Quinn Eastman

Reassuring news on viral immunity + HIV vaccine

A recent paper in Journal of Immunology suggests that a platform for an HIV vaccine developed by Yerkes National Primate Research Center scientists won’t run into the same problems as another HIV vaccine. Postdoc Sunil Kannanganat is the first author of the JI paper, with Emory Vaccine Center researcher Rama Amara as senior author.

Harriet Robinson, MD and Rama Rao Amara, PhD

Many HIV vaccines have been built by putting genes from HIV into the backbone of another virus. Some have used a modified cold virus (adenovirus 5). The vaccine developed at Yerkes uses modified vaccinia Ankara (MVA), a relative of smallpox and chicken pox.

Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Challenges in islet transplantation

Two recent research papers from the Emory Transplant Center describe research on pancreatic islet transplantation, an experimental procedure that could help people with type I diabetes live without daily insulin injections.

Islet transplantation may offer people with type I diabetes the ability to produce their own insulin again

As with other types of transplantation, the challenge with islet transplantation is to avoid rejection of the donated organ and to balance that goal against side effects from the drugs needed to control the immune system. These papers illustrate how that balancing act is especially complex.

In the last decade, transplant specialists developed a method for islet transplantation named the “Edmonton protocol” after pioneers at the University of Alberta. While the emergence of this method was a major step forward, there are limitations:

Read more

Posted on by Quinn Eastman in Uncategorized 3 Comments

Secrets of the elite: Effective immune control of HIV

A small minority of individuals infected with HIV — about one in 300 – are naturally able to suppress viral replication with their immune systems, and can keep HIV levels extremely low for years. Doctors have named these individuals “elite controllers.”

“These individuals have naturally achieved the outcome sought by HIV vaccine researchers worldwide.  Studying them will ultimately inform the design of a more effective HIV vaccine,” says Vincent Marconi, a physician-scientist at Grady Health System’s Infectious Disease Clinic on Ponce de Leon and an associate professor in the Emory School of Medicine.

Vincent Marconi, MD

Marconi is a co-author (along with investigators at over 200 institutions) on a genomics study of elite controllers published Thursday in Science Express. Led by Bruce Walker at Massachusetts General Hospital and Paul de Bakker at the Broad Institute and Brigham and Women’s Hospital in Boston, the team of researchers scanned through the genomes of close to 1,000 elite controllers and 2,600 people with progressive HIV infection. They identified several sites linked with immune control of HIV, all in a region encoding HLA proteins.

HLA proteins play key roles in activating T cell immunity, and are also necessary for the development of T cells. They grab onto segments of proteins, called peptides, inside the cell and carry them to the cell membrane. In the right context, certain viral peptides can mark infected cells for destruction by “killer” T cells.

Previously, MGH/MIT researchers theorized that people with certain forms of their HLA genes develop T cells with a restricted repertoire, yet broader activity. Their T cells would be more likely to still recognize HIV when the virus mutates. A drawback is that these individuals may have a higher risk for developing autoimmune diseases. The theory is described in more detail in this Nature News article.

Marconi is continuing his part of this research into what makes elite controllers’ immune systems special, which he began at the Department of Defense Infectious Disease Clinical Research Program, in collaboration with Eric Hunter, co-director of Emory’s Center for AIDS Research, and research associate Ling Yue at Emory Vaccine Center. The research is supported by the Center for AIDS Research and the National Institute of Allergy and Infectious Diseases.

Posted on by Quinn Eastman in Immunology 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 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.

Read more

Posted on 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.

Read more

Posted on by Quinn Eastman 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 by Quinn Eastman 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 by Quinn Eastman in Neuro 1 Comment

Reading the blood: metabolomics

In the Star Trek series, Dr. McCoy could often instantly diagnose someone’s condition with the aid of his tricorder. Medicine on 21st century Earth has not advanced quite this far, but scientists’ ideas of how to use “metabolomics” are heading in this direction.

What is metabolomics? Just as genomics means reading the DNA in a person or organism, and assessing it and comparing it to others, metabolomics takes the same approach to all the substances produced as part of the body’s metabolism: watching what happens to food, drugs and chemicals we are exposed to in the environment.

This means dealing with a huge amount of information. Human genomes may be billions of letters (base pairs) in length, but at least there are only four choices of letter!

A recent article in Chemical & Engineering News explores this concept of the “exposome” and quotes Dean Jones. He and his colleagues recently described how they can use sophisticated analytical techniques to resolve thousands of substances in human plasma. Jones is the director of the Clinical Biomarkers Laboratory at Emory University School of Medicine. The paper is in the journal Analyst, published by the Royal Society of Chemistry.

Analytical techniques can discern more than 2500 metabolites from human plasma within 10 minutes

Using a drop of blood, within ten minutes the researchers can discern more than 2,500 substances in a reproducible way. One fascinating tidbit: when they compared the metabolic profiles for four healthy individuals, most of the “peaks” were common between individuals but 10 percent were unique.

The potential uses for this type of technology are staggering.

Jones reports he has been working with researchers at Yerkes National Primate Research Center to discern early signs of neurodegeneration in transgenic monkeys with Huntington’s disease. He has been collaborating with clinical nutrition specialist Tom Ziegler to examine how diet interacts with oxidative stress, and with lung biology to identify markers for fetal alcohol exposure in animal models.

Posted on by Quinn Eastman in Uncategorized Leave a comment