It arises from what scientists previously described as “junk DNA” or “the dark matter of the genome,” but this gene is definitely not junk. The gene Gas5 acts as a brake on steroid hormone receptors, making it a key player in diseases such as hormone-sensitive prostate and breast cancer.
Unlike many genes scientists are familiar with, Gas5 does not encode a protein. It gets transcribed into RNA, like many other genes, but with Gas5 the RNA is what’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 Friday in Nature Communications.
Scientists used to think that much of the genome was “fly-over country”: not encoding any protein and not even accessed much by the cell’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.
Vaccine researchers have developed a strategy aimed at generating broadly cross-reactive antibodies against the influenza virus: embrace the unfamiliar.
In recent years, researchers interested in a “universal flu vaccine” identified a region of the viral hemagglutinin protein called the stem or stalk, which doesn’t mutate and change as much as other regions and could be the basis for a vaccine that is protective against a variety of flu strains.
In an Emory Vaccine Center study, human volunteers immunized against the avian flu virus H5N1 readily developed antibodies against the stem region of the viral hemagglutinin protein. In contrast, those immunized with standard seasonal trivalent vaccines did not, instead developing most of their antibodies against the more variable head region. H5N1, regarded as a potential pandemic strain, is not currently circulating in the United States and the volunteers had not been exposed to it before.
The results were published Monday, August 25 inÂ PNAS.
The key to having volunteers’ bodies produce antibodies against the stem region seemed to be their immune systems’ unfamiliarity with the H5N1 type of virus, says lead author Ali Ellebedy, PhD, postdoctoral fellow in the laboratory of Rafi Ahmed, PhD, director of Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.
Note: for a counterpoint, check out this 2013 Science Translational Medicine paper on how vaccination that induces anti-stem antibodies contributes toÂ enhanced respiratory disease in pigs.
While preparing to discuss Ebola virology with Emory infectious disease specialist Aneesh Mehta next week, we noticed two recent research papers on which he is a co-author. Both have to do with organ transplantation, since Mehta isÂ Assistant Director of Transplant Infectious Diseases.
Fecal microbiota transplantation for refractory Clostridium difficile colitis in solid organ transplant recipients
Fecal transplant is gaining ground as a remedy for C. difficile-driven diarrheal infections, which can appear in patients whose normal intestinal bacteria are wiped out by antibiotics. Fecal transplant has not been widely studied in organ transplant recipients, who must take drugs to keep their immune systems from rejecting the transplanted organ, because of concerns about infectious disease complications. This paper describes two patients, one a lung transplant recipient and one a kidney transplant recipient, who received fecal transplants to resolve their C. difficile diarrhea without complications. The lead authors are infectious disease specialists Rachel Friedman-Moraco and Colleen Kraft. Kraft has beenÂ a pioneer in this area of research.
Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors
Medical school dean Chris Larsen and Emory Transplant Center executive director Tom Pearson (both co-authors) were key members on the team that developedÂ belatacept, a FDA-approved drug since 2011. Belatacept was designed to get away fromÂ the cruel paradox where a kidney recipient, to prevent transplant rejection, has to take calcineurin inhibitor drugs that slowly poison the kidney and cardiovascular health. Belatacept inhibits the immune response by a different mechanism. Yet transplant specialists have generally been cautious in moving toward a regimen that relies on it.
As reportedÂ in this paper, Emory transplant doctors tookÂ off the training wheels, aimingÂ to get to the point where kidney transplant recipients are takingÂ a once-a-month infusion of belatacept only. With some patients, it was possible to reach that goal, but not all. In fact, as the authors describe, some patients chose not to try to wean themselves off the other drugs, and doctors advised against the attempt for a handful. This clinical trial was also notable because some transplant recipients received immune-educational cells from their organ donors in the form of bone marrow.
The lead author, former Emory Transplant Center scientific director Allan Kirk, moved to Duke this spring.
Does hormonal contraception increase the risk for a woman to acquire HIV from an infected partner?
This topic, with implications for public health in countries where HIV risk is high, has been contentious. Some previous studies had found the answer to be yes, for methods involving injectable progesterone such as Depo-Provera. This led the World Health Organization in 2012 to advise women using progesterone-only injections to use condoms to prevent HIV infection.
At the recent AIDS 2014 meeting in Australia, Emory epidemiologist Kristin Wall presented data from public health programs in Zambia. This is another study emerging from the Zambia-Emory HIV Research Project directed by Susan Allen.
Wall’s presentation is available here.
Studying 1393 heterosexual couples with a HIV-positive male partner over 17 years, Wall and her colleagues found no significant difference in incidence rate per 100 couple years between hormonal and non-hormonal forms of contraception. Read more