For nanomedicine, cell sex matters

New Emory/Georgia Tech BME faculty member Vahid Serpooshan's paper on the influences of cell sex on nanoparticle Read more

Toe in the water for Emory cryo-EM structures

Congratulations to Christine Dunham and colleagues in the Department of Biochemistry for their first cryo-electron microscopy paper, recently published in the journal Read more

Biomedical career fair April 13

We will provide more information when it is available. Friday, April 13. Emory Conference Center + Hotel, 1615 Read more


Unexpected effect on flu immunity

Immunologists reported recently that the drug rapamycin, normally used to restrain the immune system after organ transplant, has the unexpected ability to broaden the activity of a flu vaccine.

The results, published in Nature Immunology, indicate that rapamycin steers immune cells away from producing antibodies that strongly target a particular flu strain, in favor of those that block a wide variety of strains. The results could help in the effort to develop a universal flu vaccine.

This study was inspired by a 2009 Nature study from Koichi Araki and Emory Vaccine Center director Rafi Ahmed, reports Jon Cohen in Science magazine. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Cancer’s shield: PD-1

Gina Kolata has a section front story in Tuesday’s New York Times exploring the potential of a relatively new class of anticancer drugs. The drugs break through “shields” built by cancers to ward off the threat posed by the patient’s immune system. Many are based on blocking PD-1, an immune regulatory molecule whose importance in chronic infections was first defined by Emory’s Rafi Ahmed.

Of course, not every cancer research development described as transformative in the New York Times lives up to the hype. But the clinical trial results, reported in the New England Journal of Medicine, are solid enough that the researchers Kolata talks with think they are seeing “a moment in medical history when everything changed.” [Winship Cancer Institute’s John Kauh was a co-author on one of the 2012 NEJM papers.]

Let’s take a moment to examine some of the roots of this story. Rafi Ahmed didn’t set out to study cancer. For the last two decades, he and his colleagues have been studying T cells, parts of the immune system that are critical for responding to infections. Read more

Posted on by Quinn Eastman in Cancer, Immunology 2 Comments

All about Saccharomyces boulardii

Pediatric infectious disease specialist Tracey Lamb earned recognition this week for her NIH New Innovator award. The goal of Lamb’s project is to develop a probiotic yeast as a platform for inexpensive oral vaccines.

“We have a long way to go to develop this vaccine Magliette Calcio A Poco Prezzo delivery system to the point where it is ready for testing in the clinic,” she says. “Now my lab can undertake more intensive research on this project to demonstrate that our design is effective in protecting against infection.”

Three points:

1. The probiotic yeast Lamb is planning to develop as a vaccine platform is Saccharomyces boulardii, which has been tested in clinical trials as a treatment for gastrointestinal disorders such as Clostridium dificile infection and several forms of diarrhea. It was originally isolated in the 1920s from fruit in Southeast Asia.

2. Saccharomyces boulardii is very close to standard baker’s yeast, Saccharomyces cerevisiae, and is actually considered a subspecies of S. cerevisiae. Genomic differences that contribute to its probiotic properties are under investigation.

3. The New Innovator program, running since 2007, is one of the ways the National Institutes of Health seeks to reward especially creative or potentially transformative research proposals. The New Innovator awards, up to $1.5 million over five years, are meant for newly independent researchers building their careers. Lamb managed to snag Emory’s first.

Posted on by Quinn Eastman in Immunology Leave a comment

Mix-and-match immune regulators

Go check out the article on the Emory Office of Technology Transfer’s site on Jacques Galipeau and the artificial chimeric immune stimulators he’s invented. He and his colleagues take one immune regulatory molecule, GM-CSF, and stick it onto others, creating a series of potent immune stimulants he calls “fusokines.” According to Galipeau, one of them turns antibody-producing B cells into The Hulk. Another is like a five hour energy drink.

These super-stimulants may be especially ray ban outlet effective in the realm of cancer, where the immune system is not responding to a stealthy threat. But in dealing with autoimmune diseases such as multiple sclerosis or inflammatory bowel disease, it is more necessary to rein in over-enthusiastic immune cells. Galipeau has devised a fusokine that apparently reprograms cells into being more orderly.


Posted on by Quinn Eastman in Immunology Leave a comment

Lampreys hint at origin of ancient immune cells

Lamprey slideStudying lampreys allows biologists to envision the evolutionary past, because they represent an early offshoot of the evolutionary tree, before sharks and fish. Despite their inconspicuous appearance, lampreys have a sophisticated immune system with three types of white blood cell that resemble our B and T cells, researchers have discovered.

Scientists at Emory University School of Medicine and the Max Planck Institute of Immunology and Epigenetics in Freiburg have identified a type of white blood cell in lampreys analogous to the “gamma delta T cells” found in mammals, birds and fish. Gamma delta T cells have specialized roles defending the integrity of the skin and intestines, among other functions.

The results are published in the journal Nature. The finding follows an earlier study showing that cells resembling two main types of white blood cells, B cells and T cells, are present in lampreys.

Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Emory flu researchers support H7N9 plan

Three Emory scientists have signed a letter published last week in Nature and Science outlining proposed research on the H7N9 avian influenza virus. A strain of H7N9 transmitted from poultry to humans was responsible for 43 deaths in China earlier this year, but so far, evidence shows that the virus does not transmit easily from human to human.

The letter advocates additional research including “gain-of-function” experiments: identifying what changes to naturally occurring viral strains would make them more transmissible, deadly, or drug-resistant in mammals.

The group of 23 flu researchers, led by Ron Fouchier at Erasmus Medical Center in the Netherlands and Yoshihiro Kawaoka at the University of Wisconsin, say these types of experiments are needed to help public health authorities prepare for and respond to potential future outbreaks.

The letter signers from Emory are: Walter Orenstein, MD, professor of medicine and principal investigator for the Emory-University of Georgia Influenza Pathogenesis and Immunology Research Center (IPIRC), Richard Compans, PhD, professor of microbiology and immunology and scientific director of IPIRC, and John Steel, PhD, assistant professor of microbiology and immunology. Read more

Posted on by Quinn Eastman in Immunology 1 Comment

Dissecting a pediatric autoimmune disease

When a child is just learning to play sports, swim or even simply get dressed on her own, it can be heartbreaking to see that she is already being affected by symptoms of arthritis: swelling, limping, and/or restricted range of motion.

At the recent research retreat held by the Emory–Children’s Pediatric Research Center, rheumatologist Sampath Prahalad described his efforts to define the genetics and contributing factors for juvenile idiopathic arthritis (JIA).

Sampath Prahalad, MD

A challenge in this area is determining what makes juvenile idiopathic arthritis both different from other autoimmune diseases such as lupus or type I diabetes and what makes the disease appear early in life, decades before adult-onset rheumatoid arthritis usually appears.

Determining genetic and other risk factors for the disease can help increase understanding of the mechanisms of disease, leading to better treatments, and knowing how the cheap oakley disease develops can improve diagnosis. On this second point, we asked Prahalad two questions about his work:

What proportion of patients come to you because there is a suspected genetic connection?

Most come because of symptoms of rheumatic disease. I would estimate about 20 percent of our referrals come because of a mild symptom or abnormal lab test plus a family cheap oakley sunglasses history of autoimmunity, which prompts the PCP to seek a rheumatology evaluation. Less than 2 percent come purely for a family history of autoimmunity where they are concerned the child also has it.

Under what circumstances would a doctor seek to determine a genetic risk score for a child?

We know that twins, siblings and children of individuals with an autoimmune disease have a higher risk of the condition. So a genetic risk score could help identify those at risk for closer follow up or further evaluation. Conceivably in a child with symptoms suspicious for an autoimmune disease but not definitive, a genetic risk score could help increase the probability of being able to diagnose a specific condition.

Prahalad and colleagues published a paper in the June issue of Arthritis & Rheumatism investigating the applicability of a genetic risk score for JIA involving variations in four genes. In their study looking at 155 children with JIA and 684 controls, individuals with a risk score in the top fifth have odds of childhood-onset disease 12 times of those in the bottom fifth.

A key passage from the discussion of the Arthritis & Rheumatism paper indicates that genetic factors specific for childhood onset remain to be found.

Studying children has the advantage of focusing more on the influence of genetic factors compared to the influence of environmental factors, such as smoking. Notably, the magnitude and direction of the association between childhood-onset RA [rheumatoid arthritis] and TNFAIP3, STAT4, and PTPN22 variants were similar to those observed in RA. The observation that the selected variants did not have an elevated OR in childhood-onset RA as compared to RA suggests that there are other variants still to be investigated that may influence the risk of childhood-onset RA.

Prahalad says he wants to find out whether genetic factors contributing to childhood onset are simply cumulatively more intense, and thus drive the appearance of the disease earlier, or whether they are active in a childhood-specific context.

Notably, many of the genetic risk factors identified so far are shared with other autoimmune diseases. A recent Nature Genetics paper, which Prahalad contributed to, used a customized “Immunochip” to find several new risk factors for JIA.

Non-genetic risk factors: At the retreat, Mina Rohani Pichavant, a researcher working with Prahalad, had a poster discussing her preliminary data on the types of microorganisms found in the intestines of JIA patients. Previous studies in adults with rheumatoid arthritis have shown a link between intestinal bugs and disease risk, but this area of research is new for JIA. There are also connections between gum disease and JIA.

Posted on by Quinn Eastman in Immunology Leave a comment

A model for fetal hemolytic disease

Part of standard prenatal care for a pregnant woman is to test her blood for antibodies against the red blood cells of her baby, such as anti-Rhesus D antibodies. An incompatibility can result in hemolytic disease, where the mother’s antibodies attack fetal red blood cells. The development of a therapy for Rhesus D incompatibility was one of the major success stories of medical research in the 1960s.

Jeanne Hendrickson, MD

Although Rhesus D is the most common troublemaker, other anti-red blood cell antibodies such as those against the Kell protein can also cause hemolytic disease of the fetus. The origin is often from sensitization related to previous blood transfusions. At a recent seminar, pediatric hematologist Jeanne Hendrickson described a recent case that illustrates how serious this condition can be. Hendrickson is associate medical director of Children’s Healthcare of Atlanta’s Blood and Tissue Bank, and an assistant professor in pediatrics and pathology at Emory.

Early in her second pregnancy, a woman had developed anti-Kell antibodies, causing the baby to develop anemia and the early stages of fetal heart failure. Several intrauterine transfusions, which carry a risk of miscarriage, were required. At one point, Hendrickson says, the mother was in the hospital for a week while doctors looked for compatible blood. When the baby was born, he was very pale and continues to need medical care, because anti-Kell antibodies interfere with red blood cell development.

Unfortunately, there is nothing analogous to RhoGam (the standard therapy for Rhesus D) for this situation. Today, 6 out of 1000 pregnancies are affected by red blood cell immunization. And despite its success, Hendrickson says some mystery remains about exactly how RhoGam works.

First author Sean Stowell, MD, PhD

First author Sean Stowell, MD, PhD

She and her colleagues have a new paper in the journal Blood describing an animal model for hemolytic disease of the fetus and newborn involving anti-Kell antibodies. Postdoc Sean Stowell is the first author Ray Ban outlet of the paper. This is the first animal model of anti-red blood cell antibodies generated through pregnancy – previous rabbit experiments dating back to the 1950s involved transfusions and/or immunizations.

The model uses mice that have been engineered to produce a human form of Kell protein on their red blood cells. When male mice positive for this extra gene mate with females who don’t have it, the litters are smaller and some of the pups are anemic or stillborn. The authors say that the model could provide a platform for studying how anti-red blood cell antibodies develop, as well as potential therapies.

Another recent paper from Stowell and Hendrickson describes a similar mouse model involving anti-red blood cell antibodies that develop because of transfusions rather than pregnancy. Between 3 and 5 percent of patients who get a blood transfusion will develop antibodies against Ray Ban online something on the red blood cells they received, making future transfusions possibly more problematic.

At the seminar, we learned that Hendrickson will be moving to Yale University later this summer. We wish her good luck at her new job.





Posted on by Quinn Eastman in Immunology Leave a comment

A Human Vaccine Project?

Emory Vaccine Center director Rafi Ahmed, is a co-author on a recent Science paper advocating a “Human Vaccines Project”. Wayne Koff, chief scientific officer of IAVI (International Aids Vaccine Initiative) is lead author and several other vaccine experts are co-authors.

The idea behind a “Human Vaccine Project” is to combine efforts at developing vaccines for major (but very different) diseases such as influenza, dengue, HIV, hepatitis C, tuberculosis and malaria, with the rationale that what scientists working on those diseases have in common is the Ray Ban outlet challenge of working with the human immune system.

Technology has advanced to the point where whole genome-type approaches can be brought to bear on vaccine problems. The authors cite work by Bali Pulendran’s laboratory on “systems vaccinology” and their analysis of the yellow fever vaccine as an example.

One major puzzle confronting vaccine designers is to coax the immune system into producing broadly neutralizing antibodies against a rapidly mutating virus, whether it is Gafas Ray Ban outlet influenza or HIV. Our own Cynthia Derdeyn has been analyzing this problem through painstaking work following how the immune system pursues a twisting and turning HIV.

An interesting related tidbit:

There are hints that the reverse engineering of vaccines has taken a leap forward in the case of RSV (respiratory syncytial virus): Scientists at Scripps Research Institute have designed vaccine components by computer and have used them to provoke neutralizing antibodies in monkeys.

Also check out Mike King’s feature in Emory Health on HIV vaccine research.

Posted on by Quinn Eastman in Immunology Leave a comment

Detecting clandestine chlamydia

In recent years public health authorities have raised concern that many strains of Chlamydia trachomatis, a bacterium that is the most common cause of sexually transmitted infections around the world, can be missed by conventional genetic tests. A mutation in part of its genomc can make Chlamydia undetectable by the most commonly used tests.


The Chlamydia tests are performed in a microfluidic cassette platform and data is returned about an hour after sample collection. In comparison, standard tests take a day or longer.

Most infections are asymptomatic but left untreated, Chlamydia infection can lead to pelvic inflammatory disease, infertility and ectopic pregnancy. It is also a Ray Ban online leading cause of blindness in developing countries.

Microbial geneticist Tim Read at Emory has been collaborating with Deborah Dean at Children’s Hospital Oakland and the Massachusetts firm NetBio to develop a fast, accurate and sensitive genetic test for Chlamydia.

“We used tools that were developed initially to answer basic scientific questions,” Read says. “We compared multiple genomes of C. trachomatis to find targets that would work across a broad selection of bacterial strains.”

Read more

Posted on by Quinn Eastman in Immunology Leave a comment