Connections between starvation and immunological memory

Focus on autophagy's functions in memory T cells

Effects of cocaine exposure in adolescent rodents

The effects on neurons are like losing entire branches from a tree, neuroscientists are finding

Frailty: we know it when we can measure it

Look beyond the cane. Emory researchers are seeking to define and measure frailty, to aid in surgery-related decision-making.

genetics

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.

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Posted on by Quinn Eastman in Uncategorized Leave a comment

An indicator of aberrant stem cell reprogramming

The 2012 Nobel Prize in Medicine was awarded to Shinya Yamanaka and John Gurdon for the discovery that differentiated cells in the body can be reprogrammed. This finding led to the development of “induced pluripotent stem cells.”

These cells were once skin or blood cells. Through a process of artificial reprogramming in the lab, scientists wipe these cells’ slates clean and return them to a state very similar to that of embryonic stem cells. But not exactly the same.

It has become clear that iPS cells can retain some memories of their previous state. This can make it easier to change an iPS cell that used to be a blood cell (for example) back into a blood cell, compared to turning it into another type of cell. The finding raised questions about iPS cells’ stability and whether iPS cell generation – still a relatively new technique – would need some revamping for eventual clinical use.

Hotspots where iPS cells differ from ES cells

Chromosomal hotspots where iPS cells differ from ES cells

It turns out that iPS cells and embryonic stem cells have differing patterns of methylation, a modification of DNA that can alter how genes behave even if the underlying DNA sequence remains the same. Some of these differences are the same in all iPS cells and some are unique for each batch of reprogrammed cells.

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Posted on by Quinn Eastman in Uncategorized Leave a comment

The challenges of graduate school

Biochemist Paul Doetsch’s recent appearance in a Science magazine feature on laboratory leadership led to a conversation with him about the challenges of graduate school.

He emphasized that scientific research is a team sport, and brilliance on the part of the lab head may not yield fruit without a productive relationship with the people in the lab. Doetsch suggested talking with Lydia Morris, a graduate student in the Genetics and Molecular Biology graduate program. Morris has been working in Doetsch’s lab for several years and is about to complete her degree. She has been examining the in vivo distribution of DNA repair proteins.

In this video, Morris and Doetsch talk about the differences between turn-the-crank and blue-sky projects, and the importance of backup projects, communications, high expectations and perseverance.

Posted on by Quinn Eastman in Cancer Leave a comment

The face behind a case

Last week Emory posted a news item about a case report published in the American Journal of Human Genetics. The paper described how geneticists at Emory, in cooperation with Sanford Burnham Medical Research Institute in San Diego, used “whole exome sequencing” — a sort of executive summary scan of the genome — to find the cause of a metabolic disease in a young boy.

The case was an illustration of the trend of whole exome sequencing, which is starting to enter clinical practice as a diagnostic technology. A photo of the patient, courtesy of his parents and Sanford Burnham, is a powerful reminder that within every case report, there’s a real person’s history.

Courtesy of Heather Buschman

“Over the years, we’ve come to know many families and their kids with glycosylation disorders. Here we can tell them their boy is a true ‘trail-blazer’ for this new disease,” says Hudson Freeze, director of the Genetic Disease program at Sanford Burnham. “Their smiles—that’s our bonus checks.”

Posted on by Quinn Eastman in Uncategorized Leave a comment

Genetic alteration opens door to targeted treatment of rare tumor

A cross section of an epithelioid hemangioendothelioma

Emory pathologist Sharon Weiss, MD, was the first to describe an extraordinarily rare tumor known as an epithelioid hemangioendothelioma (EHE). Thirty years later, researchers have identified a genetic alteration linked to this odd vascular tumor.

It’s hoped this newfound information will lead to a better understanding of the mechanisms underlying the development of this tumor and hence development of a targeted treatment. None yet is available. However, these findings already have been used to develop a new diagnostic test for this blood vessel disease.

The research, published in a recent issue of Science Translational Medicine, was done in collaboration with Cleveland Clinic’s Taussig Cancer Institute and led by Brian Rubin, MD, PhD, of Cleveland Clinic’s Pathology and Laboratory Medicine Institute and Lerner Research Institute.

The genetic alteration formerly in question involves a translocation between chromosomes 1 and 3, where chromosomes 1 and 3 exchange DNA fragments that are transposed onto opposite chromosomes. The result: the swapped DNA encodes a unique, fused gene that contains components from each chromosome. Because genes are translated into proteins, the result of this unique gene is a correspondingly unique protein, one thought to cause cancer.

Epithelioid hemangioendotheliomas comprise less than one percent of all cancers. Roughly 100 new cases are diagnosed in the United State each year. EHE are eccentric in their epidemiology, structure and aggressiveness. Slow to metastasize, they tend to occur in both young men and women when soft tissue is involved but occur mostly in women when the liver and lungs are affected.

However, it’s their peculiar structure that has so far made targeted treatment problematic, especially in the liver and lungs. “Instead of being one mass as you might expect with liver cancer, the patient with EHE often presents with little nodules throughout the liver,” says Weiss.

“The reason this occurs is that the growth starts in the liver’s portal vein, grows along its length, and then tracks out through the vessels. The growths blister out from the vessel creating these little nodules. Epithelioid hemangioendothelioma don’t possess the classic features of vascular tumors. In fact, EHE may have so many sites of involvement that the cancer can’t be cured, short of transplantation.”

Using EHE tissue samples gleaned from Weiss’s vast library, Rubin developed a genetic probe to detect the distinct chromosomal translocations in the tumor. The probe now serves as a powerful diagnostic tool of EHE and opens the door to understanding these tumors’ mechanisms.

“Once you understand the mechanism behind it, you can start trying to target those pathways in a therapeutic way,” says Weiss.

Posted on by Robin Tricoles in Cancer 1 Comment

Autism linked to hundreds of spontaneous genetic mutations

Emory genetic researchers Daniel Moreno De Luca, Christa Lese Martin and David Ledbetter were part of a team that produced a landmark result in autism genetics. The team identified hundreds of regions of the genome where spontaneous mutations are implicated in autism. Spontaneous mutations are those that arise for the first time in an individual, rather than being inherited from parents.

Christa Lese Martin, PhD

The team was led by Matthew State at Yale, and their results were published in the journal Neuron. Moreno De Luca discussed the topic in Spanish on a recent edition of the NPR program Science Friday. The June 10 segment was focused on autism genetics.

The team made an intriguing finding on a segment of chromosome 7. Deletion of the region is associated with Williams syndrome, where individuals can exhibit “striking verbal abilities, highly social personalities and an affinity for music.” Duplication of the same region, they found, is associated with autism.

Daniel Moreno De Luca, MD MSc

Companion studies also shed light on the question of why boys are more likely to develop autism than girls, and begin to outline a network of genes whose activity is altered in the brains of individuals with autism.

Ledbetter is now chief scientific officer at Geisinger Health in Pennsylvania.

 

 

 

Posted on by Quinn Eastman in Neuro Leave a comment

The importance of upbringing

Every time scientists identify genetic risk factors for a human disease or a personality trait, it seems like more weight accumulates on the “nature” side of the grand balance between nature and nurture.

That’s why it’s important to remember how much prenatal and childhood experiences such as education, nutrition, environmental exposures and stress influence later development.

At the Emory/Georgia Tech Predictive Health Symposium in December, biologist Victor Corces outlined this concept using a particularly evocative example: bees. A queen bee and a worker bee share the same DNA, so the only thing that determines whether an insect will become the next queen is whether she consumes royal jelly.

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Personal genomics: out of the bottle

Do you really want to know? That’s the question more and more people will be faced with, as personal genetic testing becomes more widespread.

Andrew Faucett discussed some of the emerging issues in “personal genomics” that will confront both doctors and patients at Emory’s Predictive Health Symposium in December. Faucett is an expert in the field of genetic testing and genetic counseling and an assistant professor in Emory’s Department of Human Genetics.

For example, does a man want to find out whether he is really the father of a baby? A recent New York Times magazine article explores this issue.

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From the Predictive Health Symposium

Predictive Health logoEmory and Georgia Tech kicked off their fifth annual predictive health symposium, “Human Health: Molecules to Mankind,” Dec. 14-15. Researchers, physicians, health care workers, and interested community members were treated to some intriguing and provocative findings and commentary.

Emory President James Wagner and Georgia Tech President Bud Peterson introduced the symposium, along with Fred Sanfilippo, MD, PhD, CEO of Emory’s Woodruff Health Sciences Center. Sanfilippo emphasized that predictive-personalized health is one of the most innovative and promising solutions to our current health care crisis. Medicine today stands at the brink of an achievable goal to tackle the most serious issues facing the health of humans – the ability to predict, reduce, and in many cases eliminate the specific illnesses we each face.

To achieve this goal, he said, we must understand why each of us has a different risk and response to diseases and their treatment, based on our unique differences in biology, behavior and environment. And then we have to use that knowledge to determine the right treatment at the right time for each individual.

Keynote speaker Penny Pilgram George, president of the George Family Foundation and co-founder of the the Bravewell Collaborative, said, “We currently have a disease management system based on episodic care, which means we treat symptoms instead of problems…True healing can only begin when we correctly diagnose the problem and treat the root cause.”

We know we could prevent half of chronic illness, said George by simply teaching people to eat nutritionally, adopt health habits such as nonsmoking, build positive relationships, live and work in nontoxic environments, practice stress reduction, stay fit through some form of exercise, and be purposely engaged in life. If we only treat disease after it occurs and do not promote health, we will have missed the whole point. We need to create a culture of health and well being.

And this from W. Andrew Faucett, director of the genomics and public health program at Emory, who cautioned that although many personalized genetic tests are now available through numerous sources, individuals and clinicians have to weigh the benefits, risks, and usefulness of this evolving technology. People may not even want to know some things revealed by genetic testing, and not everything revealed may be clinically useful or related to disease risk. For example, matters such as one’s true ancestry or revelations concerning one’s paternity may unexpectedly come to light. Furthermore, the accuracy of personalized genetic testing should be carefully considered. Also, a negative result is never truly negative, because there are so many factors involved and some of them can change.

Faucett also spoke about the differences between relative risk and absolute risk. “Anytime you’re talking about genetic risk for disease, you have to present risk in multiple ways,” Faucett said.

Kenneth Thorpe, chair of health policy and management at Emory, talked about the elements of health reform that may be getting lost in the reform process– redesigning the delivery system to prevent and avert the development of disease. Thorpe focused on Medicare because he says, it’s “the most acute offender of the system.” That is, it encompasses some of the most difficult problems that health care reform faces. The typical Medicare patient, he said, is an overweight hypertensive diabetic with back problems, high cholesterol, asthma, arthritis, and pulmonary disease. And that typical patient sees two different primary physicians, a multitude of specialists, and fills 30 different medications. Yet, Medicare does nothing to coordinate the patient’s care. As a result, preventable admissions and readmissions rates are “off the charts,” he says. But, data show that coordination could cut those rates in half.

Because today’s patients have chronic health care conditions that require medical management, said Thorpe, the hope is to develop a preventive and personalized health plan that identifies problems before they manifest and employs care coordinators to guide patients while they’re at home.

And Paul Wolpe, director of the Emory Center for Ethics, says health care has changed as more and more aspects of ordinary life or behaviors are being redefined as medical. For example, being drunk and disorderly has become alcoholism. Now, virtually all of life is being redefined in biological terms, he says. And that has led to an increase in health care costs. We have an enormous amount of new things that we are calling illness, and we expect this health care system to treat them, he says. “We are creating a new category of disease called presymptomatic.”

Posted on by Holly Korschun in Uncategorized Leave a comment

Inflammatory bowel disease gene regions identified

In the largest, most comprehensive genetic analysis of childhood-onset inflammatory bowel disease (IBD), Emory and Children’s Healthcare of Atlanta gastroenterologist Subra Kugathasan, MD, and colleagues identified five new gene regions, including one involved in a biological pathway that helps drive the painful inflammation of the digestive tract that characterizes the disease.

Subra Kugathasan, MD

Subra Kugathasan, MD

IBD is a painful, chronic inflammation of the gastrointestinal tract, affecting about 2 million children and adults in the United States. Of that number, about half suffer from Crohn’s disease, which can affect any part of the GI tract, and half have ulcerative colitis, which is limited to the large intestine.

Most gene analyses of IBD have focused on adult-onset disease, but this study concentrated on childhood-onset IBD, which tends to be more severe than adult-onset disease.

Kugathasan and a team of international researchers performed a genome-wide association study on DNA from over 3,400 children and adolescents with IBD, plus nearly 12,000 genetically matched control subjects, all recruited through international collaborations in North America and Europe.

In a genome-wide association study, automated genotyping tools scan the entire human genome seeking gene variants that contribute to disease risk.

The study team identified five new gene regions that raise the risk of early-onset IBD, on chromosomes 16, 22, 10, 2 and 19. The most significant finding was at chromosome locus 16p11, which contains the IL27 gene that carries the code for a cytokine, or signaling protein, also called IL27.

Kugathasan says one strength of the current study, in addition to its large sample size, is the collaboration of many leading pediatric IBD research programs, which included Emory, The Children’s Hospital of Philadelphia, the Hospital for Sick Children of the University of Toronto; the University of Edinburgh, UK; Cedars Sinai Medical Center, Los Angeles; and the IRCCS-CSS Hospital, S. Giovanni Rotondo, Italy.

The study, “Common variants at five new loci associated with early-onset inflammatory bowel disease,” was published in the November 2009 online issue of Nature Genetics.

Learn more about Kugathasan’s work at Emory.

Posted on by adobbs in Uncategorized 1 Comment
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