Research roundup: Recent grants and publications for Emory faculty and staff
Dec. 15, 2020
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.
Basic and translational research
- Capturing roaming molecular fragments in real-time
- Marine natural products may hold potential for human medicine
- Don’t go slippery on me, tRNA
- Unusual partnership may drive neurodegeneration in Alzheimer’s
- Hsp90 inhibitor may enhance immunotherapy for pancreatic cancer
- Pediatric risk index for blood-forming cell transplants
- Another side to cancer immunotherapy?
Environmental, life science and public health research
- Prevalence of diabetes increasing in India and Pakistan
- Worldwide flour fortification standards need update
- Bedaquiline as a milestone in tuberculosis treatment
- Rural-urban differences in obesity and diet quality
- Coastal storm surges likely to grow more severe, study shows
Sergio Delgado Moya, associate professor of Spanish and Portuguese, has been awarded one of the Andy Warhol Foundation’s Arts Writer Grants.
Projects supported by the program address both general and specialized art audiences, from scholarly studies to critical reviews and magazine features. Moya will receive $50,000 to complete his book “An Archive of Violence: The Obscene Visuality of Sensationalism.” The book makes a case for sensationalism as a specific kind of violence that falls on marginalized populations who are marked by gender and class, by race and ethnicity, by dispossession and by sexuality.
Prethy Rao, assistant professor in the Vitreoretinal Surgery and Diseases section of Emory Eye Center, was the recipient of a $35,000 Research to Prevent Blindness/American Academy of Ophthalmology Award for IRIS® Registry Research.
Rao will use the IRIS Registry to evaluate the timing and rate at which children require cataract surgery following vitrectomy, a procedure that is part of treating several eye conditions. This real-world evidence will help ophthalmologists counsel patients and their families regarding future complications.
Rao’s primary research interests include “big data” analysis to better understand risk factors and clinical outcomes of several adult and pediatric vitreoretinal diseases to aid in widespread clinical practice patterns.
Basic and translational research
An international research team observed a chemical reaction at the atomic level in real time. Science published the observation — long a major goal of chemical physics. The unusual “roaming” reaction pathway was first reported in 2004 by two of the current paper’s co-authors: Joel Bowman, Emory professor of theoretical chemistry, and Arthur Suits, of the University of Missouri. The roaming pathway was seen in theoretical simulations by Bowman’s group, but only inferred in an experiment.
In the latest work, this pathway was directly observed using a femtosecond Coulomb explosion imaging apparatus at the Institut National de la Recherche Scientifique (INRS) in Quebec. Bowman, former Emory graduate student Chen Qu, Paul Houston (Cornell and Georgia Tech), Tomoyuki Endo (INRS), Simon Neville and Michael Schuurman (the Canadian National Research Council) comprised the theoretical team that simulated the pioneering experiments and provided crucial agreement with them.
Heide Ibrahim of the INRS conceived of the experiment and led the current work with the support of Francois Legare, also from the INRS.
Watch a video about the discovery.
A review by Emory chemists highlights marine natural products from across the Caribbean region that possess antiproliferative, anti-inflammatory and antipathogenic properties, as well as efforts to synthesize bioactive analogs for them. Bioorganic and Medicinal Chemistry published the review, led by Adrian Demeritte, a graduate student from the Bahamas. Demeritte is a member of the lab of Bill Wuest, associate professor in the Department of Chemistry, and co-author of the review.
The authors note a steady increase in the number of new compounds isolated from marine natural products in recent years, including small molecules that may hold potential for pharmaceutical development. Many marine natural products are derived from various species of gorgonians, tunicates, algae, mollusks and sponges, all of which thrive in the Caribbean — one of the world’s greatest centers of endemic biodiversity and the cradle of marine natural product research.
The review, titled “A look around the West Indies: The spices of life are secondary metabolites,” urges more funding for the potential of marine natural products and for countries of the Caribbean to promote research facilities geared toward natural product isolation and encourage the study of the practice in local universities.
RNA can both carry genetic information and catalyze chemical reactions, but it’s too wobbly to accurately read the genetic code by itself. Enzymatic modifications of transfer RNAs – the adaptors that implement the genetic code by connecting messenger RNA to protein – are important to stiffen and constrain their interactions.
Emory biochemist Christine Dunham’s lab published a paper in eLife showing how a modification on a proline tRNA prevents the tRNA and mRNA from slipping out of frame. The basics of these interactions were laid out in the 1980s, but the Dunham lab’s structures provided a comprehensive picture with mechanistic insights.
The X-ray crystal structures indicate that tRNA methylation – a relatively small bump — at position 37 influences interactions between the tRNA and the ribosome. The first author of the eLife paper was former Emory graduate student and postdoc Eric Hoffer, who is now working for Johnson & Johnson. More here.
Emory researchers have gained insights into how toxic Tau proteins kill brain cells in Alzheimer’s disease and other neurodegenerative diseases. The results were published in PNAS.
Tau is the main ingredient of neurofibrillary tangles, one of two major hallmarks of Alzheimer’s. Pathological forms of Tau appear to soak up and sequester a regulatory protein called LSD1, preventing it from performing its functions in the cell nucleus. In mice that overproduce a disease-causing form of Tau, giving them extra LSD1 slows down the process of brain cell death.
Senior author David Katz, associate professor of cell biology, says that inhibition of LSD1 may be a critical mediator of neurodegeneration caused by pathological Tau, and blocking the interaction between pathological Tau and LSD1 could be a potential therapeutic strategy for Alzheimer’s and other diseases.
While the Katz lab’s research was performed in mice, they have indications that their work is applicable to human disease. They’ve already observed that LSD1 abnormally accumulates in neurofibrillary tangles in brain tissue samples from Alzheimer’s patients.
Inhibition of Hsp90 could enhance sensitivity to immunotherapy agents in pancreatic cancer, according to research from Greg Lesinski’s laboratory at Winship Cancer Institute of Emory University. Pancreatic cancer has been relatively resistant to immunotherapy approaches that have transformed the treatment of other types of cancer.
In a paper in Molecular Cancer Therapeutics, Lesinski’s lab showed that the Hsp90 inhibitor XL888 could inhibit the growth of pancreatic stellate cells, which form dense “nests” around tumor cells and inhibit immune system access. Hsp90 is a heat shock protein that acts as “chaperone” (protein folding assistant) to several inflammatory regulators.
XL888 also enhanced the activity of checkpoint inhibitors against pancreatic cancers in mice, increasing the ability of immune cells to infiltrate the tumors. The first author of the paper was visiting medical student Yuchen Zhang. A related clinical trial is ongoing at Winship, under the direction of Bassel El-Rayes.
A disease risk index developed for adults undergoing blood-forming cell transplants has been validated in children and adolescents, in an international study led by pediatric hematologist-oncologist Muna Qayed. The results were published in the journal Blood.
The study included more than 2,500 children and adolescents with acute myeloid or lymphoblastic leukemia undergoing hematopoetic cell transplantation. The risk index, which can be used to stratify and facilitate prognosis, takes into account age, the patient’s disease status and the genetic characteristics of their cancer cells.
Qayed is associate professor in the Department of Pediatrics and medical director of the Cellular Therapy Laboratory at Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta.
Immunotherapies have transformed the treatment of several types of cancer over the last decade. Yet they focus on reactivating one arm of the immune system: cytotoxic T cells, which sniff out and kill tumor cells.
In a paper in Nature, scientists at Emory Vaccine Center and Winship Cancer Institute of Emory University (Winship) reported on their detailed look at B cells’ presence inside tumors. B cells represent the other major arm of the adaptive immune system, besides T cells, and could offer opportunities for new treatments against some kinds of cancers.
Emory investigators Andreas Wieland, Rafi Ahmed and colleagues decided to concentrate on head and neck cancers that were positive for human papillomavirus (HPV). The virus provides a defined set of tumor-associated antigens, facilitating the study of tumor-specific B cells across patients.
The researchers worked with Winship oncologist Nabil Saba and surgeon Mihir Patel to obtain samples of head and neck tumors removed from 43 patients.
Within HPV-positive tumors, researchers found an enrichment for B cells specific to HPV proteins; a subset of these cells were actively secreting HPV-specific antibodies. In the tumors, they could see germinal center-like structures, resembling the regions within lymph nodes where B cells are “trained” during an immune response. More here.
Environmental, life science and public health research
The prevalence of diabetes in three major cities in India and Pakistan increased over five years, with nearly one in five adults affected by the condition, according to a study published in Diabetic Medicine. During the same period, there was inconsistent progress on improving cardiovascular health indicators.
Mohammed K. Ali, associate professor of global health and epidemiology at the Rollins School of Public Health, was a senior author of the study and notes that the findings emphasize the need for more comprehensive approaches to manage diabetes. The study was coordinated by the India-based Center of Excellence in Cardio-metabolic Risk Reduction in Southeast Asia (CoE-CARRS), a collaboration between Emory University and several partner institutions in the region.
The study looked at changes in the prevalence of diabetes and the quality of diabetes care from 2010/2011 to 2015/2016. Investigators found that while the prevalence of diabetes in Delhi, Chennai and Karachi increased by one percent, only 7% of patients met all four treatment goals for diabetes. There was also little change among individuals for two important parameters to manage diabetes and overall heart health: smoking and blood pressure control. More here.
Half of the countries that fortify maize and wheat flours with iron, zinc and vitamin B12 may need to update their standards to meet the World Health Organization’s (WHO) current recommendations, according to a recent study published in Food Policy.
For decades, many countries have recommended or required that the food industry produce "fortified" foods by adding a small amount of vitamins and minerals (micronutrients) into basic food staples and condiments that almost all consumers can afford. Food is fortified to prevent micronutrient deficiencies that can boost a child’s academic achievement, increase adult productivity and prevent disabling or fatal birth defects.
First author Katya Bobrek completed the work as an undergraduate student in Anthropology and Human Biology at Emory under the supervision of Helena Pachon, research professor at the Rollins School of Public Health and senior nutrition scientist for the Food Fortification Initiative. More here.
Rollins School of Public Health faculty members Kenneth G. Castro and Sarita Shah were guest editors on a special supplement to The International Journal of Tuberculosis and Lung Disease. The supplement features 10 peer-reviewed reports describing global experiences regarding bedaquiline use as a treatment for drug-resistant tuberculosis (TB) in diverse country settings.
Bedaquiline was approved in late 2012 by the U.S. Food and Drug Administration (FDA) and is the first anti-TB drug approved by the FDA in more than 40 years — a gigantic milestone in TB management and care. With the advent of bedaquiline, practitioners are able to move away from injectable treatments needed for 18-24 months, making the administration of TB drugs easier.
Despite this positive step, Castro stresses the need for continued research and development to identify and make readily available shorter treatment regimens for people with drug-resistant TB. “We cannot become complacent,” he says.
Though it is both preventable and treatable, TB remains one of the top 10 causes of death worldwide, and is a disease that is prevalent in every country and across all age groups. On a global scale, 10 million new TB cases are identified every year. Of those, half a million of the cases will be in individuals with rifampicin or multidrug-resistant forms of TB. More here.
Using national survey data, Emory and Stanford investigators examined how residents from urban and rural areas navigate their food environments. The findings, published in the Journal of Rural Health, show that self‐reported rurality of residential area is associated with food acquisition behaviors and may explain rural‐urban differences in obesity and diet quality.
Respondents living in rural areas shopped for groceries less frequently, drove further, more commonly shopped at small grocery stores and supercenters, and used restaurants less frequently. In multivariable analyses, rural, small town and suburban areas were each significantly associated with BMI and fruit and vegetable intake, but not percent energy from fat.
The corresponding author was Michelle C. Kegler, director of the Emory Prevention Research Center and a Winship member, with senior author Ilana G. Raskind of the Stanford Prevention Research Center.
Coastal storm surges will likely become more severe in the United States by 2100, finds a study by a team of researchers including Talea Mayo, assistant professor in Emory’s Department of Mathematics. Frontiers in Built Environment published the research, which examined the relationships between storm surge inundation and storm characteristics to gain more insight into the impacts of climate change.
The researchers simulated the storm surges of 21 past hurricanes under future climate conditions to assess the changes that may be produced by hurricanes at the end of the century. The results show that on average, storm surge inundation volume and extent will both increase, with notable increases along the Gulf Coast, the Carolinas and New Jersey. The simulations found that inundation volume increased by 36% on average and the inundation extent increased by 25% on average.
The work provides a fundamental first step in coastal hazard assessment under climate change. First author of the study is Jeane Camelo, from the University of Central Florida who did the work as a graduate student of Mayo. Ethan Gutmann, from the National Center for Atmospheric Research, is a co-author.