Research roundup: Recent grants and publications for Emory faculty and staff
Jan. 25, 2021
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.
- Fixing Humpty Dumpty in cancer cells
Emory University will be part of a $5 million grant from The Andrew W. Mellon Foundation awarded to the University of Michigan’s Center for Social Solutions, led by former Emory Provost Earl Lewis, as part of the Foundation’s Just Futures initiative. “Crafting Democratic Futures: Situating Colleges and Universities in Community-based Reparations Solutions” emerges from the Center for Social Solutions’ focus on slavery and its aftermath, and is informed by three generations of humanistic scholarship and what that scholarship suggests for all seeking just futures. More information here.
The team of scholars will be led by historian Carol Anderson, Emory’s Charles Howard Candler Professor of African American Studies and department chair. The team also includes Emory College faculty members Vanessa Siddle Walker, Samuel Candler Dobbs Professor of African American Studies, and AAS assistant professors Janeria Easley and Jessica Stewart, with support from Department of History doctoral students Camille Goldmon and Aleo Pugh.
The project, which will span three years, creates and leverages a national network of scholars working in partnership with community-based organizations to develop research-informed reparation plans for each location. Other partners include Spelman College; Carnegie Mellon University; Rutgers University-Newark; Concordia College in Minnesota; Connecticut College; Wesleyan College in Macon, Georgia; Wofford College in Spartanburg, South Carolina; and the Council of Independent Colleges.
Lilly Endowment Inc. supports Candler theological education program
Candler School of Theology has received a grant of almost $1 million from Lilly Endowment Inc. to establish an initiative to support congregations in implementing new approaches to theological exploration, community engagement and collaborative leadership. The project will be situated within The Candler Foundry, Candler’s public theological education arm, led by Ryan Bonfiglio, assistant professor in the practice of Old Testament.
The grant is part of Lilly Endowment’s Thriving Congregations Initiative, a program providing $93 million in grants to 92 organizations who will work directly with congregations to help them gain clarity about their values and missions, explore and better understand the communities in which they serve, and draw upon their theological traditions as they adapt ministries to meet changing needs.
Candler’s Thriving Congregations grant will enable the school to further develop partnerships with churches in and beyond Atlanta in order to foster congregational vitality and address the cultural trends that challenge it. The grant will support and expand Courses in the Community and TheoEd Talks, two existing programmatic offerings from The Candler Foundry, which will culminate in Leadership Collaboratives, a new undertaking that aims to convene networks of congregational leaders to exchange ideas about ministry innovations and challenges. More here.
Two research teams from Winship Cancer Institute of Emory University were awarded pilot grants from the Donaldson Charitable Trust Research Synergy Fund, a funding mechanism offered jointly by Winship, the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. Each one-year grant of $125,000 is funded in part by contributions from the Oliver S. and Jennie R. Donaldson Charitable Trust.
The recipients for 2021 are Sarwish Rafiq and Erik Dreaden for "Improving CAR-T cell efficacy through optimal manufacturing with nanoparticle backpacks" and Deborah DeRyckere and Nicki Panoskaltsis for “MERTK and MEK inhibitor combination therapy for AML.” More here.
Emory Brain Health Center is announcing a new partnership with Genuity Science, a U.S.-headquartered data, analytics and insights organization, to help accelerate understanding of major neurodegenerative diseases.
Allan Levey, chair of the Department of Neurology at Emory University School of Medicine and director of the Goizueta Alzheimer’s Disease Research Center, says the partnership will accelerate drug discovery and clinical trials for conditions such as Alzheimer’s and Parkinson’s.
Genuity’s strategy is to combine detailed clinical and longitudinal data from large-scale, powered cohorts of many thousands of patients with whole genome sequences to provide discoveries beyond the usual suspects of disease genes. The collaboration will focus on the development of the Genuity population database with an initial focus on neurodegenerative disease, to enable research with pharma and biotech. More here.
Emory researchers have identified a way to put Humpty Dumpty back together again in cancer cells. That is, they’ve found a potential drug that corrects a defective protein-protein interaction in the tumor suppressor SMAD4, which is responsible for acceleration of colorectal and pancreatic cancer.
Scientists are very good at finding inhibitors for enzymes that are overactive. But they have meager results in terms of strengthening interactions that are weak or absent. An entire class of cancer-related genes is known as tumor suppressors, because they slow down cell division, repair DNA mistakes or tell cells to die when they are damaged. The new paper opens the door for similar studies on other tumor suppressors.
The results were reported Dec. 15 in Cell Chemical Biology. Senior author Haian Fu is chair of Emory’s Pharmacology and Chemical Biology department and leader of Winship Cancer Institute’s Discovery and Developmental Therapeutics program. Fu calls the approach “mutation-directed molecular glue.” More here.
Polystyrene is a polymer that occurs as a glassy solid at room temperature, but turns into a flowing, rubbery state when heated above about 100 degrees centigrade — its glass-transition temperature. Polymer materials are often made of blends of glassy and rubbery polymers to improve the toughness of the material. They are important for a variety of industrial and commercial uses. And yet, the mechanism behind how rubber toughening occurs at the molecular level near glassy-rubbery polymer interfaces is still unknown.
Now Yannic Gagnon, an Emory PhD candidate in physics, and Connie Roth, associate professor of physics, have shown that the temperature at which a material locally transitions from an equilibrium liquid to a non-equilibrium solid glass is strongly impacted by properties of the neighboring polymer at this interface.
ACS Macro Letters published the research, which used a fluorescence method to measure the local glass transition temperature at the polymer interface between glassy polystyrene and rubbery polydimethylsiloxane. The researchers found that varying the modulus of the rubbery material affected the local glass transition temperature at a distance of 50 nanometers away from the interface.
The results defy current theoretical efforts in the field to understand how local properties are changed near polymer interfaces. The Roth lab is continuing to map how local glass transition dynamics are coupled across polymer-polymer interfaces.
Biomedical engineer Hanjoong Jo’s lab has combined its elegant animal model of atherosclerosis with techniques that permit scientists to see molecular changes in single cells. The results were published Dec. 15 in Cell Reports.
The Jo lab’s model involves restricting blood flow in the carotid artery of mice, which are fed a high-fat diet and also have mutations in a gene (ApoE) involved in processing fat and cholesterol. The physical intervention causes atherosclerosis to appear within a couple weeks. Inflammation in endothelial cells, which line blood vessels, is visible within 48 hours.
With the single cell analysis, researchers in Jo’s lab saw that under disturbed flow conditions, endothelial cells begin to display surprising changes in their gene activity. It was not only that endothelial cells were becoming more pro-inflammatory, they looked like they were changing into immune cells. There were also signs of some endothelial cells de-differentiating – becoming more like mesenchymal (stromal) or progenitor cells.
The first author of the paper was postdoctoral fellow Aitor Andueza Lizarraga, with contributions from assistant professor Sandeep Kumar. More here.
A trend in oncology is to organize clinical trials by looking for cancer-driving mutations that are vulnerable to targeted therapies, rather than classifying tumors by anatomical origin. Winship investigator Kevin Kalinsky was lead author reporting on one of these trials, part of the National Cancer Institute’s NCI-MATCH study (Molecular Analysis for Therapy Choice), in JAMA Oncology. Kalinsky is director of the Glenn Family Breast Center at Winship Cancer Institute.
The study looked at the AKT inhibitor capivasertib’s efficacy against mostly breast and gynecologic cancers from 35 patients. Their cancers had all progressed to metastasis after standard treatments and their tumors all had a specific mutation in the AKT1 gene. The overall response rate was clinically significant at 28.6 percent, with one patient with endometrial cancer achieving a complete response and remaining on therapy for three years.
Winship Cancer Institute investigators examined the clinical and biological significance of four newly described subtypes of small cell lung cancer (SCLC), which accounts for 10-15% of lung cancers; it is more aggressive than the non-small cell form.
Analyzing tumor samples from SCLC patients, the researchers found that one of the subtypes (SCLC-Y) was associated with both higher YAP1 expression and more inflammation-related genes. These differences could inform prognoses and treatment decisions, especially with regards to the benefit of immunotherapeutic agents.
The findings were published on Nov. 25 in the Journal of Thoracic Oncology. The first author was Taofeek Owonikoko, professor of hematology and medical oncology and co-leader of Winship Cancer Institute’s Discovery and Developmental Therapeutics Program. The senior author was Gabriel Sica, associate professor of pathology and laboratory medicine.
Frontiers in Pharmacology published the first comprehensive review of plants with antibacterial activities, conducted by Emory scientists. Using rigorous selection data, the review surveyed more than 6,000 articles published within the past eight years and identified 958 plant species that show antibacterial activity and zeroed in on the 70 most promising plant species from the 15 families most studied in the literature.
The result depicts the current state of knowledge regarding antibacterials from plants and provides powerful recommendations for future research directions. The authors hope that the review will help guide potential new strategies to combat antimicrobial resistance, a serious threat to human health across the globe.
Senior author of the study is Cassandra Quave, associate professor in Emory’s Center for the Study of Human Health and the School of Medicine’s Department of Dermatology. First authors are Francois Chassagne, a post-doctoral fellow in the Quave lab, and Tharanga Samarakoon, collections manager of the Emory Herbarium. Co-authors include post-doctoral fellow Gina Porras; undergraduates Sarah Shabih and Darya Raschid Farrokhi; graduate students Akram Salam and Lewis Marquez; and staff scientists James Lyles and Micah Dettweiler.
Two recently published studies, one in the journal PLOS ONE and the other in Medicine, looked at blood markers and their association with outcomes in hospitalized COVID-19 patients. The research was a result of an interdisciplinary COVID-19 research team that met weekly beginning in Spring 2020, using real-time data from COVID-19 patients and front-line clinician experiences to guide ongoing treatment protocols at Emory. Together, their work provided valuable knowledge to understand which COVID-19 patients were at risk for clotting disorders and which patients were at risk for clinical worsening, so that adjustments in treatment could be made.
Investigators included researchers from the Departments of Medicine’s Division of Pulmonary, Allergy, Critical Care and Sleep Medicine as well as Neurology, Anesthesiology, and Hematology and Medical Oncology. Neurologists Srikant Rangaraju and Fadi Nahab’s study investigated D-dimer protein levels among COVID-19 patients. They found that both magnitude and rate of rise in D-dimer within the first 10 days of hospitalization are predictive for VTE (venous thromboembolic events) but not mortality.
Anesthesiologists Milad Sharifpour and Craig Jabaley’s work focused on levels of C-reactive protein (CRP) in a cohort of 268 adult patients, finding that CRP levels increased in a linear fashion during the first week of hospitalization and peaked on day five. Compared to patients who died, those who survived had lower peak CRP levels, and the levels were significantly higher in patients who died compared to those who survived.
The hydrogen bond is central to chemistry and biochemistry. Chemists from Emory University and the University of Chicago discovered that an usually strong variety of a hydrogen bond also shares characteristics with a covalent bond, and is actually a hybrid of both. Science published the finding, which shows that chemical bonding can occur on a continuum, rather than as a pure hydrogen bond or a pure covalent bond, as traditionally thought.
Adrei Tokmakoff and Bogdan Dereka from the University of Chicago wanted to understand why some hydrogen bonds are stronger than others. They used spectroscopy to study hydrogen bonds in a range of lengths and strengths in a simple system of hydrogen and fluorine in an aqueous solution. They found that a shorter hydrogen bond indicated stronger hydrogen bonding and a relatively weaker covalent bond. At a certain point, however, this trend reversed. Even as the hydrogen bond became shorter, the hydrogen was shared equally between two fluorines, meeting the description of a covalent bond.
Emory theoretical chemist Joel Bowman and former Emory graduate student Qi Yu performed high-level quantum computer simulations to understand the behavior and more precisely characterize when the shift from conventional hydrogen bond to a covalent bond occurs along the continuum. Yu is now a postdoctoral fellow at Yale University. Additional co-authors are Nicholas Lewis and William Carpenter from the University of Chicago.
Before the COVID-19 pandemic, concern among infectious disease specialists was rising about Candida auris, an emerging fungal pathogen that is often drug-resistant and difficult to eradicate from hospitals.
Emory Antibiotic Resistance Center director David Weiss and colleagues have identified a combination of existing antifungal drugs (micafungin and amphotericin B) with enhanced activity against C. auris when used together. The results were published in a letter to The Lancet Microbe. Postdoctoral fellow Siddharth Jaggavarapu was the first author.