Donated blood from COVID-19 survivors could be an effective treatment in helping others fight the illness – and should be tested more broadly to see if it can “change the course of this pandemic,” two Emory pathologists say.
The idea of using a component of survivors’ donated blood, or “convalescent plasma,” is that antibodies from patients who have recovered can be used in other people to help them defend against coronavirus.
Emory pathologists John Roback, MD, Read more
Research from Adam Marcus’ and Mala Shanmugam’s labs was published Tuesday in Nature Communications – months after we wrote an article for Winship Cancer Institute’s magazine about it. So here it is again!
At your last visit to the dentist, you may have been given a mouth rinse with the antiseptic chlorhexidine. Available over the counter, chlorhexidine is also washed over the skin to prepare someone for surgery. Winship researchers are now looking at chlorhexidine Read more
Stimulating immune cells with two cancer immunotherapies together can shrink the size of the viral “reservoir” in SIV-infected nonhuman primates treated with antiviral drugs. Important implications for the quest to cure HIV, because reservoir shrinkage has not been achieved consistently Read more
In the autoimmune disease systemic lupus erythematosus or SLE, the immune system produces antibodies against parts of the body itself. How cells that produce those antibodies escape the normal “checks and balances” has been unclear, but recent research from Emory University School of Medicine provides information about a missing link.
Investigators led by Ignacio (Iñaki) Sanz, MD, studied blood samples from 90 people living with SLE, focusing on a particular type of B cells. These “DN2” B cells are relatively scarce in healthy people but substantially increased in people with SLE.
The results were published in the journal Immunity.
People with lupus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Levels of the DN2 cells were higher in people with more severe disease or kidney problems. DN2 B cells are thought to be “extra-follicular,” which means they are outside the B cell follicles, regions of the lymph nodes where B cells are activated in an immune response.
“Overall, our model is that a lot of lupus auto-antibodies come from a continuous churning out of new responses,” says postdoctoral fellow Scott Jenks, PhD, co-first author of the paper. “There is good evidence that DN2 cells are part of the early B cell activation pathway happening outside B cells’ normal homes in lymph nodes.”
Previous research at Emory has shown that African American women have significantly higher rates of lupus than white women. In the current study, the researchers observed that the frequency of DN2 cells was greater in African American patients. Participants in the study were recruited by Emory, University of Rochester and Johns Hopkins. Read more
A genetic disorder caused by silencing of a gene on the X chromosome, fragile X syndrome affects about one child in 5,000, and is more common and more severe in boys. It often causes mild to moderate intellectual disabilities as well as behavioral and learning challenges.
Amy Talboy, MD
The gene responsible for fragile X syndrome, the most common inherited form of intellectual disability, was identified more than 25 years ago. Emory genetics chair Stephen Warren played a major role in achieving that milestone. His work led to insights into the molecular details of learning and memory, and nationwide clinical trials — which have a more complicated story.
Treating the molecular basis of a neurodevelopmental disorder, instead of simply addressing symptoms, is a lofty goal – one that remains unfulfilled. Now a new study, supported by the National Institute of Neurological Disorders and Stroke, is reviving a pharmacological strategy that Warren had a hand in developing.
“This is a very well thought out approach to studying changes in language and learning in children who are difficult to test,” says Amy Talboy, medical director of Emory’s Down Syndrome and Fragile X clinics, who is an investigator in the NINDS study. “It could change how we conduct these types of studies in the future.” Read more
At a recent symposium of cellular therapies held by the Department of Pediatrics, we noticed something. Scientists do not have consistent language to talk about a type of cells called “mesenchymal stem cells” or “mesenchymal stromal cells.” Within the same symposium, some researchers used the first term, and others used the second.
Guest speaker Joanne Kurtzberg from Duke discussed the potential use of MSCs to treat autism spectrum disorder, cerebral palsy, and hypoxic-ischemic encephalopathy. Exciting stuff, although the outcomes of the clinical studies underway are still uncertain. In these studies, the mesenchymal stromal cells (the language Kurtzberg used) are derived from umbilical cord blood, not adult tissues.
Nomenclature matters, because a recent editorial in Nature calls for the term “stem cell” not to be used for mesenchymal (whatever) cells. They are often isolated from bone marrow or fat. MSCs are thought have the potential to become cells such as fibroblasts, cartilage, bone and fat. But most of their therapeutic effects appear to come from the growth factors and RNA-containing exosomes they secrete, rather than their ability to directly replace cells in damaged tissues.
The Nature editorial argues that “wildly varying reports have helped MSCs to acquire a near-magical, all-things-to-all-people quality in the media and in the public mind,” and calls for better characterization of the cells and more rigor in clinical studies.
Emory scientists have identified a way to stop troublemaker cells that are linked to immune rejection after kidney transplant. The finding could eventually allow transplant patients to keep their new kidneys for as long as possible, without the side effects that come from some current options for controlling immune rejection.
The standard drugs used for many years, calcineurin inhibitors, show side effects on cardiovascular health and can even damage the kidneys over time. A newer FDA-approved medication called belatacept, developed in part at Emory, avoids these harmful effects but is less effective at stopping acute rejection immediately after the transplant. Belatacept is a “costimulation blocker” – it interferes with a signal some immune cells (T cells) need to proliferate and become activated.
Researchers led by Emory transplant surgeon Andrew Adams, MD, PhD suspected that long-lasting memory CD8+ T cells were resistant to belatacept’s effects.
“Our previous work identified that memory CD8+ T cells may be elevated in animals and human patients who go on to reject their transplanted organs while taking belatacept,” says Dave Mathews, an MD/PhD student who worked with Adams and is the first author of the paper.
The researchers identified a certain marker, CD122, which was present on memory CD8+ T cells and important for their activity. On T cells, CD122 acts as a receiving dish for two other secreted molecules, IL-2 and IL-15, generally thought of as inflammatory cytokines, or protein messengers that can encourage graft rejection. Read more
Ribosomes, the factories that assemble proteins in cells, read three letters of messenger RNA at a time. Occasionally, the ribosome can bend its rules, and read either two or four nucleotides, altering how downstream information is read: frameshifting.
When mutations add or subtract a letter from a protein-coding gene, that usually turns the rest of the gene to nonsense. Compensatory mutations in the same gene can push the genetic letters back into the correct frame. However, others are separate, found within the machinery for translating the genetic code, namely transfer RNAs: the adaptors that bring amino acids into the ribosome. Suppressor tRNAs can compensate for a forward frameshift in another gene.
The Dunham lab’s new paper solves the structure of a bacterial ribosome undergoing “recoding” influenced by a suppressor tRNA. Her group had previously captured how the ribosomes decode this tRNA in one site of the ribosome, the aminoacyl or A site, in a 2014 PNAS paper. The new structures show how the tRNA moves through the ribosome out-of-frame to recode. The tRNA undergoes unusual rearrangements that cause the ribosome to lose its grip on the mRNA frame and allows the tRNA to form new interactions with the ribosome to shift into a new reading frame.
There’s a bit of sugar attached to your billion-dollar biotech product. Omitting the sugar (fucose) can help the product work better, Emory immunologists think.
Fucosylation is the red triangle on this diagram of the carbohydrate modifications of antibodies. Adapted from KTC Shade + RM Anthony, Antibodies (2013) and used through Creative Commons license.
Many drugs now used to treat cancer and autoimmune diseases are antibodies, originally derived from the immune system. A classic example of a “therapeutic antibody” is rituximab, a treatment for B cell malignancies that was FDA-approved in 1997. It has been responsible for billions of dollars in revenue for its maker, pharmaceutical giant Roche.
Researchers at Emory Vaccine Center previously observed that in a mouse model of chronic viral infection, a traffic jam inside the body limits how effective therapeutic antibodies can be. One of the ways these antibodies work is to grab onto malignant or inflammatory cells. One end of the antibody is supposed to bind the target cell, while another is a flag for other cells to eliminate the target cell. During a chronic viral infection, a mouse’s immune system is producing its own antibodies against the virus, which form complexes with viral proteins. These immune complexes prevented the injected antibodies from depleting their target cells.
In a recent Science Immunology paper, postdoc Andreas Wieland, Vaccine Center director Rafi Ahmed and colleagues showed that antibodies that lack fucosylation have an enhanced ability to get rid of their intended targets. Fucosylation is a type of sugar modification of the antibody. (It is the red triangle in the diagram, provided by Wieland.) When it is not present, then the “flag for removal” region of the antibody can interact more avidly with the Fc gamma receptor on immune cells. Thus, the introduced antibodies can compete more effectively with the antibodies being produced by the body already.
In November, Emory’s Office of Postdoctoral Education will be having a workshop on science writing in November, with special guest Marina Damiano. She is a scientist with corporate experience at an advertising/marketing communications/PR agency for life science and healthcare companies. While her workshop is now overscheduled (suggesting an abundance of interest!), Damiano is giving a career talk as well.
• Career Seminar. Wed, Nov 14th, 12 – 1.30 pm, SOM 178-P Hear Damiano discuss her background and career path, giving advice for anyone interested in pursuing a career in science communications. Open to everyone: undergraduates, grad students and postdocs.
Almost precisely a decade ago, a young Atlanta lawyer named Anna was returning to work, after being treated for an extraordinary sleep disorder. Her story has been told here at Emory and by national media outlets.
Fast forward a decade to Idiopathic Hypersomnia Awareness Week 2018 (September 3-9), organized by Hypersomnolence Australia. What this post deals with is essentially the correction of a date at the tail end of Anna’s story, but one with long-term implications for many people with difficult-to-treat sleep disorders.
In the summer of 2008, Anna Sumner (now Pieschel) was planning on getting back to her life and career. A few years before, she had been diagnosed with a condition with a frustrating name: idiopathic hypersomnia. It means “she sleeps a lot and we don’t know why.”
Neurologist David Rye and nurse practitioner Kathy Parker had treated Anna first with conventional stimulants, which were spectacularly unsatisfactory. See this 2013 Emory Medicine story for details. Parker and Rye eventually landed on something less conventional: flumazenil, an antidote for sedatives that was scarce and difficult to administer. After wrangling with the FDA and with flumazenil’s manufacturer, a longer-term solution came into view. At that time, Anna was unique: the only person taking flumazenil chronically for a sleep disorder.
Then she developed bronchitis. She lost her voice, which was a problem for someone whose professional role sometimes takes her to court. To treat her bronchitis, Anna’s internist had prescribed the antibiotic clarithromycin, known commercially as Biaxin. After taking it, she developed insomnia and couldn’t sleep for three days. She left frantic messages for neurologist Lynn Marie Trotti, who had become her main sleep specialist.
“This had never happened to me before,” she recalled recently. “I was concerned that it was some bizarre individual reaction to the medication.”
In our original Emory Medicine story, this event was described as taking place in 2010. That date was incorrect. Read more
After a heart attack, cardiac muscle cells die because they are deprived of blood and oxygen. In an adult human, those cells represent a dead end. They can’t change their minds about what kind of cell they’ve become.
In newborn babies, as well as in adult fish, the heart can regenerate after injury. Why can’t the human heart be more fishy? At Emory, researcher Jinhu Wang is seeking answers, which could guide the development of regenerative therapies.
“If we want to understand cardiac regeneration in mammals, we can look at it from the viewpoint of the fish,” he says.
A lot of research in regenerative medicine focuses on the potential of stem cells, which have not committed to become one type of tissue, such as brain, skin or muscle. Wang stresses that the ability of zebrafish hearts to regenerate does not originate from stem cells. It comes from the regular tissues. The cells are induced to go back in time and multiply, although their capacity to regenerate may vary with the age of the animal, he says.
Jinhu Wang, PhD manages an impressive set of fish tanks
Zebrafish hearts are simpler than mammals’: theirs have just two chambers, while ours have four. Nobel Prize winner Christiane Nusslein-Vollhard has promoted the use of zebrafish as a genetic model in developmental biology. Its embryos are transparent, making it easy to spot abnormalities.
Wang’s fish room in the basement of Emory’s Rollins Research Center contains more than 1000 fish tanks, with different sizes of cage for various ages and an elaborate water recycling system. The adult fish eat brine shrimp that are stored in vats in one corner of the lab. Read more
Last week, Lab Land put out a Twitter poll, touching on the cognitive distortions that make it difficult to do high-quality science. Lots of people (almost 50) responded! Thank you!
We had to be vague about where all this came from, because it was before the publication of the underlying research paper. Ray Dingledine, in Emory’s Department of Pharmacology, asked us to do the Twitter poll first, to see what answers people would give. Dingledine’s paper in eNeuro is now published, so we can explain.
Raymond Dingledine, PhD
The paper is titled “Why Is It So Hard To Do Good Science?” Basically, Dingledine argues, our cognitive biases get in the way. eNeuro summarizes the take-home message this way: “Improving experimental design and statistical analyses alone will not solve the reproducibility crisis in science.”
When designing their experiments, Dingledine says, scientists need to take account of “the law of small numbers”—the distortions random variation can introduce when sample sizes are small – along with other cognitive biases.
In the 1960s and 1970s, psychologists Daniel Kahneman and Amos Tversky demonstrated that people tend to engage in “fast thinking” — relying on preconceived notions and emotions — when making decisions in the face of new information. In his update of this research, Dingledine found that scientists of all career stages are subject to the same biases as undergraduates when interpreting data.
The findings reinforce the roles that two inherent intuitions play in scientific decision-making: our drive to create a coherent narrative from new data regardless of its quality or relevance, and our inclination to seek patterns in data whether they exist or not. Moreover, we do not always consider how likely a result is regardless of its P-value.Read more