It may seem like a stretch to compare an enzyme to a notorious criminal, especially one as distinctive as Omar Little, a character from the HBO drama The Wire played by Michael Kenneth Williams.
But stick with me, Iâ€™ll explain.
Omar is a stick-up man who robs street-level drug dealers. When drug dealer henchmen Stinkum and Weebay ambush him, they are unsuccessful and Stinkum is killed. Omar tells Weebay, who is hiding behind a car: â€œCome at the king, you best not miss.â€
At Emory, Ed Mocarski, Bill Kaiser and colleagues at GlaxoSmithKline have been studying an enzyme called RIP3. RIP3 is the king of a formÂ of programmed cell death called necroptosis. RIP3 is involved in killing cells as a result of several inflammation-, infection- or injury-related triggers, so inhibitors of RIP3 could be useful in modulating inflammation in many diseases.
In a new Molecular Cell paper, Mocarski, Kaiser and their co-authors lay out what happened when they examined the effects of several compounds that inhibit RIP3 in cell culture. These compounds stopped necroptosis, but unexpectedly, they unleashed apoptosis, another form of programmed cell death.Â Read more
Flagellin is a bacterial protein that activates the innate immune system. Its name comes from flagella, the whips many bacteria use to propel themselves.
On Thursday, a team of researchers led by immunologist Andrew Gewirtz reported in ScienceÂ that treatment with flagellin can prevent or cure rotavirus infection in animals. Rotavirus infection is one of the most common causes of severe diarrhea and is a major cause of death for children in developing countries.
Andrew Gewirtz, PhD
Gewirtzâ€™s lab is now at Georgia State, but he and his colleagues initiated this research while at Emory and several co-authors are affliliated with Emory, including immunologist Ifor Williams.
These findings are remarkable for several reasons. One is: give the immune system something from bacteria, and itâ€™s better at fighting a virus? As Gewirtz says in a GSU news release: â€œItâ€™s analogous to equipping an NFL defense with baseball bats. Blatant violation of all the rules but yet, at least in this case, very effective.â€
For me, what was most surprising about this paper was that treatment with flagellin, or immune signaling proteins activated by flagellin, can get mice with severely impaired immune systems â€“ no T cells or B cells at all — to evict rotavirus. These are mice that have to be reared under special conditions because they are vulnerable to other infections. Interferons, well-known antiviral signaling molecules, are also not involved in resisting or evicting rotavirus infection, the researchers found. Read more
This piece in the Los Angeles Times gives a helpful preview of what Paul Offit’s talk at Emory next weekÂ may be like. He also gave a keynote speech at the Association for Health Care Journalists meeting this spring.
OffitÂ isÂ the chiefÂ ofÂ theÂ DivisionÂ ofÂ Infectious DiseasesÂ andÂ theÂ DirectorÂ ofÂ the VaccineÂ EducationÂ CenterÂ at theÂ Childrenâ€™sÂ HospitalÂ ofÂ Philadelphia. He is speaking at noon at the Health Sciences Research Building Auditorium on Nov. 18.
Offit is also speaking that morning at Childrens’ Scottish Rite hospital on the 1991 measles outbreak in Philadelphia.Â The emails I’ve been getting for the noonÂ eventÂ ask people to register.
Anita McElroy, a pediatric infectious disease specialist at Emory, and her colleagues at the CDC, led by Christina Spiropoulou, have been getting some attention for their biomarker research on Ebola virus infection. Sheri FinkÂ from the New York Times highlighted their work in a Nov. 9 report on the infection’s capriciousness. Genetics may also play a role in surviving Ebola infection, as recent animal research has suggested.
McElroy’s team’s findings attracted notice because their results suggest that Ebola virus disease may affect children differently and thus, children may benefit from different treatment regimens than those for adults. The authors write that early intervention to prevent injury to the lining of blood vessels — using statins, possibly — might be a therapeutic strategy in pediatric patients. Read more
It arises from what scientists previously described as â€œjunk DNAâ€ or â€œthe dark matter of the genome,â€ but this gene is definitely not junk. The gene Gas5Â acts as a brake on steroid hormone receptors, making it a key player in diseases such as hormone-sensitive prostate and breast cancer.
Unlike manyÂ genes scientists are familiar with, Gas5Â does not encode a protein. It gets transcribed into RNA, like manyÂ other genes, but with Gas5Â the RNA is whatâ€™s important, not the protein. The RNA accumulates in cells subjected to stress and soaks up steroid hormone receptors, preventing them from binding DNA and turning genes on and off.
Emory researchers have obtained a detailed picture of how the Gas5 RNA interacts with steroid hormone receptors. Their findings show how the Gas5 RNA takes the place of DNA, and give hints as to how it evolved.
The results were published FridayÂ in Nature Communications.
Scientists used to think that much of the genome was â€œfly-over countryâ€: not encoding any protein and not even accessed much by the cellâ€™s gene-reading machinery. Recent studies have revealed that a large part of the genome is copied into lincRNAs (long intergenic noncoding RNAs), of which Gas5 is an example. Read more
On Oct. 24, the Food and Drug Administration approved Obizur, a treatment for acquired hemophilia A. Obizur was originally developed by a research team led by Emory hematologist Pete Lollar. The Obizur technology was licensed by Emory in 1998 to startup company Octagen (more about Octagen from Philadelphia Business Journal) and eventually brought to commercial availability by the pharmaceutical firm Baxter International.
Lollar is Hemophilia of Georgia Professor of Pediatrics in the Aflac Cancer and Blood Disorders Center at Emory University School of Medicine and Childrenâ€™s Healthcare of Atlanta. The team that developed the drug included Ernest Parker, John Healey and Rachel Barrow, and followedÂ a research collaboration between Lollar and Emory cardiologist Marschall Runge (now at UNC).
Hemophilia is a group of blood clotting disorders leading to excessive bleeding that can occur spontaneously or following injury or surgery. Hemophilia A is caused by a deficiency of clotting factor VIII, and can be either inherited or acquired.
In acquired hemophilia A, the immune system is somehow provoked into making antibodies against factor VIII that inactivate it. Acquired hemophilia is a challenge for doctors to deal with because patients frequently present with severe, life threatening bleeding and also because itâ€™s a surprise: patients do not have a previous personal or family history of bleeding episodes. Antibodies to factor VIII also can be a problem for approximately 30 percent of patients with inherited hemophilia.
Lollar’s team developed a modified form of factor VIII, derived from the protein sequence of pigs, which is less of a red flag to the immune system. Read more
What conferences likeÂ the HIV + Aging meeting recently held byÂ Emory in Decatur offer the visiting writer: anecdotes that illustrate issuesÂ of clinical care.
To illustrate her point that assumptions about who is likely to develop a new HIV infection may lead doctors to miss possible diagnoses, keynote speaker Amy Justice from Yale described a patient who was seen last year at Yale-New Haven Hospital.
AÂ 60 year old man reported fatigue and had lost 40 pounds over the course of a year. Despite those symptoms, and the discovery of fungal and viral infections commonlyÂ linked to HIV/AIDS, it took nine months before a HIV test wasÂ performed on the patient, a delay Justice deplored.
Sex and substance abuse do not end at age 50, she said, citing data showing that the risk of HIV transmission can be greater among older adults, and that substance abuse is more likely among adults who are HIV positive compared to those who are HIV negative.
Justice also highlighted the issue of polypharmacy (interactions betweenÂ prescription drugs at the same time), a concern even inÂ peopleÂ who are not living with HIV. Common blood pressure medications taken by older adults to prevent heart disease have been suspected of increasing the risk for falls. That’s a problem especially for people living with HIV, because HIV infection has been linked to weakened bone. Read more
From left: RSPH dean Jim Curran, First Lady Jeannette Kagame, HIV/AIDS researcher Susan Allen, Vice Provost Philip Wainwright
Most of the discussion, when Rwanda’s First Lady Jeannette Kagame recently visited Emory, was not about HIV vaccines, and rightly so. It was about how far Rwanda has come as a country since the 1994 genocide [videos of author Philip Gourevitch discussing Rwanda].
Still,Â while introducing the First Lady and thanking her for her support of HIV/AIDS research in Rwanda, Susan Allen mentioned a clinical trial for a HIV vaccine that began last year in Rwanda, Kenya and the United Kingdom and is now wrapping up the vaccination phase. Her colleague in Kigali, Etienne Karita, is one of the principal investigators.
The vaccine uses replicating Sendai virus, which causes respiratory tract illness in rodents but not in humans, as a vector to deliver the HIV gag gene. The trial combines this vaccine, administered intranasally, in various configurationsÂ with an adenovirus-based vaccine. This is the first time that Sendai virus is beingÂ used in a HIV vaccine.
As IAVI Report’s Regina McEnery explains,Â researchers hope the Sendai vector might recruit targeted immune responses to mucosal tissues and provide an edge to the immune system when it is subsequently challenged by HIV.
In a future post, we plan to provide an additional update on HIV vaccine research, focusing on GeoVax and (separate, for comparison) a planned large-scale followup to the landmark RV144 Thai trial.
This complex diagram, showing the gene segments that encode lamprey variable lymphocyte receptors, comes from a recent PNAS paper published by Emory’s Max Cooper and his colleagues along with collaborators from Germany led by Thomas Boehm. Lampreys have moleculesÂ that resemble our antibodies in function, but theyÂ look very different at the protein level. The study of lamprey immunityÂ provides hints to how the vertebrate immune system has evolved.