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

Emory Report | Nov. 9, 2021

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As an academic research institution, Emory is home to faculty and staff who 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.

To read more about ongoing research at Emory, visit the eScience Commons blog (for natural and social sciences) and the Lab Land blog (for health sciences).

 

Grants highlighted:

  

Publications highlighted:

 

Grants

Using protein labeling technique for Alzheimer’s research

Scientists at Emory and Georgia Tech have received a five-year, $5.2 million grant from the National Institute on Aging to investigate mechanisms of Alzheimer’s disease using an innovative protein labeling method developed at Emory.

For the project, the researchers’ hypothesis is that excessive activation of the ERK signaling pathway is central to Alzheimer’s pathogenesis; they will use their protein labeling approach to test the hypothesis.

Neurologist Srikant Rangaraju and colleagues have developed a mouse model that allows proteins within specific cell types or regions of the brain to be labeled with biotin, a vitamin that is a convenient handle for biochemical analysis.

The approach could help researchers dissect the involvement of neurons and microglia in Alzheimer’s without having to isolate each cell type, because the biotin label can be engineered genetically to only appear in certain cell types or regions of the brain.

Additional investigators on the project are biochemist Nicholas Seyfried at Emory and systems biologist Levi Wood at Georgia Tech.

 

A better understanding of cellular actin dynamics

Shashank Shekhar, assistant professor of physics in Emory College of Arts and Sciences, has been awarded a $1.94 million Maximizing Investigators' Research Award (MIRA) from the NIH’s National Institute of General Medical Sciences. 

The five-year award will fund Shekhar’s work to understand how cellular actin dynamics arise from the interplay between multicomponent protein ecosystems and mechanical forces. A member of the  Theory and Modeling of Living Systems (TMLS) Initiative at Emory, Shekhar combines mathematical modeling and single-molecule biophysical and biochemical experiments in his research. He joined the Emory faculty in August 2020.

 

Studying gender-based violence and violence against children

Emory researchers have been awarded a $1.35 million, five-year grant from the National Institutes of Health/Fogarty International Center to conduct trainings, develop prevention measures and build workforce capacity to tackle gender-based violence and violence against children in Vietnam.

The Emory-led Consortium for Violence Research, Implementation and Leadership Training for Excellence (CONVERGE) will be conducted in collaboration with researchers at the U.S. Centers for Disease Control and Prevention; Georgia State University; individual scholars based in Georgia, Europe and South Africa; and four partner universities in Vietnam: Hanoi Medical University, Ho Chi Minh University of Medicine, Hai Phong University of Medicine and Pharmacy and Hue University of Medicine and Pharmacy. More than 20 Emory faculty and alumni are affiliated with the project. The D43 international training grant was awarded to Kathryn Yount and Le Minh Giang, who will serve as co-directors of the training program. 

 

Linking environmental contaminants, liver disease and cancer

Joellen Schildkraut, epidemiologist at the Rollins School of Public Health, and colleagues in North Carolina have received a $1.1 million grant from the National Cancer Institute and the National Institute of Environmental Health Sciences to study liver cancer as part of the Southern Liver Health Study. The study is the first large-scale effort to longitudinally determine the link between environmental contaminants, liver disease and cancer in a residentially and ethnically diverse population. The Southern Liver Health Study plans to enroll to 16,000 males and females aged 40 years and older in North Carolina and Georgia.

Hepatocellular carcinoma (HCC) is one of the few cancers with increasing incidence in the U.S. Incidence of HCC has tripled since 1980, which is particularly worrisome given that HCC confers a median survival of less than two years. Researchers will test the overarching hypothesis that cadmium alone or in a mixture with other toxic metals and per/poly-fluoroalkyl substances increases the risk of progression from nonalcoholic fatty liver disease to liver fibrosis and cancer.

 

Predicting greenhouse gas emissions from terrestrial-aquatic interfaces

Debjani Sihi, assistant professor in the Department of Environmental Sciences, is the lead investigator of a project supported by a $300,000 award from the Department of Energy’s Environmental System Science Program. The title of the project is “Using probability distribution function as a scaling approach to incorporate soil heterogeneity into biogeochemical models for greenhouse gas predictions.”

Collaborators include Jianqiu Zheng from Pacific Northwest National Laboratory; Eric Davidson from the University of Maryland; Patrick Megonigal from Smithsonian Environmental Research Center; and Michael Weintraub from the University of Toledo. The goal of this multi-institution project is to improve predictions of greenhouse gases from freshwater and coastal wetlands using a novel approach that can scale microsite-scale processes to ecosystem-scale functions. See here for more information.

 

Soil carbon research across the U.S.

Emory researcher Debjani Sihi was awarded a $252,000 National Science Foundation grant to conduct soil carbon research. The grant is titled: “Upscaling soil organic carbon measurements at the continental scale: Evaluating emergent ecosystem properties using multivariate quantitative methods”. Samantha Weintraub from National Ecological Observatory Network is a co-investigator, with Jitendra Kumar from Ridge National Laboratory collaborating.

The project aims to provide a robust estimate of soil organic carbon for the conterminous United States (the “lower 48,” excluding Alaska, Hawaii, Puerto Rico and other territories) using a multivariate quantitative method. The product of this project will help identify potential reasons for inconsistency across different models and ultimately facilitate policymakers in making informed decisions about climate change. It will also offer research training opportunities for students as well as workshops and training courses for teachers.

 

Reproductive health among female cancer survivors

Pediatrics and nursing researcher Brooke Cherven has received a K23 career development award for $156,000 from the National Institute of Nursing Research. The grant will support Cherven’s patient-oriented research into the reproductive health needs of young adult female cancer survivors and identify decisional and contextual factors that influence fertility status assessments.

Cherven’s planned study will enroll 325 female survivors from four cancer centers in the United States to complete surveys and interviews.

 

Supplement to support pediatric cancer survivorship

Pediatrics researchers Jordan Gilleland Marchak and Karen Effinger have received a $150,000 P30 supplement to Winship Cancer Institute’s Cancer Center Support Grant to study how institutions can support childhood cancer survivors by improving the transition from the pediatric to adult care setting.

The findings from surveys will be used to inform organizational changes to improve transition support for childhood cancer survivors at Winship, and to develop a toolkit to help other cancer centers address organizational barriers to successful transition of childhood cancer survivor patients. Co-investigators are Ann Mertens, Natia Esiashvili and Traci Leong. 

 

Research publications

Investigating global public health shortcomings during COVID-19 pandemic

A number of faculty and students from Rollins School of Public Health are engaged with writing, editing and contributing to a forthcoming book aimed at investigating the shortcomings in global public health action that have emerged during the COVID-19 pandemic.

Research professor Scott McNabb and adjunct associate professor Carol Haley are among the 16 co-editors of the book “Modernizing Global Health Security to Prevent, Detect, and Respond,” slated for a mid-2022 release from Elsevier.  

More than 100 contributors — including partners at the World Health Organization and International Association of National Public Health Institutes — are involved in the project through scientific review, analyses and insight into the current gaps and impediments to global public health security, both as it relates to COVID-19 response and other pandemics.

Once complete, the book will provide scientific guidance and actionable solutions for public health leaders in future pandemics. 

 

The motivation connection between inflammation and depression

In a paper published recently in Pharmacological Reviews, Emory School of Medicine researchers outlined the impact of inflammation on motivation as it relates to depression. The authors proposed that low-grade inflammation affects brain chemicals and brain circuits that regulate motivation, ultimately leading to motivational deficits and a loss of interest or willingness to engage in usually pleasurable activities, including work and play.

These motivational deficits are reflected as anhedonia, a core (and likely the most disabling) symptom of depression, as well as other psychiatric disorders.

The paper also outlined how these effects of inflammation on the brain are an adaptation to the energy demands of inflammation that require conservation of energy resources, and thus the shutting down of behavior. Low-grade inflammation can be caused by lifestyle changes such as poor diet and sedentary behavior.

A vicious cycle can occur where poor lifestyle habits lead to increased inflammation that then reduce the person’s wherewithal or motivation to change those habits, says Andrew H. Miller, William P. Timmie professor of psychiatry and behavioral sciences. Miller and colleagues raise the possibility of developing treatments specifically for the motivational deficits caused by inflammation, moving to a more targeted approach to therapeutic development in psychiatry, resembling practices in oncology.

Miller co-authored the paper with colleagues in the Department of Psychology and the Emory Behavioral Immunology Program, including Michael J. Lucido, Mandy Bekhbat, David R. Goldsmith, Michael T. Treadway, Ebrahim Haroon and Jennifer C. Felger. 

 

A push for folic acid fortification in food to prevent spina bifida

A recent paper published in the American Journal of Epidemiology presented the need for a paradigm shift in evidence evaluation in policy-making for food fortification with folic acid for the prevention of spina bifida and anencephaly, two major neural tube defects affecting pregnancies worldwide.

Emory faculty Helena Pachón, Vijaya Kancherla and Godfrey P. Oakley, Jr. were co-authors on the article. The paper was a collaborative effort between the global health and epidemiology departments of Rollins School of Public Health, the Food Fortification Initiative and Nutrition International. More information here.

 

Promising results for head and neck cancer patients

Researchers at Winship Cancer Institute of Emory University played a leading role in two new studies that could change the way oncologists treat oral cavity squamous cell carcinoma (OCSCC), the most common form of head and neck cancer.

Pre-surgery immunotherapy may be safe and effective in treating some patients with OCSCC, according to the findings. The results (two papers) were published in Cell Reports Medicine, coming from a collaboration between Winship, MUSC Hollings Cancer Center and UCLA Jonsson Comprehensive Cancer Center.

Researchers tested the efficacy of treating patients prior to surgery with the immune checkpoint inhibitor anti-PD-1, which has transformed the way patients with advanced malignancies are treated. In the process, they identified potential molecular biomarkers in the blood and tumors of patients that show how likely they would be to respond to immunotherapy.

Chrystal Paulos, an associate professor in the Department of Surgery and Department of Microbiology and Immunology at Emory School of Medicine, led the research studies at Winship. Hannah Knochelmann, a graduate student in Paulos’ lab, is first author on one of the papers and second author on the other.

 

Veliparib of no benefit for advanced squamous lung cancer 

Winship Cancer Institute executive director Suresh Ramalingam was lead author on a multicenter study (970 patients) evaluating veliparib when added to platinum-based chemotherapy for advanced squamous cell lung cancer.

The study was published in the Journal of Clinical Oncology. Overall, there was no therapeutic benefit of adding veliparib to first-line chemotherapy for patients with advanced squamous cell lung cancer. However, a gene expression signature (called LP52) may identify a subgroup of patients likely to derive benefit from the PARP inhibitor veliparib with chemotherapy.

 

Race and ethnicity of children in clinical trials not representative of U.S.

An analysis of U.S. pediatric clinical trials found Black children were enrolled at a proportionally higher rate than their representation in the U.S. population, while other populations were under-represented.

Chris A. Rees, pediatric emergency medicine physician at Children’s Healthcare of Atlanta and assistant professor of pediatrics and emergency medicine at Emory University, conducted the study along with researchers from Boston Children’s Hospital. The study abstract, “Race and Ethnicity in Published Pediatric Clinical Trial Enrollment in the United States, 2011-2020,” was presented during the American Academy of Pediatrics 2021 National Conference.

The cross-sectional study reviewed 612 articles published in five leading general pediatric and five leading general medical journals from Jan. 1, 2011-Dec. 31, 2020. Researchers determined the reporting of participant race and ethnicity in published clinical trial results, comparing the number of children enrolled with U.S. Census populations of pediatric racial and ethnic groups.

Black children were enrolled in higher proportions than their representation in the U.S. Hispanic and Latino children were enrolled commensurate with their population; American Indian, Alaska Native, Asian and Native American-Pacific Islander children were enrolled significantly less relative to their population. White children were enrolled less than expected based on their representation in the U.S. population, but made up 46% of participants in trials reporting race or ethnicity.

More research is needed to determine the cause of these differences, but authors hypothesize they may be due to the locations where pediatric clinical trials are performed, the types of diseases and conditions that are studied, or may represent disparities in the trial enrollment process. Researchers also observed that a substantial number of trials did not report participant race or ethnicity at all.

 

Comparison of prostate surgery procedures and impact on quality of life

Martin Sanda, chair of Emory School of Medicine’s Department of Urology, was lead author of a multicenter prospective comparison of prostate surgery approaches — open versus robot-assisted radical prostatectomy — published in Journal of Urology.

The two groups studied (totaling almost 1,100 patients) had surgery between 2003 and 2013. They experienced similar long-range health-related quality of life outcomes, but there were advantages for the robot-assisted procedures. The study concluded that patients who underwent robot-assisted procedures had less pain, shorter hospital stays and fewer postsurgical complications such as blood transfusions, infections, deep venous thromboses and bladder neck contractures.

 

Potential signature of success for an HIV vaccine

Efforts to produce a vaccine against HIV/AIDS have been sustained for more than a decade by a single, modest success: the RV144 clinical trial in Thailand, whose results were reported in 2009. Now Emory, Harvard and Case Western Reserve scientists have identified a gene activity signature that may explain why the vaccine regimen in the RV144 study was protective in some individuals, while other HIV vaccine studies were not successful.

The researchers think this signature could be used to design future vaccines that will have a better chance of providing protection against HIV infection. The signature was observed in immune cells in the blood after vaccination and is based on targets for the transcription factor CREB1. The results, published in Nature Immunology, also contain hints on a contributing factor explaining why a recent HIV vaccine study conducted in South Africa (HVTN702) did not show a protective effect.

Lead author Rafick-Pierre Sekaly said it may not be necessary to take “shots in the dark” when testing vaccine platforms or adjuvants for efficacy. Instead, a focus could be identifying adjuvants and/or vaccine regimens that more potently induce the activation of the CREB1 signature. Sekaly is professor of pathology and laboratory medicine at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar. More information here.

 

Researchers evaluate how vaccine hesitancy changes over time

Researchers from Rollins School of Public Health recently published a paper in JAMA that explored how individuals overcome vaccine hesitancy, a major concern in the continuing COVID-19 pandemic.

First author Aaron Siegler, along with Travis Sanchez, Benjamin Lopman and Patrick Sullivan, found that more than one-third of vaccine-hesitant persons at baseline received a COVID-19 vaccine at follow-up three months later.

Therefore, the researchers said that policy makers and health care workers must not look at vaccine hesitancy as a stable trait that people have, but rather as a stance that changes over time. Public health efforts need to focus on this and capitalize on the willingness to be vaccinated when people are ready, the authors suggest.

 

Rapid and inexpensive assessment of soil iron content

Emory environmental scientist Debjani Sihi and co-authors developed an inexpensive technique to determine soil iron content using Nix Pro color sensor, a commercially available device costing less than $100.

They demonstrated that the Nix Pro color sensor can be widely used by farmers and extension scientists to estimate soil iron content, an essential element for plant growth. This rapid and inexpensive sensor method can help users understand the spatial distribution of soil iron with spatial autocorrelation between sampling locations in a field. 

The article was published in the journal Agricultural & Environmental Letters. This research was supported in part by the University Research Committee of Emory University and Emory College of Arts and Sciences. 

 

Corporate social responsibility’s relationship with investor trust

Suhas A. Sridharan from Emory’s Goizueta Business School was a co-author on a publication investigating whether a firm's corporate social responsibility (CSR) activities engendered investor trust.

The study was based on the observation that investor trust should facilitate greater informational price efficiency. The authors found evidence that CSR enhances investor trust in firms, such that firms with more CSR enjoy faster incorporation of earnings news into stock prices, lower investor uncertainty around earnings announcements, and higher earnings response coefficients.

Co-authors included Jonathan Berkovitch from Luiss Guido Carli University, Doron Israeli from Arison School of Business and Atanu Rakshit from Nazarbayev University.

 

At-home testing for HIV increases access, breaks down diagnosis barriers

Emory researchers partnered with the Centers for Disease Control and Prevention on a study evaluating the use of at-home tests for HIV, which increased access to testing for individuals who were unable to seek clinic or community-based testing. The results of the study were outlined in Morbidity and Mortality Weekly Report.

The program, called TakeMeHome.org, found that most participants in the program reported that they had either never tested for HIV (36%) or that they had last tested more than a year ago before receiving their self-test kit (56%).

The multidisciplinary team included Patrick Sullivan and Travis Sanchez from Emory’s Rollins School of Public Health. Collaborators include Elizabeth DiNenno and Kevin Delaney from the CDC and Natalie Cramer from National Alliance of State and Territorial AIDS Directors.

 

Timing of HCV drugs around liver transplant examined

Emory liver transplant surgeons Michael Turgeon and Shishir Maithel led a multicenter study examining the timing of direct-acting antiviral drugs for patients with hepatitis C-associated liver cancer, published in Annals of Surgery.

Given significant practice pattern variability and controversial literature linking direct-acting antiviral medications with an increased risk for liver cancer, the investigators sought to determine the most effective time to administer antiviral drugs. Turgeon and Maithel determined that the scheduling of therapy was important, observing that the ideal window to offer DAA therapy appeared to be in the early post-operative period (0-3 months) rather than before transplantation, due to improved rates of sustained virologic response and liver cancer recurrence-free survival.

The investigators also suggest that administration of antiviral drugs more than three months after transplant should be avoided, because regulatory T cell impairment induced by the drugs could combine with post-transplant immunosuppression and prolonged exposure to hepatitis C virus to create an increased risk of cancer recurrence. Additionally, recent data has described decreased cytotoxic function of natural killer cells and increased frequencies of myeloid-derived suppressor cells after antiviral therapy, which could contribute to an immunologic milieu where the hazard of liver cancer recurrence would be heightened. A prospective randomized, controlled trial is warranted to validate the results.

 

Testing models for psychopathology at the genomic level

In recent years, genome-wide association studies (GWAS) have provided insights into the genetic underpinnings of major psychiatric disorders, while various models have been proposed for the classification of such disorders. Accurate classification is a prerequisite for understanding the genetic and environmental links and for estimating an individual’s risk for developing one or more disorders.

World Psychiatry published research testing alternative structural models at the genomic level, led by Irwin Waldman, Emory professor of psychology. Co-authors included graduate student Holly Poore, former Emory postdoctoral fellow Justin Lunginham (now at the University of North Texas Health Sciences Center) and Jingjing Yang, assistant professor of human genetics at Emory University School of Medicine.

The researchers tested eight competing models for the classification of psychiatric disorders and related traits using summary statistics from 14 large GWAS studies of different disorders and traits (which reduced susceptibility to various biases and allowed the researchers to study psychopathology that occurs across the lifespan).

The best-fitting model comprised four correlated higher-order dimensions of psychopathology: externalizing (antisocial behavior and substance-use disorders), internalizing (depression and anxiety disorders), thought problems (schizophrenia and bipolar disorder) and neurodevelopmental disorders (attention deficit hyperactivity disorder and autism spectrum disorder). The four dimensions had distinct patterns of genetic correlations with a variety of demographic and personality traits such as educational attainment and neuroticism levels.

The researchers will build on this work by conducting a multivariate GWAS of the four dimensions to find their common and unique underlying genetic variants, genes and biological pathways.