodist Episcopal church. The study, published in Social Science & Medicine, could inform future health promotion efforts in other religious settings. 

Personality traits of conspiracy theorists

The Journal of Personality published research by Emory psychologists into the personality traits associated with those who self-report conspiratorial ideation. The analysis, titled “Looking Under the Tinfoil Hat,” was led by Emory graduate student Shauna Bowes, with the late Scott Lilienfeld, Emory professor of psychology, as senior author. Coauthors include Emory graduate student Thomas Costello and Emory undergraduate Winkie Ma.

Standardized personality surveys were administered to nearly 2,000 participants, who were also asked to rate the probable truth of various conspiracy theories. The results found links to conspiracy beliefs and a sense of entitlement, self-centered impulsivity, cold-heartedness, depressive moods and anxiousness. Another trait positively correlated to a belief in conspiracy theories was “psychoticism,” a pattern of thinking that is linked to increased vulnerability to psychosis. The authors conclude that future research should investigate how various personality variables may interact to predict conspiracy beliefs.

Access issues in Appalachia to proven opioid treatment

Despite its proven effectiveness as a treatment for opioid use disorders (OUD), buprenorphine is not reaching patients in central Appalachia, the epicenter of the opioid crisis in the United States, according to investigators from the Rollins School of Public Health.

The findings, published in the New England Journal of Medicine, were part of a National Institute on Drug Abuse–supported study in rural Kentucky. Substance-use disorders expert Hannah Cooper was first author of the perspective, with Emory coauthors David H. Cloud and April M. Young.

The researchers cite three main barriers that can account for pharmacists’ hesitation in dispensing the drug: an erosion of trust in physicians among pharmacists in the region, lingering stigma against people suffering from OUD, and wholesalers’ categorization of buprenorphine together with opioids. 

A new model for managing ecosystems across scales

Attempts to manage regional-scale environmental issues are becoming overwhelmed by recurring natural disasters such as increasing frequency and intensity of hurricanes and wildfires, not to mention global human health pandemics. Frontiers in Ecology and Environment published a review of a new approach to managing environmental problems across scales — known as panarchy — which engages law, policy and other sectors to help improve ecosystem management.

The review examines one of the first real-world efforts to implement panarchy in a social-ecological system: addressing the inability to sustain grasslands in the Great Plains of North America. The authors conclude that rigid perspectives focused on narrowly defined objectives often lead to undesirable outcomes and that the more holistic framework of panarchy offers a more promising way forward.

First author of the review is Emory alumnus Ahjond Garmestani, currently with the U.S. Environmental Protection Agency. Lance Gundersson, chair of Emory’s Department of Environmental Sciences, and Craig Allen, of the University of Nebraska, are among the coauthors. The three are now coediting a forthcoming book, “Applied Panarchy,” containing real-life examples of the new method. 

Stepwise approach to diabetes prevention

A study led by the Emory Global Diabetes Research Center suggests that a stepwise approach to preventing diabetes and identifying adults at risk of it is cost effective in India. The findings were published in JAMA Network Open.

Using data collected from 578 participants enrolled in a randomized clinical trial conducted in Chennai, India, researchers — led by epidemiologist Duygu Islek — conducted an economic evaluation, comparing lifestyle management practices plus metformin use with routine care from multipayer and societal perspectives. Findings showed that it would cost approximately $145 international dollars to screen for and reduce diabetes incidence by one percentage point, $14,539 international dollars per diabetes case prevented and/or delayed and $14,986 international dollars per quality-adjusted life-year gained. 

Sibling spillovers in disability: An economic study

Emory economist Krzysztof Karbownik was coauthor on an Economic Journal paper examining the effects of having a disabled younger sibling, using administrative data on children from both Florida and Denmark.

To address the identification challenge, the paper compares the differential effects for first- and second-born children in three-plus-child families, taking advantage of the fact that birth order influences the amount of time that a child spends in early childhood with their younger siblings, disabled or not. The paper finds evidence that, relative to the first born, the second child in a family is differentially affected when the third child is disabled.

Linking urban air pollution to COVID-19 deaths

A study published in The Innovation found a link between people living in areas where there is a prevalence of environmental factors, such as urban air pollution, and heightened incidences of COVID-19-related deaths. The study, led by Rollins School of Public Health researchers Donghai Liang and Liuhua Shi, was among the first published studies linking COVID-19 death outcomes to air pollution exposure in the United States.

The county-level data showed areas with higher rates of nitrogen dioxide — a pollutant linked to urban combustion sources, like traffic — experienced an 11.3 percent increase in COVID-19 case-fatalities and a 16.2 percent increase in COVID-19 mortalities. Counties in New York, New Jersey and Colorado showed the highest nitrogen dioxide levels. It is critical to continue enforcing air pollution regulations to protect public health, given that health effects occur even at very low concentrations, the authors said.

Preemptive COVID-19 testing in long-term-care facilities

In collaboration with the Fulton County Board of Health, Emory researchers found that testing for COVID-19 in long-term-care facilities before cases were known to occur resulted in lower overall COVID-19 cases. The results of the study were recently published in CDC’s MMWR Early Release report.

Senior author Sarita Shah says that the study provides data to support the need for proactive testing. Mass testing for COVID-19 has been an effective strategy for identifying asymptomatic and presymptomatic infections, but this study added support for a proactive approach to find cases early and prevent potential outbreaks among this vulnerable population. 

Limitations of symptomatic COVID-19 testing in jails and prisons

Mass testing events in 16 prison and jail facilities within the United States demonstrated that rates of COVID-19 were much higher than previously reported, increasing the total number of known cases in those detention facilities studied from 642 to 8,239.

Study coauthor Anne Spaulding, associate professor in the department of epidemiology at the Rollins School of Public Health, urged the need for broad testing in correctional facilities, including in Georgia, which does not routinely conduct mass testing in its prisons. The results of the study were published in CDC’s August 21 MMWR report. 

New insight into how life may have originated

Chemists gained a surprising new insight into how organic chemical reactions could have started inorganically, perhaps leading to the first life forms on Earth. The findings were published in Nature Chemistry.

Chemistry graduate student Trent Stubbs completed the work while he was an undergraduate at Furman University working in the lab of Greg Springsteen. They collaborated with coauthors Mahipal Yadav and Ram Krishnamurthy from the Scripps Research Institute.

The researchers focused on a central metabolic process, the citric acid cycle, as a potential kick- starter for life around 3.5 billion years ago. They zeroed in on the two smallest alpha-ketoacids involved in this cycle, pyruvate and glyoxylate, to simplify their approach to “booting up” a potential metabolic fossil. They added these alpha-ketoacids to water and warmed them up to conduct experiments. That led to the surprising observation that while glyoxylate acted as a raw material in the reaction, it also facilitated the pathway by serving as a source of electrons.

While the work does not prove how the citric acid cycle originated, it demonstrates that a simpler protometabolism could have emerged under prebiotically plausible conditions. It also provides clues for how the rise of metabolism may have made life possible by providing a flux of energy for the precursors of cells. More immediately, the discovery can be used to synthesize diagnostic agents used to detect cancer and bacterial infections, a method known as metabolic flux analysis. Stubbs and Springsteen filed for patents resulting from the research and cofounded a company called Aconabolics, LLC to generate the diagnostic tools.

Benefits of proactive COVID-19 testing in homeless shelters

People experiencing homelessness are particularly vulnerable to COVID-19 due to their lack of access to health care. Many of them have untreated chronic conditions that put them at a higher risk for contracting the virus. Emory researchers, including Jane Yoon and Sarita Shah, in collaboration with the CDC and Fulton County Board of Health, have found that proactive testing for COVID-19 among the homeless population before an outbreak resulted in lower overall COVID-19 cases. 

Facility-wide testing in congregate settings allowed for identification and isolation of COVID-19 cases and is an important strategy to interrupt SARS-CoV-2 transmission, the authors write. Additionally, the study found that people experiencing homelessness living in shelters experienced higher SARS-CoV-2 prevalence compared with those living unsheltered. The results were published in Clinical Infectious Diseases.

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