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

March 10, 2022

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Research Roundup offers a sample of recent grants and publications for Emory faculty and staff. To suggest items for the next column, please email submissions to Research Roundup.

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).

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.

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

Jia receives NSF CAREER Award for live cell imaging

The National Science Foundation has bestowed biomedical engineer Shu Jia a Faculty Early Career Development (CAREER) Award, which will support his research program advancing microscope technology in biology. The five-year award totals more than $790,000.

Jia, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, is building a next-generation platform for fluorescence microscopes that could reshape how we see live cells, capturing ultrafast 3D images of single cells.

Jia aims to improve the resolution of conventional microscopes by amping up a technique called microfluidics imaging to achieve detailed and clear 3D images of cells in flow in one snapshot.

The idea is to simplify and speed up how researchers and doctors study cells while limiting cell damage from extended exposure to light during the imaging process. Read more about the work here.

Olson receives NCI grant to study integrin antagonists in medulloblastoma

The National Cancer Institute has awarded a two-year R21 grant of $183,000 to Jeffrey Olson, professor of neurosurgery and hematology and medical oncology, for his project, “Targeting Integrin Pathways by GLPG-0187 in Medulloblastoma.”

The study will investigate the potential of GLPG-0187, a broad-spectrum integrin receptor antagonist. Beta-1 integrins are overexpressed in medulloblastoma and preliminary results show that GLPG-0187 can inhibit medulloblastoma cell growth.

Candler faculty earn Louisville Institute research grants

Three Candler School of Theology faculty have received grants from the Louisville Institute to support their work. Professor of World Christianity Jehu J. Hanciles has been awarded a Project Grant for Researchers for his project “African Immigrants and Transformations in American Christianity.” His work studies how African immigrants and their adult children factor into the American church, bringing unique gifts and resources to major cultural shifts while navigating intergenerational issues around identity and religious commitment.

Susan B. Reynolds, assistant professor of Catholic Studies, also has been awarded a Project Grant for Researchers for “Ways of the Cross: Passion and Protest as Public Theology.” Drawing on fieldwork, interviews and archival research, Reynolds will examine protests staged by churches and other Christian communities in response to contemporary social concerns such as gun violence, structural racism and anti-Black violence, homophobia, injustice toward migrants and the COVID-19 pandemic.

In addition, Professor of Hebrew Bible Roger S. Nam received a Sabbatical Grant for Researchers to support his upcoming book “The Economics of Diaspora” (Oxford University Press). His work seeks to apply diasporic theory  to readings of three text clusters that represent different components of the Judean diaspora.

Publications

New system speeds screening of drug-delivering nanoparticles

An improved “DNA barcoding” system could streamline animal preclinical nanoparticle studies and speed up the development of RNA therapies.

In the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, James Dahlman, Phil Santangelo and collaborators have developed a technique called DNA barcoding. Scientists insert unique snippets of DNA into custom-made delivery vehicles: lipid nanoparticles, which are injected into mice. Genetic sequencing is then used to determine which barcodes have reached which specific targets.

A new system, described in Nature Nanotechnology, takes the screening process a step further. Previously, it was known that cellular factors affecting LNP delivery vary between pre-clinical species and humans but the extent of those differences was unknown. The team compared nanoparticle delivery simultaneously in mouse, primate and living human cells, all within specially engineered mice. Read more about their work here.

Using PI3 kinase inhibitors to enhance CART cell therapy

CART cell therapy is a promising form of cancer immunotherapy but is limited by immune exhaustion when used for chronic lymphocytic leukemia (CLL). The therapy could be enhanced with a class of drugs called PI3 kinase delta/gamma inhibitors, according to the findings of an Emory-led study published in Blood.

Exposure of CART cells to a PI3 kinase delta/gamma inhibitor (duvelisib) during the manufacturing enriched the cells for stem-like qualities and enhanced efficacy in eliminating CLL in animal models, the researchers found.

Lead authors of the study were resident Christopher Ronald Funk and postdoctoral fellow Shuhua Wang. The corresponding author was Edmund K. Waller, Rein Saral Professor in Cancer Medicine at Winship Cancer Institute and medical director of the Center for Stem Cell Processing and Apheresis at Emory University Hospital.

The research was supported by Verastem Oncology, maker of duvelisib, through a sponsored research agreement. In addition, the research was supported through a Howard Hughes Medical Institute fellowship, the National Cancer Institute (R01CA208328), the Leukemia and Lymphoma Society and the Georgia Clinical and Translational Science Alliance (National Center for Advancing Translational Sciences UL1TR000454).

Biomarker could facilitate detection of uveal melanoma metastases

Research from Emory Eye Center could open a new avenue for detecting early-stage metastatic uveal melanoma in the liver. The findings from Hans Grossniklaus’s group appeared in Cancer Gene Therapy.

Uveal melanoma is an ophthalmic cancer that almost exclusively metastasizes in the liver.

Researchers observed elevated levels of the chemokine receptor 4 (CXCR4) in liver metastases from uveal melanoma patients, and in liver metastases in mouse models of uveal melanoma.

A CXCR4-specific MRI imaging contrast agent, developed by co-author Jenny Yang at Georgia State University, enabled early detection of small liver metastases in multiple mouse models. The relative simplicity of this approach may eventually offer patients a valuable option for detection and treatment, Grossniklaus says.

Disturbed blood flow points toward potential CV therapeutic

It’s not a blockbuster cardiovascular drug — yet. But the pathway from bench to bedside is easy to see. In a recent eLife paper, Hanjoong Jo’s lab characterizes a “flow-kine”: a protein produced by endothelial cells in response to healthy blood flow patterns. Unlike other atherosclerosis-linked factors previously identified by Jo’s team, this one — called KLK10 — is secreted. That means the KLK10 protein could morph into a therapeutic.

Jo and his colleagues are in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. Using a workhorse model of disturbed blood flow in atherosclerosis, his team has steadily identified a stream of genes involved in the disease process. KLK10 is one of several down-regulated by disturbed blood flow.

KLK10 can be compared to PCSK9 inhibitors, which lower LDL cholesterol and have a proven ability to prevent cardiovascular events. KLK10 acts in a different way, not affecting cholesterol, but instead inhibiting inflammation in endothelial cells.

Accordingly, KLK10 can protect against atherosclerosis in animal models, when delivered by injection. Jo sees similarities between KLK10 and myokines, exercise-induced proteins secreted by skeletal muscle cells. Looking ahead, his lab has begun experiments testing how exercise affects KLK10 and other protective factors. Learn more here.

Proteomic analysis reveals new aspects of Alzheimer’s

Comprehensive analysis of the proteins in the brains of people with Alzheimer’s disease can reveal aspects of disease not reflected in RNA-based gene expression studies, according to Emory Brain Health Center research published in Nature Neuroscience.

Emory scientists analyzed brain tissue samples from more than 500 people with symptomatic and asymptomatic Alzheimer’s and controls. They identified a “module,” a group of closely related proteins, connected with the most common genetic risk factor for Alzheimer’s (APOe4). The team also identified a separate module associated with the rate of cognitive decline, independent of Alzheimer’s pathology. Targeting both modules could eventually form the basis of new Alzheimer’s therapies, the authors write.

Co-first authors were neurologist Erik Johnson, postdoctoral fellow E. Kathleen Carter and associate scientist Eric Dammer, with biochemist Nick Seyfried as senior author.

Ventricular-arterial uncoupling driving hypertension in college football players

American football players are at risk for early development of hypertension despite intense exercise. A maladaptive mechanism called ventricular-arterial uncoupling may explain the high rate of hypertension and impaired cardiac function among college football players, according to new research from Emory cardiologist Jonathan Kim and colleagues.

The results were published in the Journal of the American Heart Association.

Kim and colleagues from Emory and Harvard studied 200 football players from Georgia Tech and Furman University from 2016 to 2019. In this group, ventricular–arterial uncoupling was associated with increased systolic blood pressure and impaired left ventricular function, assessed through echocardiography.

Ventricular-arterial uncoupling reflects a mismatch between elasticity in the arteries and in the left ventricle of the heart, and may represent an important mechanism underlying adverse cardiovascular health and outcomes prevalent among retired professional American football players, the authors say.

The first author of the paper was cardiology fellow Jason Tso. Kim and Aaron L. Baggish of Harvard are team cardiologists for the Atlanta Falcons and New England Patriots, respectively.

HPV vaccination supported in young cancer survivors

The immunogenicity and safety of the human papillomavirus vaccine (HPV) three-dose series in survivors of cancer is similar to that in the general population, researchers led by professor of pediatrics at Winship Cancer Institute of Emory University and Children's Healthcare of Atlanta have found.

Their findings providing evidence supporting HPV vaccination in a population that has an increased risk for developing HPV-related cancers. A team led by Emory professor of pediatrics James Klosky and Wendy Landier of the University of Alabama at Birmingham conducted the study, enrolling 453 young cancer survivors (age 9-26) from five National Cancer Institute-designated comprehensive cancer centers.

Klosky and Landier are senior and lead author of the paper published in The Lancet: Child and Adolescent Health. Other authors included Karen Wasilewski-Masker, associate professor of pediatrics, and Brooke Cherven, assistant professor of pediatrics. Klosky and Landier received a grant from the National Cancer Institute to conduct the study.

Poop substitute is effective vs. C. diff

A pill derived from human feces can effectively ward off Clostridium difficile diarrhea, according to the results of a clinical trial published in the New England Journal of Medicine.

Clinical microbiologist/infectious disease specialist Colleen Kraft and Emory patients contributed to the Phase III, 182 patient study, which was sponsored by Seres Therapeutics. Kraft is associate chief medical officer at Emory University Hospital and 2022 president-elect of the American Society for Microbiology.

Seres’ pill is an alternative to fecal microbiota transplant (FMT), a treatment for C.difficile that has been difficult to standardize, because the microbial components in FMT material vary with the individual donor, diet and time. Moving toward an “off the shelf” product, Seres takes stool from prescreened donors and treats the material with ethanol, killing some microbes and leaving behind bacterial spores that can compete for intestinal real estate with C. difficile. Read more about the study.

Opioid antidote dosing study selected as Emergency Medicine board standard

The American Board of Emergency Medicine has selected a 2019 paper from Emory and Georgia Poison Center authors for its 2023 Medical Toxicology Lifelong Learning and Self-Assessment Reading List. Such articles are considered highly relevant to the subspecialty and represent the most important information that physicians need to keep up with. The paper is  “Naloxone Dosing After Opioid Overdose in the Era of Illicitly Manufactured Fentanyl,” from Department of Emergency Medicine vice chair Brent Morgan and colleagues.

Disparities, race influence survival rates in breast cancer

Among Black women with breast cancer, individual disparities in insurance and neighborhood socioeconomic measures correlated with overall survival, according to an analysis of data from a randomized clinical trial involving almost 10,000 people. Gelareh Sadigh, assistant professor of radiology and imaging sciences, was lead author of the study, published in JAMA Oncology.

Sadigh and colleagues analyzed data from the TAILORx (Trial Assigning Individualized Options for Treatment) study. Black women with early hormone receptor-positive breast cancer experienced reduced rates of overall survival compared with white women. Black compared with white race was associated with significantly shorter relapse-free intervals (hazard ratio 1.39) and overall survival (hazard ratio 1.49), adjusting for insurance and neighborhood deprivation level.

Learning about opioid withdrawal strategies through Reddit

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory’s Department of Biomedical Informatics recently published a paper in Clinical Toxicology focusing on the phenomenon of precipitated withdrawal, in collaboration with emergency medicine specialists from Penn, Rutgers and Mt. Sinai. The paper analyzes Reddit discussions on precipitated withdrawal and microdosing approaches to avoiding it.

Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment with buprenorphine. Precipitated withdrawal is reported to occur more often when someone has a history of fentanyl use, possibly because fentanyl remains in the body’s peripheral tissues, even during periods of abstinence. More information is here.

Tracking the first Omicron case detected in Georgia

The first Omicron case detected in Georgia through SARS-CoV-2 genomic surveillance probably became infected during a visit to Cape Town, South Africa, according to a recent case report in Clinical Infectious Diseases.

The lead authors of the case report were Marybeth Sexton, chief quality officer for the Emory Clinic, and infectious disease specialist Jesse Waggoner. The senior author was viral geneticist Anne Piantadosi.

The report demonstrates how current COVID-19 vaccines do not completely protect from Omicron. The patient was a woman in her 30s, who was fully vaccinated with Pfizer/BioNTech twice, then received a booster in October 2021 — about six weeks before becoming sick. She had a negative PCR test shortly before traveling back to Georgia but developed symptoms around the time of her return flight.

The woman was diagnosed with COVID-19 at the end of November, a few days after her return to Georgia — just after Omicron was declared a Variant of Concern by the WHO. This single case report is not representative of the overall severity of Omicron, which is generating a large number of infections, burdening hospitals in Georgia and elsewhere. The patient experienced muscle aches, nausea, fatigue and cough, but did not have a fever or shortness of breath and did not require hospitalization. Read more about the case here.

Exploring brain signals that underlie learning

An area of the brain traditionally thought to be a basic sensory signaling center — the primary somatosensory cortex — may play a deeper role in decision making, neuroscientists think. The primary somatosensory cortex appears to be part of an adaptive framework in the brain that facilitates flexible behavior as individuals gain experience.

In the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, members of Garrett Stanley’s lab studied neural signaling that correlates with adaptive behavior in mice. What they found, published in Nature Communications, could guide scientists toward new strategies to improve and speed up learning. Researchers made recordings of neurons in mice that were responding to whisker stimuli, being rewarded or adapting to shifting stimuli. Read about their work here.

New chemical approach to antiseptics may ease resistance

For nearly 100 years, commercial disinfectants have relied on quaternary ammonium compounds, also known as quats or QACs, for their active ingredients. While there has been little innovation around QACs, the bacteria and viruses they target are constantly evolving. Increased use of QACs during the COVID-19 pandemic highlights the problem of potentially boosting antimicrobial resistance to QACs.

Emory professor of chemistry William Wuest and colleagues have found that an alternative suite of chemicals may help combat the problem of resistance. The journal ACS Infectious Diseases published their finding that quaternary phosphonium compounds, or QPCs, appear to be more effective than QACs against a broad range of pathogens. Tests showed that QPCs could kill six strains of bacteria, including methicillin-resistant Staphylococcus aureus and Escherichia coli. Even after administering low doses of the chemicals over a month, the bacteria were not able to evade the lethal doses of QPC, a promising sign that QPCs hold potential as an alternative to QACs.

Co-first authors of the study are Emory graduate student Marina Michaud and Kyle Sommers, from Villanova University. Wuest is senior author of the study, along with Kevin Minbiole from Villanova.

Experience with partner refocuses brain response to “love hormone”

Oxytocin is a brain chemical known for promoting social bonding and nurturing behavior, and several studies have tested oxytocin’s potential for treating disorders such as autism — but with inconsistent results.

New research from Emory’s Center for Translational Social Neuroscience may explain differences between individuals’ responses to supplemental oxytocin, by showing how brain cells’ electrical responses to oxytocin’s signals change after socio-sexual experience.

Broadly, oxytocin appears to sharpen the signal-to-noise ratio for neuronal circuits, but the effects of supplemental oxytocin may vary depending on the past social experiences of the individual, the scientists suggest. The results were published Feb. 1 in Current Biology.

The study was conducted in female prairie voles, rodents that form lifelong bonds with their partners, in collaboration with Larry Young’s lab at Yerkes National Primate Research Center, Emory University. Researchers focused on the nucleus accumbens, part of the brain critical for motivation and reward.

Scientists likened the electrical responses of neurons to oxytocin signals to an analog television, before and after the television is tuned to a station. Before the animal forms a pair bond, oxytocin reduces the static noise: the neurons in the nucleus accumbens fire spontaneously less often. But after an animal has been exposed to a partner, it increases the clarity of the signal from the station: the neurons gradually fire with greater strength — but only when electrically triggered. Read more about the research here.

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