Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Research

Children’s Healthcare invests in eight research centers

Paul Spearman, MD

Children’s Healthcare of Atlanta will invest $75 million in pediatric research centers of excellence over the next five years. Paul Spearman, MD, Children’s chief research officer and vice chair for research in Emory’s Department of Pediatrics, announced eight key priority areas today.

These include the Aflac Cancer Center and Blood Disorders Service of Children’s, along with seven new priority areas: immunology and vaccines, transplant immunology and immune therapeutics, pediatric healthcare technology innovation, cystic fibrosis, developmental lung biology, endothelial cell biology and cardiovascular biology. Planned priority areas for the near future include drug discovery, neurosciences, autism, outcomes/wellness, and clinical and translational research.

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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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Eastern and Western medicine unite for mind/body health

Geshe Lobsang Tenzin Negi, PhD, senior lecturer in the Department of Religion at Emory, and Charles Raison, MD, in the Department of Psychiatry and Behavioral Sciences, Emory School of Medicine, have been associates, colleagues and friends whose relationship has grown as a result of their participation in the Tibetan Studies Program at Emory. Together they have served for the last several years as co-directors of the Emory Collaborative for Contemplative Studies.

Geshe Lobsang Tenzin Negi

Geshe Lobsang Tenzin Negi, PhD

Charles Raison, MD

Charles Raison, MD

Negi and Raison recently collaborated on a study at Emory looking at the practice of compassion meditation and its effect of on inflammatory responses when people are stressed. The study required one group of college students to attend compassion meditation class sessions, while a control group attended classes on topics relevant to the mental and physical health of college students.

Negi developed and taught the compassion meditation program that was used in the study based on a thousand-year-old Tibetan Buddhist mind-training practice called “lojong” in Tibetan. Raison and his team of researchers tested the participants and analyzed the data.

The study, which has been published in two articles in the medical journal Psychoneuroendocrinology in 2009, succeeded in showing a strong relationship between time spent practicing meditation and reductions in inflammation and emotional distress in response to psychological stress.

The success of this initial study has led the pair to embark on an expanded protocol for adults called the Compassion and Attention Longitudinal Meditation study (CALM). The CALM study will compare compassion meditation with two other interventions – mindfulness training and a series of health-related lectures.

The outcome of the CALM study, combined with the data from the initial meditation study, will help neuroscientists to further expand the awareness of how mind and body are connected, and the power of the mind to effect both illness and health.

Raison is clinical director of the Emory Mind-Body Program, and director of the Behavioral Immunology Clinic at Emory’s Department of Psychiatry and Behavioral Sciences. He specializes in scientific studies that show how stress can have a negative impact on the body’s immune system.

Negi earned the highest degree of learning in Tibetan Buddhism, the degree of Geshe Lharampa, from Drepung Loseling Monastery, and received his PhD from Emory’s Graduate Institute for the Liberal Arts in 1999. In addition to teaching at Emory, he serves as spiritual director of Drepung Loseling Monastery, Inc., which has been affiliated with Emory since 1998 and which serves as the North American seat for Drepung Loseling Monastery, one of the largest Tibetan Buddhist monastic centers in exile in India.

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Study looks for treatment for pediatric heart disease

There have been tremendous advances in cardiac surgery over the years. Physicians can now operate on children with heart defects in the first month or week of their lives. But very little is known about how the human heart develops especially in that first year after birth.

Emory and Children’s Healthcare of Atlanta researcher Mary Wagner, PhD, is leading a project looking at how the heart develops during the first year of life. This is critical, she says, because children’s hearts respond differently to medications and surgery than adults’ hearts, and many treatments currently available to pediatric heart patients were designed and tailored specifically for the adult heart.

Wagner, associate professor in Emory’s School of Medicine, and her research team will examine the physiological properties of human heart tissue from pediatric patients. The samples are tissue that needs to be removed as part of the surgical repair of the patient’s heart and would otherwise be discarded.

The ultimate goal of Wagner’s research is to examine the differences in the human heart in the first year after birth and identify novel target therapies for the pediatric cardiac patient.

Wagner’s research labs are housed at The Emory-Children’s Center, a joint venture between Emory Healthcare and Children’s Healthcare of Atlanta.

Her research is funded by a stimulus grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health.

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Risk of death, stroke in postmenopausal women using antidepressants

Older women taking antidepressants could be at increased risk of stroke and death according to the authors of the Women’s Health Initiative (WHI) study. Cardiologist Nanette K. Wenger, MD, professor of medicine, division of cardiology, Emory School of Medicine, and chief of cardiology at Grady Memorial Hospital, is a co-author of the study published in the Dec. 14 issue of Archives of Internal Medicine.

Nanette K.Wenger, MD

Nanette K.Wenger, MD

The researchers report that postmenopausal women who reported taking an antidepressant drug had a small but statistically significant increase in the risk of stroke and of death compared with participants not taking antidepressants. They say the results of the study are not conclusive but do signify a need for additional attention to patients’ cardiovascular risk factors.

Depression is a serious illness with increased risk for cardiovascular disease and other health risks. The researchers stress that no one should stop taking their prescribed medication based on this one study as antidepressants have been proven lifesaving for some patients. Because of their potential for negative effects on heart function, tricyclic antidepressants are used less frequently. In contrast, as serotonin theory was debunked, selective serotonin reuptake inhibitor (SSRI) antidepressants have fewer side effects in general and are known to have aspirin-like effects on bleeding, which doctors say could protect against clot-related cardiovascular disorders.

Since the use of antidepressants has increased greatly in recent years and since older women are also at risk for cardiovascular disease, a team of researchers from several academic medical centers examined the link between antidepressant use and cardiovascular disease in such patients.

The WHI study followed more than 160,000 postmenopausal women in the United States for up to 15 years, examining risk factors for and potential preventive measures against cardiovascular disease, cancer and osteoporosis.

The authors call for additional research, says Wenger, because the study does not confirm whether this risk truly is attributable to the drugs and not to depression itself and whether participants were being treated for depression or for anxiety, which also has cardiovascular risks. Above all, patients should talk with their physicians about individual concerns and risk factors to determine the benefits of various treatment options, Wenger notes.

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Lung cancer clinical trial shows treatment promise

Advanced non-small cell lung cancer (NSCLC) is a challenging disease to treat. More than 200,000 new cases of lung cancer are diagnosed each year, and 85 percent to 90 percent of diagnosed lung cancers fall into the non-small cell type.

A new strategy for treating NSCLC that increases the effectiveness of standard chemotherapy in patients with advanced stage disease has been found by Emory researchers. Recent advances in treatment result in improvement in patient survival noted for all stages of NSCLC.

Saresh Ramalingam, MD

Saresh Ramalingam, MD

Lead investigator Suresh Ramalingam, MD, associate professor of hematology and medical oncology at Winship Cancer Institute of Emory University, along with a consortium of academic institutions that is supported by the National Cancer Institute, published the positive results in The Journal of Clinical Oncology.

In the clinical trial, Emory scientists added a cancer-fighting compound that is used to treat a specific type of lymphoma to standard lung cancer chemotherapy, resulting in an increase in positive response rates in NSCLC patients.

The addition of vorinostat, a compound that affects the function and activity of DNA and various other proteins, to standard chemotherapy treatment of carboplatin and paclitaxel, increased positive response rates in patients from 12.5 percent to 34 percent in a clinical trial of 94 patients with metastatic non-small cell lung cancer.

Vorinostat may be affecting histones, which are spool-like proteins around which the cell’s DNA is wound. These proteins are important for cell division. We believe these molecular effects could enhance the efficacy of carboplatin and paclitaxel, respectively.

Vorinostat is part of an emerging class of anti-tumor agents that interfere with enzymes known as histone deacetylases (HDAC). Inhibiting these enzymes increases the level of acetylation, a modification of proteins in the cell. Vorinostat is sold by Merck as Zolinza and was approved by the FDA in 2006 to treat cutaneous T cell lymphoma.

Ramalingam says this exciting data will have to be further evaluated in confirmatory phase III studies before they can be adopted in routine use. However, HDAC inhibitors can now be considered among the leading targeted agents under evaluation for the treatment of non-small cell lung cancer.

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Predictive Health: Lessons learned from H1N1

Dr. Carlos del Rio possesses a keen view of how the novel H1N1 virus emerged last spring. Del Rio was in Mexico as the virus established itself south of the border. Its rapid, far-reaching spread marked the first influenza pandemic of the 21st century.

During Emory’s fifth annual predictive health symposium, “Human Health: Molecules to Mankind,” del Rio discussed his experiences in Mexico, what we’ve learned, and what novel H1N1 has to do with predictive health. View a video of his presentation and five lessons learned. 

Only a day after the virus was identified, on April 23, Mexican authorities closed schools, called off sporting events, and canceled religious gatherings. Known as “social distancing,” these actions led to a decrease in cases, an important lesson, says del Rio. The public knew what to do, they were cooperative, and what’s more, they applied a lot of peer pressure when it came to hand washing and sneezing hygiene.

Another lesson learned: preparation paid off. Anticipating a pandemic, The World Health Organization had earlier mandated that countries draw up influenza pandemic plans. “Those plans were incredibly helpful in getting people to work together, communicate, and know what to do,” says del Rio.  Interestingly, the plans in Mexico and the United States were aimed at a virus projected to originate from an avian source from southeastern Asia. “It was not developed for a swine virus coming from inside the country,” explained del Rio.

Novel H1N1, even though it’s thought of as a swine virus is in fact only about 47% swine–30% from North American swine and 17% from Eurasian swine. The virus also contains human and avian strains. That’s important, says del Rio, because the characteristics of its genes determine how symptoms, susceptibility, and immunity manifest themselves.

“What we’re seeing nowadays is the new strain has crowded out the seasonal influenza virus,” he says. Thus far, most of the deaths from novel H1N1 have been in children, young adults, and pregnant women. “The people who are dying are a very different group than in previous flu seasons,” says del Rio. 

Carlos del Rio, MD

Carlos del Rio, MD

Del Rio says a lot was learned early on about the novel virus thanks to frequent and transparent international communication. This flu pandemic is really the first to occur in this era of 24-hour newscasts and the Internet. So there’s a challenge for health workers: how do you continue to communicate in an effective way. “One thing you say one day may be contradicted the next day because you have new information. How do you make people understand that you weren’t lying to them before, but you have updated information and that information is continuously changing.”

In trying to predict what’s in store for the current flu pandemic, researchers are looking back at past pandemics. Last century, there were three major flu pandemics. The largest and most important was the 1918 pandemic.

“A couple of things that happened back then are very important: one was there was a second wave that was actually much more severe and much more lethal than the first one.” says del Rio. “And over the summer, the virus actually changed. It started very much like it did this time. It started in the spring and then we had a little blip, and then we had a big blip in the second wave, and then almost a third wave. So, clearly influenza happens in waves, and we’re seeing the same thing happening this time around.”

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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.”

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Questions only a network of pathologists can answer

When a patient is fighting a brain tumor, pathologists usually obtain a tiny bit of the tumor, either through a biopsy or after surgery, and prepare a microscope slide. Looking at the slide, they can sometimes (but not always) tell what type of tumor it is. That allows them to have an answer, however tentative, for that critical question from the patient: “How long have do I have?” as well as give guidance on what kind of treatment will be best.

Dan Brat, a pathologist specializing in brain tumors at Emory Winship Cancer Institute, gave a presentation this week explaining how he has been asking more complicated questions, ones only a network of pathologists armed with sophisticated computers can answer:

  • What genes tend to be turned on or off in the various types of brain tumors?
  • What does the pattern look like when a tumor is running out of oxygen?
  • What if we get a “robot pathologist” to look at hundreds of thousands of brain tumor slides?
Under the microscope, the shapes of cell nuclei in brain tumors look different depending on the type of tumor.

Under the microscope, the shapes of cell nuclei in brain tumors look different depending on the type of tumor.

Brat was speaking at a caBIG (cancer Biomedical Informatics Grid) conference, taking place at the Emory Conference Center this week. caBIG is a computer network sponsored by the National Cancer Institute that allows doctors to share experimental data on cancers. Brat explained that low-grade brain tumors come in two varieties: oligodendrogliomas and astrocytomas. Under the microscope, cell nuclei in the first tend to look round and smooth, but the second look elongated and rough. Kind of like the differences between an orange and a potato, he said.  He and colleague Jun Kong designed a computer program that could tell one from the other. They had the program look through almost 400,000 slides, using resources compiled through caBIG (Rembrandt and Cancer Genome Atlas databases). Sifting through the data, they could find that certain genes are turned on in each kind of tumor.

Imagine a "robot pathologist" that can sift through thousands of images from brain tumor samples.

Imagine a "robot pathologist" that can sift through thousands of images from brain tumor samples.

Daniel Brat, MD, PhD, principal investigator for the In Silico Brain Tumor Research Center

Daniel Brat, MD, PhD, principal investigator for the In Silico Brain Tumor Research Center

Eventually, this kind of information could help a patient with a brain tumor get good responses to those “How long?” and “How am I going to get through this?” questions.

Joel Saltz, who leads Emory’s Center for Comprehensive Informatics, has been a central figure in developing tools for centers such as Emory’s In Silico Brain Tumor Research Center. In September 2009, Emory was selected to host one of five “In Silico Research Centers of Excellence” by the National Cancer Institute.

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Cultivating compassion while lowering stress

Charles Raison, MD

Charles Raison, MD

Charles Raison, MD, and his colleagues are studying how stress and the immune system interact to make people depressed when they’re sick and sick when they’re depressed. Yet, data show that people who practice compassion meditation may reduce their inflammatory and behavioral responses to stress, which are linked to serious illnesses. Raison is clinical director of the Emory Mind-Body Program. He also is the mental health expert on CNN’s health website, CNN Health.com.

One type of meditation, called focused meditation, aims to refine and enhance attention and calm the mind by focusing on one object such as the breath. Compassion meditation, as its name suggests, is designed to cultivate compassion—that is, enhancing one’s ability to empathize with the anguish, distress, and suffering of others.

We’re interested in how the stress system and the immune system interact to make people depressed when they’re sick and sick when they’re depressed, says Raison. There’s a circle where stress activates inflammation and inflammation activates stress pathways, Raison explains.

Secular, compassion meditation is based on a thousand-year-old Tibetan Buddhist mind-training practice called “lojong.” Lojong uses a cognitive, analytic approach to challenge a person’s unexamined thoughts and emotions towards other people, with the long-term goal of developing altruistic emotions and behavior towards all people.

To hear Raison’s own words about compassion meditation, go to “Sound Science.”

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