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

July 15, 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 August column, please email your submission to researchroundup@emory.edu by July 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 and technology licensing highlighted:

 

Grants

 

Winship investigator leading glioblastoma clinical study

Brain cancer researcher Renee Read received a two-year, $500,000 grant from the Ben & Catherine Ivy Foundation to support glioblastoma clinical research.

The project involves a Phase I/II clinical trial of the drug verteporfin (FDA-approved for macular degeneration) in patients with glioblastoma multiforme, the most common and deadly primary brain tumor in adults. This is the first-in-human glioblastoma trial of verteporfin, which Read’s lab had identified as a potential therapeutic acting on YAP and TAZ transcription factors.

The investigative team includes Winship Phase I Clinical Trials Unit director R. Donald Harvey, neurosurgeon Jeffrey Olson, medical oncologist William Read and postdoctoral fellow Se-Yeong Oh. More information is available here.

 

NSF grant to support antifungal research

Bill Wuest and colleagues in the Department of Chemistry were awarded a $429,000 grant from the National Science Foundation to study new agricultural chemicals and pesticides and develop teaching and training programs for graduate students. The goal of the project is to investigate antifungal natural products with potential against blight – in particular, promysalin and peniciaculin A, which appear to act on plant pathogens as mimics of the metabolic cofactor ubiquinone.

 

Antiviral drugs being repurposed for SARS-CoV-2

Remdesivir is one example of an antiviral drug developed for another target (Ebola) that is being repurposed to fight SARS-CoV-2.

To look for others, Emory investigators Baek Kim and Raymond Schinazi in the Department of Pediatrics were recently awarded a supplementary grant by the National Institute of Allergy and Infectious Diseases. The one-year, $312,000 supplement will support their efforts to screen for viral RNA polymerase inhibitors using the chemical library developed by Schinazi. The supplement takes advantage of an existing grant (Structural & Chemical Analysis of Highly Potent ALLINI) and established SARS-CoV-2 assay systems.

 

How a deadly bacterium spreads in host

Emory College’s departments of physics and biology and the School of Medicine received a $300,000 seed grant to characterize the molecular regulation of Acinetobacter baumannii phenotypes to understand its spread dynamics within a host.  The two-year award is from Emory’s basic science initiative From Molecules and Pathogens to Populations and Pandemics (MP3).

Acinetobacter baumannii is responsible for numerous outbreaks across the globe. Recently, it emerged as one of the most serious threats due to the prevalence of antibiotic resistance. Researchers found that A. baumannii displays two different phenotypes specialized in host colonization and environmental persistence. This project aims to uncover how the pathogen regulates its phenotypes to spread in a host community. The project will span molecular genetics; single-cell fluorescence microscopy; high-throughput flow cytometry measurements of infection; and mathematical multi-scale modeling. The long-term goal is to manipulate phenotypic switching to control A. baumannii infections.

The principal investigator is Minsu Kim, associate professor in Emory College. Co-PIs are Phil Rather, professor in the School of Medicine; Daniel Weissman, assistant professor in Emory College; and Nic Vega, assistant professor in Emory College.

 

Human contact and mobility shaping disease risk

Researchers from Rollins School of Public Health, Emory College’s Department of Computer Science and the Centers for Disease Control (CDC) and Prevention received a $250,000 seed grant to develop a new platform to model infectious disease transmission. The two-year award is from Emory’s basic science initiative From Molecules and Pathogens to Populations and Pandemics (MP3).

Patterns of human contact in households, in communities and across regions determine how infectious diseases spread and modulate the impact of control measures. However, the understanding of how human contact and disease shape risk is limited. This project will develop a platform integrating human contact and mobility data with infection history to build tractable, realistic models of disease transmission. The range and utility of the platform will be demonstrated by modeling geographic variation in rotavirus incidence post-vaccine introduction; and social distancing and travel restrictions to reduce spread of SARS-CoV-2.

The principal investigator is Benjamin Lopman, professor at Rollins School of Public Health. Co-PIs are Ymir Vigfússon, assistant professor in Emory College; Jan Vinje from the CDC; and Kristin Nelson, assistant professor at Rollins.

 

Macrophages in HIV transmission and persistence

Emory School of Medicine and the CDC received a $250,000 seed grant to seek insights into the role of macrophages in HIV transmission and persistence. The two-year award is from Emory’s basic science initiative From Molecules and Pathogens to Populations and Pandemics (MP3).

Macrophages are large white blood cells that are an important part of the immune system. The funded project will experiment with macaque SIV models of HIV exposure and persistence to assess the role of macrophages in HIV transmission, persistence during antiretroviral therapy (ART) and post-ART viral rebound. The experiments will assess macrophage-mediated HIV transmission in the presence or absence of rectal syphilis and whether latently infected macrophages reinitiate viral replication following ART cessation. The data will inform strategies to reduce HIV incidence through viral eradication and preventing transmission.

The principal investigator is Matthew Parsons, assistant professor in the School of Medicine. Co-PIs are Mirko Paiardini, associate professor in the School of Medicine, and Janet McNicholl from the CDC.

 

Fecal transplantation trial and antimicrobial resistance

Emory School of Medicine and Rollins School of Public Health received a $200,000 seed grant to assess fecal microbiota transplantation (FMT) for eradicating multi-drug resistant organisms (MDROs). The two-year award is from Emory’s basic science initiative From Molecules and Pathogens to Populations and Pandemics (MP3).

Small, observational studies show that FMT is up to 87.5 percent effective in eradicating MDRO colonization but the mechanisms of how FMT works in this process are poorly understood. This project builds a collaboration between the School of Medicine and Rollins with a phase I trial of FMT for MDRO decolonization. The data will serve as a springboard to understand mechanisms of FMT to interrupt MDRO transmission in populations.

The principal investigator is Michael Woodworth, assistant professor in the School of Medicine. Co-PIs are Colleen Kraft, associate professor in the School of Medicine, and Max Lau, assistant professor at Rollins.

 

Characterizing hybrid schistosomes in Tanzania

Emory College’s Department of Biology and Rollins School of Public Health received a seed grant for almost $200,000 to characterize the extent and epidemiological impact of hybrid schistosomes in Tanzania. The two-year award is from Emory’s basic science initiative From Molecules and Pathogens to Populations and Pandemics (MP3), aimed at taking a comprehensive, cross-disciplinary approach to the threat of emerging and re-emerging infectious diseases.  

Human schistosomes, blood flukes transmitted via freshwater snails, impose major, yet neglected human morbidity globally. Transmission occurs in ecologically complex communities. Recent documentation of hybrid schistosomes, arising from cattle- and human-specialists, overturns conventional wisdom and challenges existing control measures. Hybrids are more virulent and infectious than the parental species and can backcross and persist in humans.

This project will characterize the prevalence and distribution of human-cattle hybrid schistosomes, identify their drivers and assess their relevance for schistosome eradication.

The principal investigator is David Civitello, assistant professor in Emory College. The co-PI is Matthew Freeman, associate professor in Rollins School of Public Health.

 

Publications and technology licensing:

 

Antisense treatment for ALS hitting target, with early efficacy signs

An experimental gene-silencing drug designed for a rare, inherited form of amyotrophic lateral sclerosis (ALS) has shown promise in a clinical trial conducted at the Emory ALS Center and other medical centers around the world.

The trial indicated that the “antisense” drug, known as tofersen, lowers levels of a disease-causing protein in people with a type of ALS caused by mutations in the gene SOD1. The results of the study, published in New England Journal of Medicine, have led to the launch of a phase 3 clinical trial to further evaluate the safety and efficacy of tofersen. ALS is a progressive neurodegenerative disease affecting motor neurons.

Although the study was primarily designed to evaluate safety and whether the drug lowers levels of the target protein, there is preliminary evidence that high doses of tofersen slowed clinical progression of the disease, according to Jonathan Glass, director of the Emory ALS Center. More information about the study is available here.

 

Smart phones as exercise coach in peripheral artery disease

Cardiologists and public health researchers are continuing the Smart Step Study, which evaluates a smartphone-based, home exercise program for patients with peripheral artery disease (PAD). Walking short distances is painful for people with PAD, and supervised exercise is recommended. The Smart Step Study tests whether a FitBit movement tracker and phone apps could also encourage and enable patients to walk for longer distances.

Arash Harzand, Nanette Wenger, Amit Shah and colleagues published preliminary findings and the study’s rationale and design in the journal Clinical Cardiology. Participants are recruited from vascular and cardiology clinics at Grady Memorial Hospital, and enrollment is expected to continue until the end of the year, according to Shah.

 

Success in extending immunity against HIV

In a pre-clinical study with rhesus macaques, Yerkes and Emory Vaccine Center researchers showed that a new adjuvant (vaccine additive) helps induce long-lasting immunity against HIV’s close relative SIV. The results were published in Science Immunology.

Sudhir Pai Kasturi, assistant professor of pathology and laboratory medicine, was the first author of the paper. Emory Vaccine Center director Rafi Ahmed was co-senior author, along with former colleague Bali Pulendran, now at Stanford.

The adjuvant is based on the synthetic molecule 3M-052, which targets innate immune receptors TLR7 and TLR8. As part of a vaccine, nanoparticles carrying 3M-052 could induce antibody-producing plasma cells, which were maintained in the bone marrow for more than one year after vaccination. The research data from this study has prompted a Phase I clinical trial to assess the potential of 3M-052 in the context of HIV Env antigens.

A related paper on T cell immune responses from the same adjuvant-vaccine combination was published in Nature Medicine.

 

Harnessing plasma cells to fight COVID-19

The immune systems of recovered COVID-19 patients represent hidden treasure: plasma cells produce antibodies that could be harnessed to treat others. But those cells are rare and difficult to culture outside the body.

A California biotechnology company, Berkeley Lights, has licensed technology developed by Emory immunologist Frances Eun-Hyung Lee, assistant professor of medicine, which allows scientists to culture plasma cells more reliably. Lee is part of a Global Emerging Pathogen Antibody Discovery Consortium, which also includes investigators from Vanderbilt and La Jolla Institute for Immunology. More information is available here.

 

Advising psychology to embrace unpopular ideas

Scott Lilienfeld, Emory professor of psychology, wrote an introduction for a special issue of the Archives of Scientific Psychology on unorthodox ideas. In the article, Lilienfeld argues that psychology should more actively embrace unpopular ideas and that the field at large has not typically done enough to promote heterodoxy.

Reasons Lilienfeld cites for paying attention to challenging ideas include: They force closer scrutiny of long-standing assumptions; they can help uproot preconceptions; they can increase intellectual humility and the willingness to tolerate ideological diversity; and they help in the development of thicker intellectual skins. Finally, he notes that heterodoxy can help to combat “zombie ideas” within popular psychology that persist despite “remarkably feeble evidentiary bases.”

The special issue includes 16 articles challenging conventional wisdom in psychology on a range of topics. “Be prepared to have your feathers ruffled and your assumptions questioned and promise yourself only that you will approach each of these provocative articles with an open mind,” Lilienfeld advises readers.

 

Predicting cardiac risk through stress test brain imaging

Greater activation of a region of the brain involved in processing mental stress can predict future complications in people with coronary artery disease, a study from Emory Clinical Cardiovascular Research Institute found.

In 148 people with coronary artery disease, activation of the rostromedial prefrontal cortex (rmPFC) during a mental stress test was associated with greater risk of death, heart attack or cardiac hospitalization over the next three years. The risk also was connected with a stress-induced cytokine (IL-6) and heart rate variability.

Cardiovascular research fellow Kasra Moazzami was the first author, with Amit Shah, assistant professor of epidemiology at Rollins School of Public Health and medicine (cardiology) at Emory University School of Medicine, as senior author. The results were published in Circulation.

 

Thrombectomy study in Brazil

Endovascular clot removal therapy, known as thrombectomy, has been effective in reducing stroke-related disability in high-income countries. A study conducted in Brazil showed similar effectiveness in patients treated within eight hours after the onset of symptoms of a large vessel occlusion. 

The new study demonstrates that the benefits of stroke thrombectomy could be reproduced in a resource-limited healthcare system, and was published in New England Journal of Medicine. 

The trial showed that among 300 patients in the study, 90-day functional outcomes were better with thrombectomy plus standard care than with standard care alone. Specifically, the percentage of patients with a score on the modified Rankin Scale (mRS) 0–2 was 35.1 percent in the thrombectomy group, and 20 percent in the control.

The research was led by Raul Nogueira, professor of neurology, neurosurgery and radiology at Emory University School of Medicine and director of neuroendovascular service for Grady Health System. Nogueira also led the multi-center study that established stroke thrombectomy as standard of care in the United States in 2018.

 

T cell responses and controlling asymptomatic TB

A study of T cell responses against the bacteria that cause tuberculosis will be important for designing better vaccines and treatments to control the disease. Emory researchers showed that T cell responses emerged as early as three weeks post infection, and were critical in controlling latent/asymptomatic tuberculosis. The study results appeared in JCI insight.

Jyothi Rengarajan, associate professor of medicine in the Division of Infectious Diseases, was the lead author. Rengarajan and Yerkes researchers Uma Shanmugasundaram and Vijayakumar Velu worked with colleagues at Southwest National Primate Research Center, Texas Biomedical Research Institute and Tulane University.

In the study, the researchers worked with a non-human primate model of aerosol TB, comparing responses of CD4 and CD8 T cells in blood, airways and lungs. The researchers found higher frequencies of T cell responses in the airways and lungs than in blood. More information is available here.

 

Men’s perception of male and female infant cries

The Journal of Reproductive and Infant Psychology published a study by Emory anthropologists aimed at determining why male infants are subject to abuse, such as shaken baby syndrome, more frequently than female infants.

In experiments, adult males rated auditory and video cry stimuli from male infants and female infants for aversiveness. Crying bouts are primarily made up of exhaled and inhaled vocalizations, along with pauses. The results showed that the crying bouts of male infants produced more exhaled vocalizations; this variable correlated with higher aversiveness ratings.

Including visual stimuli increased male, but not female, infant cry aversiveness compared with audio stimuli alone. The findings suggest that both infant crying patterns and their visual appearance when crying may contribute to male infants’ increased vulnerability to abuse. The researchers hope the findings may help in the development of interventions for fathers to prevent infant abuse.

Lynnet Richey, a recent Emory graduate and a research specialist in the Department of Anthropology, is first author of the study. James Rilling, professor and chair of anthropology, is senior author. Ting Li, former research specialist in the Department of Anthropology, is co-author.

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