Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more
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Shedding light on the vitamin D-Parkinson’s connection

Vitamin D may be called a vitamin, but it’s not. That’s because we can make it by exposing our skin to sunshine. So, technically that makes vitamin D a hormone–a steroid hormone to be exact. In fact, we get most of our exposure to vitamin D directly from sunshine and some from foods such as milk, fortified orange juice and oily fishes like salmon.

But no matter what you call it or where you get it, vitamin D is vital to growth, development and maintenance of our cells. Doctors have known for decades that vitamin D promotes calcium uptake and bone formation, but evidence is accumulating that it regulates the immune system and the development of the nervous system. Growing evidence suggests a link between low vitamin D levels and Parkinson’s disease, but whether this is a cause-and-effect relationship is unknown.

Marian Evatt, MD

That’s why Emory neurologist Marian Evatt, MD, and her colleagues are conducting a clinical trial exploring the effects of vitamin D supplementation on patients with Parkinson’s disease who have low vitamin D levels. The study also includes further epidemiological studies of vitamin D in Parkinson’s disease.

Parkinson’s disease affects nerve cells in several parts of the brain, particularly those that use the chemical messenger dopamine to control movement. The most common symptoms of Parkinson’s disease are tremor, stiffness and slowness of movement.

“Vitamin D has become associated with many chronic diseases: diabetes, hypertension, cardiovascular disease, and some of the autoimmune diseases, including multiple sclerosis,” says Evatt. “But we haven’t yet determined the specific effect of vitamin D in specific conditions because it has such broad effects.”

To hear Evatt talk about what vitamin D is, what it does, and why we need it, please go to Emory’s latest Sound Science podcast.

Posted on October 18, 2010 by admin in Neuro Leave a comment

A path to treatment of lymphedema

Lymphedema, or swelling because of the impaired flow of lymph fluid, can occur as a consequence of cancer or cancer treatment. Chemotherapy can damage lymph ducts, and often surgeons remove lymph nodes that may be affected by cancer metastasis. Lymphedema can result in painful swelling, impaired mobility and changes in appearance.

Young-sup Yoon, MD, PhD

Emory scientists, led by cardiologist and stem cell biologist Young-sup Yoon, have shown that they can isolate progenitor cells for the lining of lymph ducts. This finding could lead to doctors being able to regenerate and repair lymph ducts using a patient’s own cells. The results are described in a paper published recently in the journal Circulation.

The authors used the cell surface marker podoplanin as a handle for isolating the progenitor cells from bone marrow. Previous research has demonstrated that podoplanin is essential for the development of the lymphatic system.
In the paper, the authors use several animal models to show that the progenitor cells could contribute to the formation of new lymph ducts, both by becoming part of the lymph ducts and by stimulating the growth of nearby cells.

“This lymphatic vessel–forming capability can be used for the treatment of lymphedema or chronic unhealed wounds,” Yoon says.

Isolated lymphatic endothelial cells (red) incorporate into lymph ducts (green) in a model of wound healing in mice.

The authors also show that mice with tumors show an increase in the number of this type of circulating progenitor cells. This suggests that tumors send out signals that encourage lymph duct growth – a parallel to the well-known ability of tumors to drive growth of blood vessels nearby. Yoon says the presence of these cells could be a marker for tumor growth and metastasis. Because tumors often metastasize along lymph ducts and into lymph nodes, studying this type of cells could lead to new targets for blocking tumor metastasis.

A recent review in the journal Genes & Development summarizes additional functions of the lymphatic system in fat metabolism, obesity, inflammation, and the regulation of salt storage in hypertension.

Posted on October 13, 2010 by Quinn Eastman in Cancer Leave a comment

Adjuvants: once immunologists’ “dirty little secret”

Two presentations on Emory research at last week’s AIDS Vaccine 2010 conference concerned adjuvants. These are substances that act as amplifiers, stimulating the immune system while keeping its focus on the specific components of a vaccine.

Charlie Janeway (1943-2003)

Immunologist Charlie Janeway once described adjuvants as immunology’s “dirty little secret,” because for a long time scientists did not know how they worked. Some adjuvants can sound irritating and nasty, such as alum and oil emulsion. Alum is the only vaccine adjuvant now licensed for human clinical use in the US. Over the last few years, scientists have learned that adjuvants rev up what is now known as the “innate immune system,” so that the body knows that the vaccine is something foreign and dangerous.

Rama Rao Amara, a vaccine researcher at Emory Vaccine Center and Yerkes National Primate Research Center, and Harriet Robinson, former head of microbiology and immunology at Yerkes and now chief scientific officer at the firm GeoVax, both described extra ingredients for the DNA/MVA vaccine that Robinson designed while at Yerkes in collaboration with NIH researchers.

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Posted on October 8, 2010 by Quinn Eastman in Immunology Leave a comment

What if HIV was just another virus

Imagine that HIV was a “normal” virus. An infection begins and the body responds, without getting trapped in a cycle where CD4+ T cells are consumed and the immune system is crippled.

SIV can infect sooty mangabeys but it doesn't cripple their immune systems.

The attractiveness of this idea explains some of why scientists are interested in sooty mangabeys and other non-human primates. HIV’s relative SIV can infect them, but they usually don’t develop immunodeficiency.

At last week’s AIDS Vaccine 2010 conference, Cynthia Derdeyn reported her laboratory’s recent results investigating sooty mangabeys, which don’t develop high levels of neutralizing antibodies against SIV when infected. Derdeyn’s group at Emory Vaccine Center and Yerkes National Primate Research Center studies how HIV and SIV evade the immune system.

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Posted on October 7, 2010 by Quinn Eastman in Immunology Leave a comment

Re-energizing AIDS vaccine research

Emory President James Wagner welcomed participants Wednesday to the AIDS Vaccine 2010 conference in Atlanta, hosted by the Global HIV Vaccine Enterprise and locally hosted by the Emory Center for AIDS Research.

“Only occasionally are there scientific challenges that unite people powerfully towards a common goal,” Wagner said. “We are proud for the role we’ve been able to play in the pursuit of vaccine research. I am particularly pleased that so many students and young investigators have been able to participate in this conference.”

John Mascola from the Vaccine Research Center at the NIH gave the day’s first scientific talk, describing the discovery of broadly cross-reactive neutralizing antibodies to HIV and the ability to isolate those antibodies. This is the kind of recent discoveries that has re-energized the HIV vaccine research community.

Bette Korber of the Los Alamos National Laboratory noted that HIV mutations that escape immune response in some infected people are frequently susceptible in others. New “mosaic vaccines” can expand the breadth and depth of these immune responses, she said. She also described the effort underway in her laboratory to re-examine results of an earlier vaccine trial, VAX004, in light of new analytic strategies.

Giuseppe Pantaleo of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland expressed the need to implement adaptive clinical trial study design. This theme — the need to examine clinical trial results early and often, and then adapt, rather than waiting for all results at the very end of a years-long trial — has been echoed often at the conference.

At a midday press briefing, Peter Kwong of the NIH Vaccine Research Center discussed his research with broadly neutralizing antibodies, one of which attacks the initial site of vital attachment to CD4 T cells.

Hendrik Streek from Harvard’s Ragon Institute described how vaccines induce antibody and CD4 response and contraction. Even though CD4 cells are the ones attacked during HIV infection, Streek believes CD4 responses may be a missing link to effective vaccine development

Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, led a discussion of the new Enterprise Scientific Strategic Plan. Less than two out of five people who need treatment for HIV are receiving it, said Bernstein, which underscores the importance of an effective vaccine.

The new plan arrives at a time of great momentum and excitement in the field. A year of important advances has included discoveries about broadly neutralizing antibodies, new technologies, and a vaccine that demonstrated an immune response. The plan emphasizes novel clinical trials design, a strong commitment and engagement by many partners, and expanded diversity of funding by many stakeholders.

Jose Esparza, senior advisor on HIV vaccines to the Bill & Melinda Gates Foundation, emphasized the need to rapidly capitalize on new science, and said HIV vaccines are one of the foundation’s top priorities. High risk, high reward projects will be funded through the Gates Grand Challenges Explorations grants.

Posted on September 30, 2010 by admin in Immunology Leave a comment

Strengthening community engagement in HIV vaccine research

Paula Frew, PhD

The scientific part of the AIDS Vaccine 2010 meeting began Tuesday evening with an exciting summary of issues facing the field from NIAID director Tony Fauci. But before that, participants in this year’s conference got a chance to warm up with several “satellite sessions.”

One of them, “Effective Community Engagement in HIV Vaccine Research Among Communities and Researchers,” was organized by Paula Frew, PhD, director of health communications and applied community research at Emory’s Hope Clinic.

Two prominent themes emerged from this session. The first was that community members should be involved in clinical trials at every step of the process: from design and recruitment to dissemination of results.

“In the past, scientists often came to the community late in the process, after a protocol for a study was already approved, and said: “Will you support what we’ve already decided?” said Steve Wakefield of HIV Vaccine Trials Network. “This doesn’t work.”

The Joint United Nations Programme on HIV/AIDS and AVAC presented proposed guidelines for “good participatory practice,” analogous to good clinical practices.

Another theme that emerged from the satellite session was the search for more flexible “adaptive” clinical trial formats. Glenda Gray from South Africa’s University of the Witwatersrand emphasized that adaptive trials could be faster and avoid enrollment of large numbers of patients unnecessarily.

Posted on September 30, 2010 by Quinn Eastman in Immunology Leave a comment

AIDS Vaccine 2010 conference brings global research focus to Atlanta

This week’s AIDS Vaccine 2010 conference, Sept. 28-Oct. 1, is underway at Atlanta’s Omni Hotel. Under the auspices of the Global HIV Vaccine Enterprise, the international meeting is hosted by the Emory Center for AIDS Research (CFAR).

Over 1,100 scientists, advocates, funders, and policy makers are attending 500 sessions about scientific discoveries and future directions for developing an effective HIV/AIDS vaccine. This goal is considered critical in fighting the ongoing epidemic, which newly infects 50,000 people each week around the world.

Emory HIV/AIDS researchers are playing a significant role in the meeting. The four co-chairs are Eric Hunter, PhD, co-director of the Emory CFAR; James Curran, MD, MPH, dean of Emory’s Rollins School of Public Health and co-director of the CFAR; Carlos del Rio, MD, chair of the Hubert Department of Global Health and co-chair of the CFAR; and Harriet Robinson, PhD, formerly of Yerkes Primate Center and Emory Vaccine Center and now at GeoVax, Inc.

Hunter led the opening press conference and opening session on Tuesday afternoon.

A fellowship program hosted 21 journalists from media outlets around the world.

Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, emphasized the need to build a bridge between basic science and clinical research. On Wednesday, Bernstein will talk about the Enterprise’s new strategic plan for an HIV vaccine.

Dazon Dixon Diallo, director of the African-American women’s organization Sisterlove, noted that the South has been particularly hard hit by the AIDS epidemic, with over half the HIV cases in the United States. The human rights dimensions of the disease are enormous, she said, and engagement with community partners is essential in fighting HIV. Researchers need to solve the problem with the help of people who know the most about it.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases of the NIH, said that even though the road to an HIV vaccine has been a rocky one over the past 23 years, the limited success reported last year with the RV144 trial was the first signal that it is possible for a vaccine to block HIV acquisition, a finding that has re-energized the vaccine community.

Future directions for HIV vaccine research, said Fauci, will include research that builds on insights from the success of RV144, multiple clinical trials conducted as scientific tools and not just all-or-nothing aims for vaccine licensing, more research into the early events of HIV infection that could provide targets for vaccines, and new structure-based vaccines using newly discovered neutralizing antibodies.

“I don’t think there is any question we are going to get there,” said Fauci. “The light at the end of the tunnel is the science we are now implementing.”

Press conferences are streamed live and available for playback at the conference website:

For more information on Emory’s role in the conference and Emory HIV/AIDS research, including video, see the website.

Posted on September 28, 2010 by admin in Immunology Leave a comment

Smart mice, clever names and some context

This week a variety of media outlets and science-oriented Web sites had fun with research at Emory — published recently in PNAS — investigating a gene that appears to limit some forms of learning and memory.

Mice with a disabled RGS14 gene remembered objects in their cages more easily and learned to navigate water mazes better, pharmacologist John Hepler and his colleagues found. Since the presence of a functional RGS14 gene holds mice back mentally, Hepler and his colleagues have been jokingly calling it “the Homer Simpson gene.”

This description struck a chord; the Atlantic magazine even embellished the story with a video showing the “D’oh”-ey cartoon character evolving from a single cell into a human couch potato.

It’s important to recognize that smart mice are not so surprising to scientists anymore. Back in 1999, scientists at Princeton announced the creation of “Doogie Howser” mice (named after a precocious doctor from another TV series). These critters performed better than normal lab mice in some of the same tests that Hepler’s team used to evaluate the RGS14-deleted mice.

One important difference: the Doogie mice had all their normal genes, and were overproducing a NMDA receptor gene involved in helping neurons communicate. Still, as a helpful 2009 round-up in Nature Reviews Neuroscience explains, scientists have found several single-gene knock-out mice that do better on tests of learning and memory. Many of these genetic alterations affect the process of long term potentiation, a process where neurons that get stimulated at the same time have the connections between them grow stronger.

RGS14 is turned on primarily in the CA2 region of the hippocampus

What makes the RGS14 gene an intriguing case is that it’s primarily turned on in the enigmatic CA2 region of the hippocampus. The CA2 region is normally relatively resistant to long-term potentiation and is also more hardy in situations of stroke or seizure.

Hepler observes that the vasopressin receptor 1b gene is also turned on predominantly in the CA2 region, and seems to be involved in aggression and social memory. He and his colleagues are planning to examine whether the RGS14-disabled mice have altered capabilities in those areas. Conveniently, Larry Young’s laboratory at Yerkes National Primate Research Center has been investigating the functions of vasopressin receptors in voles.

One last note: scientists in Spain have reported in Science that they can generate a variety of smart mice by putting the RGS14 gene on overdrive in a part of the brain where it’s not usually turned on. So whatever precise function RGS14 has, it doesn’t always dumb things down.

Posted on September 27, 2010 by Quinn Eastman in Neuro 1 Comment

Initial Results of Heart Valve Study Encouraging

 

Emory heart patient, Glenrose Gay of Vidalia was the first person in GA to receive a new aortic valve via catheter. Pictured here in 2007 with Emory cardiologists, Drs. Peter Block (left) and Vasilis Babaliaros.

Since October 2007, Emory University Hospital has been one of approximately 20 hospitals nationwide, and the only site in Georgia, studying a new non-surgical treatment option for patients with failing aortic valves. The life threatening heart condition,aortic stenosis, affects tens of thousands of Americans each year when the aortic valve tightens or narrows, preventing blood from flowing through normally.

As part of the Phase II clinical trial, researchers have been performing transcatheter aortic valve implantation (TAVI) comparing this procedure with traditional, open-heart surgery or medical therapy in high-risk patients with aortic stenosis.

During the TAVI procedure, doctors create a small incision in the groin or chest wall and then feed the new valve, mounted on a wire mesh on a catheter, and place it where the new valve is needed. This offers a non-invasive way for doctors to treat patients who are too ill or frail to endure the traditional open-heart surgical approach.

The study, published Wednesday in The New England Journal of Medicine (NEJM) followed 358 patients who received either catheter-delivered valves or standard non-surgical treatment.

The findings showed that patients who had replacement heart valves delivered by catheter were more likely to survive a year than patients who were treated without replacing their original valves. According to the authors, catheter-delivered valves “should be the new standard of care” for patients who are not able to undergo surgery.

“These results show great promise for patients with severe aortic stenosis and help us make a giant step forward in our battle against this common disease,” says Peter Block, MD, professor of medicine, Emory School of Medicine and principal investigator of the study at Emory. “They are especially important since the number of people with failing valves is expected to greatly increase as baby boomers continue to age.”

Aortic valve stenosis often occurs with age, most commonly among elderly patients over 70 years of age, but can surface earlier in life in those with rheumatic heart disease or congenital abnormalities of the valve.

Approximately 90 patients have received new valves at Emory since the clinical trial started in 2007. Researchers hope to receive FDA approval in late 2011.

Posted on September 24, 2010 by admin in Uncategorized Leave a comment

Global health: from autism screening to neglected tropical diseases

A partnership of more than 40 universities, the Consortium of Universities for Global Health held its second annual meeting at the University of Washington in Seattle this week, with a wide range of presentations centered on the theme Transforming Global Health: The Interdisciplinary Power of Universities.  Emory Global Health Institute presentations ranged from neglected tropical diseases to autism in Chinese populations to changes in medical school curricula.

Carlos Franco-Paredes, MD

Emory’s Carlos Franco Paredes, MD, MPH, associate professor of medicine (infectious disease) talked about a troublesome global health issue—one that hits close to home—the effect of neglected tropical diseases in the immigrant and refugee communities living in Atlanta. Neglected tropical diseases are disabling, disfiguring, and deadly diseases impacting more than one billion people worldwide, says Paredes. Atlanta’s immigrant populations show a high prevalence of intestinal parasitic infections, schistosomiasis, strongyloidiasis, and hepatitis B.

Meanwhile, Joseph Cubells, MD, associate professor of human genetics at Emory, shared his experience with the Mandarin Chinese Autism Spectrum Screening Questionnaire in urban Mandarin Chinese-speaking communities. Cubells says large-scale, community-based studies of autism spectrum disorders require effective tools for screening potential cases. So, to meet the need for such tools in Chinese populations, he and his colleagues translated and back-translated The Autism Spectrum Screening Questionnaire, a 27-item parental checklist originally published in English.

And what about incorporating global health education into the medical curriculum as a way of transforming universities’ role in advancing global health? Emory’s Henry Blumberg, MD, professor of infectious disease and his colleagues have done just that. Now, global health is a part of Emory’s innovative new medical curriculum, which was launched in 2007. After all, global health is becoming ever more important to the world at large, garnering more interest from future physicians.


Posted on September 22, 2010 by admin in Uncategorized Leave a comment
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