Drying up the HIV reservoir

Wnt is one of those funky developmental signaling pathways that gets re-used over and over again, whether it’s in the early embryo, the brain or the Read more

Overcoming cardiac pacemaker "source-sink mismatch"

Instead of complication-prone electronic cardiac pacemakers, biomedical engineers at Georgia Tech and Emory envision the creation of “biological Read more

Hope Clinic part of push to optimize HIV vaccine components

Ten years ago, the results of the RV144 trial– conducted in Thailand with the help of the US Army -- re-energized the HIV vaccine field, which had been down in the Read more

immunology

Tailoring transplant drugs for children

For adult organ transplant recipients, juggling a lifetime regimen of immunosuppressant drugs is difficult enough, but for children it presents an even greater challenge.  These drugs, which also can have toxic side effects, must strike a delicate balance between preventing organ rejection and protecting from infections.

But children’s immune systems are still “learning” what distinguishes them from the world around them, and children are constantly developing and changing, both physically and emotionally. This puts them at greater risk for complications either through inappropriate medication or failure to take these drugs properly.

A grant from the National Institute of Allergy and Infectious Diseases (NIAID), through the American Recovery and Reinvestment Act (ARRA), will support new studies at Emory University and Children’s Healthcare of Atlanta to help clinicians tailor therapies specifically for children receiving transplants.  The project will include hiring of additional personnel to undertake these studies.

Allan D. Kirk, MD, PhD, is principal investigator of the project, which is supported by a two-year grant of nearly $1.65 million. Kirk is professor of surgery and pediatrics in Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar. He also is vice chair of research in the Department of Surgery and scientific director of the Emory Transplant Center.

The ARRA-funded project will not only help determine which medications children should take, but also will give them the support to care for their transplanted organs.  The Emory scientists are studying new biological monitoring technologies that can identify unique ways to determine exactly how much medication a child really needs. These studies are being combined with a novel transition care clinic specializing in helping children cope with their illness and assuming responsibility for their care.

“This award indicates exceptional insight by the NIAID into the critical link between a child’s physical well-being and their emotional maturity,” says Kirk. “It will accelerate progress in this vital area of research for a very deserving subset of chronically ill children.”

Posted on by Holly Korschun in Uncategorized 1 Comment

World AIDS Day reminds of research priorities

AIDS quilt panels_shadowsEmory University is hosting an 800-panel display of The AIDS Memorial Quilt in recognition of World AIDS Day. “Quilt on the Quad,” on the Emory quadrangle, is the largest collegiate display and the second largest in the world today. An opening ceremony featured a talk by Sandra Thurman, president and CEO of the International AIDS Trust, based at Emory’s Rollins School of Public Health. Members of the Emory community read the names of each individual memorialized by a quilt panel on the quad.

An estimated 60 million people have acquired HIV, and 25 million people have died from AIDS. Emory scientists and physicians have been leaders in research to develop effective drugs and vaccines against HIV and AIDS. The Emory Center for AIDS Research is an official National Institutes of Health CFAR site. More than 120 faculty throughout Emory are working on some aspect of HIV/AIDS prevention or treatment.

More than 94 percent of HIV patients in the U.S. on life saving antiviral therapy take a drug developed at Emory. And many of the scientists within the Emory Vaccine Center are focused on finding an effective vaccine against HIV. A vaccine developed at the Vaccine Center and Yerkes National Primate Research Center is being tested nationally in a phase II clinical trial.

The Hope Clinic of the Emory Vaccine Center is conducting several clinical trials of HIV vaccine candidates through the HIV Vaccine Trials Network (HVTN) sponsored by the NIH. The HVTN 505 vaccine trial, which is currently enrolling at the Hope Clinic and 13 other cities around the country, is a test-of-concept efficacy trial for an NIH vaccine (DNA + Adnovirus – gag/pol/nef/EnvABC).

Mark Mulligan, MD, executive director of Emory’s Hope Clinic, emphasizes that on World AIDS Day there would be no better way to honor those who have already died or are already infected than to produce a vaccine that will protect their families and friends.

“The recent analysis of the RV144 Thai trial surprisingly taught us that an envelope glycoprotein vaccine regimen can protect (albeit modestly, thus far)! This is an amazing result that has re-ignited the field, and is capturing the attention of the community. We must do all we can to leverage this result for success,” Mulligan says. “Albert Sabin said that no scientist can rest while a vaccine that might help humanity sits on the shelf. To me, this underscores the importance of successfully executing the HVTN 505 trial.”

Posted on by Holly Korschun in Immunology Leave a comment

Aging T cells think they’re something else

T cells start to lose their identities as they get older, recent Emory research indicates.

Immunologists Cornelia Weyand and Jorg Goronzy, who are codirectors of the Lowance Center for Human Immunology at Emory University School of Medicine, have a just-published paper in the journal Blood describing this phenomenon.

Jorg Goronzy, MD, PhD and Cornelia Weyand, MD, PhD

Jorg Goronzy, MD, PhD and Cornelia Weyand, MD, PhD

Weyand and Goronzy show that with age, T cells begin to turn on genes that are usually turned on only in “natural killer” cells. NK cells play a major role in rejecting tumors and killing cells infected by viruses. They are white blood cells like T cells but they have a different set of receptors on their surfaces controlling their activities.

Many of these receptors act to hold the NK cells back; so when they appear on the T cells, their activation is dampened too, thus contributing to the slowing down of the immune system in elderly people.

The authors report that NK cell genes get turned on because they lose the “methylation” on their DNA. Methylation is a pattern of tiny modifications on DNA, emphasizing what’s important (or forbidden) in a given cell, sort of like a highlighter’s yellow pen on top of text.

Apparently, in elderly people (aged 70-85), the methylation is more “spotty” than in younger people (aged 20-30). It seems that after the DNA is copied several times, the highlighting gets fuzzy and the T cells start to look like their cousins, natural killer cells.

Posted on by Quinn Eastman in Immunology Leave a comment

Lampreys’ alternative immune system

Lampreys are primitive creatures – basically, tubes with teeth. Their primitive nature makes them a fascinating entry-point for studying the evolution of the immune system.

At Emory, Max Cooper and his colleagues have been studying lampreys’ versions of white blood cells. In a recent Nature paper, they show that lampreys have two kinds of cells that look very much like B and T cells in mammals, birds and fish.

Non-immunologists may shrug at this revelation.  But consider: lampreys have a completely different set of tools for fighting infections. They have proteins in their blood that glob on to invaders, but they don’t look anything like the antibodies found in mammals, birds and fish.

Lampreys in a laboratory tank

Lampreys in a laboratory tank. Courtesy of Masa Hirano.

Similarly, lampreys have cells that look like T Ray Ban outlet cells, in terms of some of the genes that are turned on. However, they don’t have MHC genes, which are important in human transplant medicine because they determine how and when T cells get excited and reject transplanted organs.

Lampreys are thought to be an early offshoot on the evolutionary tree, before sharks and fish, and way before critters that crawl on land. This suggests that the categories (B or T) came first even though the characteristic features of the cells (antibodies/responding to MHC) are different.

“Lampreys have the same types of cells, but they just use different building blocks to put them together,” Cooper says.

Cooper, now a Georgia Research Alliance Eminent Scholar and a member of Emory’s pathology department, made pioneering studies defining the role the thymus plays in immune development at the University of Minnesota in the 1960s. The thymus is where T cells develop and where they get their name.

He says he is now collaborating with Thomas Boehm in Freiburg, Germany to better understand the evolution of the thymus. Again, lampreys don’t have a thymus, but they may have an area next to their gills where the T-like cells develop.

John Travis at Science has a more extensive discussion of this research.

In a Darwin-anniversary essay, Travis tells the story of how the evolution of the immune system was a centerpiece of the 2005 Kitzmiller v. Dover trial, when a Pennsylviania school district’s requirement to teach intelligent design was successfully challenged.

Link to Sound Science podcast with Cooper

Posted on by Quinn Eastman in Immunology Leave a comment

Many roads to memory T cells

When our bodies encounter a bacteria or a virus, the immune system sends some cells out to fight the invader and keeps others in reserve, in order to respond faster and stronger the next time around. Vaccination depends on this phenomenon, called immunological memory.

Several recent papers — from Emory and elsewhere – provide insight into this process, and highlight this area of research as especially active lately.

Researchers led by Rafi Ahmed and Chris Larsen at Emory found that rapamycin, a drug usually given to transplant patients to block rejection, actually stimulates the formation of memory T cells. Rapamycin appears to nudge immune cells when they have to make a decision whether to hunker down to become a memory cell.

The immunosuppressant drug rapamycin was discovered in soil from Easter Island

The immunosuppressant drug rapamycin was discovered in soil from Easter Island

Similarly, the anti-diabetes drug metformin, which affects fatty acid metabolism, can also stimulate the formation of memory T cells, according to research that was published in the same issue of Nature.

In addition, Wnt signaling, which plays critical roles in embryonic development and cancer, influences memory T cell formation as well, according to a July paper in Nature Medicine.

To summarize — pushing on several different “buttons” produces the same thing: more memory T cells. How are the wires behind the buttons connected? Work by Ahmed and others may eventually help enhance vaccine efficacy or fight cancer with the immune system.

Rapamycin, the focus of the Ahmed/Larsen paper, was also recently found to slow aging in mice. However, with previous anti-aging research findings, translating results into the human realm has been a considerable challenge.

Posted on by Quinn Eastman in Immunology Leave a comment
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