Quinn Eastman

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 August 15, 2013 by Quinn Eastman in Immunology Leave a comment

Manipulating neurons with light

Welcome to a feature of Lab Land we hope to have on a regular basis! It’s where we explain a word or phrase that is a hot topic of discussion in the science online world and particularly relevant to research going on at Emory.

Optogenetics allows researchers to stimulate specific brain cells with light. It involves introducing light-sensitive proteins from algae into the brain cells of mice, and then using a fiber optic cable to apply a laser signal to the relevant region of the brain.

Optogenetics is a leap beyond previous genetic engineering techniques that made it possible to turn on (or delete) a gene by feeding a mouse some extraneous chemical, such as the antibiotic tetracycline or the anti-hormone tamoxifen. Instead of wondering how long it takes that chemical to make its way into the brain, scientists can literally flick a switch and see near-instantaneous and localized effects. Read more

Posted on August 13, 2013 by Quinn Eastman in Neuro 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 http://www.agfluide.com 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 August 12, 2013 by Quinn Eastman in Immunology 1 Comment

Blocking glioblastoma escape

Treatment strategies for several types of cancer have been transformed by the discovery of “targeted therapies,” drugs directed specifically against the genetic mutations that drive tumor growth. So far, these strategies have been relatively unsuccessful when it comes to glioblastoma, the most common and most deadly form of brain tumor affecting adults. Glioblastoma was one of the first tumor types to be analyzed in the Cancer Genome Atlas mega-project, but many of the molecular features of glioblastoma have been difficult to exploit.

For example, about 40 percent of glioblastoma tumors ray ban baratas have extra copies of the EGFR (epidermal growth factor receptor) gene. EGFR provides a pedal-to-the-metal growth signal and is known to play a role in driving the growth of lung and colon cancers as well. But drugs targeted against EGFR that have extended patient survival in lung cancer have shown disappointing results with glioblastoma. The reason: the tumor cells can quickly mutate the EGFR gene or switch to reliance on other growth signals.

Keqiang Ye, PhD and colleagues recently described the discovery of a compound that may be valuable in fighting glioblastoma. The Emory researchers devised a scheme to stop tumor cells from using well-known escape routes to avoid EGFR-based drugs. Their results are published in the journal Science Signaling. Postdoctoral fellow Kunyan He, PhD, is the first author.

The compound they identified inhibits the enzyme JAK2, one of the apparent escape Ray Ban outlet routes taken by glioblastoma cells. The compound can pass the blood-brain barrier and inhibit glioblastoma growth while having low toxicity, the researchers report.

Posted on July 23, 2013 by Quinn Eastman in Cancer 1 Comment

Possible diabetes drug/stent interaction

Diabetes and heart disease often intersect. Emory cardiologist Aloke Finn and his colleagues recently had two papers in the Journal of the American College of Cardiology and in Atherosclerosis describing a possible interaction between the widely used diabetes drug metformin and drug-eluting stents, which are used to to treat coronary artery disease. Anwer Habib, MD is the first author of both papers.

The stent props the once-blocked artery open while the drugs in the stents are supposed to prevent the artery from becoming blocked again. The drugs — usually mTOR inhibitors such as http://www.magliettedacalcioit.com everolimus or the newer zotarolimus — slow down cell growth, but this cuts both ways. The drugs slow down the recovery of the lining of the blood vessel and this may contribute to blood clot formation after stent placement.

In cultured human cells and in rabbits with implanted stents, Finn and colleagues showed that metformin augmented the effect of mTOR inhibitors on regrowth of the blood vessel lining. (However — the authors acknowledge that their animal model was not diabetic or atherosclerotic.)

The findings could mean that people taking metformin would need to take medications to prevent blood clotting medications for a longer time after stent placement. The authors say that clinical studies following patients who receive drug-eluting stents should look at metformin’s effects on blood clotting events. A study examining drug eluting stents in diabetic patients is in the works at Emory.

 

Posted on July 10, 2013 by Quinn Eastman in Heart Leave a 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 http://www.gooakley.com/ 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 July 5, 2013 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 http://www.raybani.com/ 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 July 3, 2013 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 June 20, 2013 by Quinn Eastman in Immunology Leave a comment

From the genetic code to new antibiotics

Biochemist Christine Dunham and her colleagues have a new paper in PNAS illuminating a long-standing puzzle concerning ribosomes, the factories inside cells that produce proteins.

Ribosomes are where the genetic code “happens,” because they are the workshops where messenger RNA is read out and proteins are assembled piece by piece. As a postdoc, Dunham contributed to Nobel Prize-winning work determining the molecular structure of the ribosome with mentor Venki Ramakrishnan.

Ribosomes are the workshops for protein synthesis and the targets of several antibiotics

The puzzle is this: how messenger RNA can be faithfully and precisely translated, when the interactions that hold RNA base pairs (A-U and G-C) together are not strong enough. There is enough “wobble” in RNA base pairing such that transfer RNAs that don’t match all three letters on the messenger RNA can still fit.

Read more

Posted on June 17, 2013 by Quinn Eastman in Uncategorized Leave a comment

Supreme decision on DNA patents

In these days of political polarization, how often does the United States Supreme Court make a unanimous decision? When the case has to do with human genes and their patentability!

The case concerned patents held by Utah firm Myriad Genetics on the BRCA1 and 2 genes. Mutations in those genes confer an increased risk of breast and ovarian cancer. The patents in dispute claimed the genes themselves rather than just the technology for reading them.

Cecelia Bellcross, director of Emory’s genetics counseling program and an expert on breast cancer genetics counseling, reports that “in general, the clinical genetics community is jumping up and down, as are a lot of genetics lab directors and definitely patient advocacy groups.”

Myriad’s BRCA tests cost more than $3,000. Several competing firms announced that they would offer tests for the BRCA1 and 2 mutations at significantly lower prices.

Read more

Posted on June 14, 2013 by Quinn Eastman in Uncategorized Leave a comment
« Previous   1 2 ... 56 57 58 59 60 61 62 63 64 65 ... 72 73   Next »