Peeling away pancreatic cancers' defenses

A combination immunotherapy approach that gets through pancreatic cancers’ extra Read more

Immune cell activation in severe COVID-19 resembles lupus

In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of B cells, resembling acute flares in systemic lupus erythematosus (SLE), an autoimmune disease. The findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. It also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes. The results were published online on Oct. Read more

Muscle cell boundaries: some assembly required

The worm C elegans gives insight into muscle cell assembly + architecture Read more

Medical imaging experts on quality and safety

Recently, a great deal of media coverage has focused on radiological services such as CT scans, and questions have been raised over the safety related to the increasing use of those services and the amount of radiation they deliver.

Medical imaging procedures, such as CT or CAT scans, are considered by experts to be highly useful for the diagnosis, treatment and monitoring of many medical conditions including cancer, heart disease, trauma, and liver and kidney disease. The recent increase in attention and exposure via the media is valuable, say Emory experts, in highlighting rapidly improving imaging technologies and the importance of ensuring such scans are performed in a setting where there is carefully monitoring to minimize associated radiation exposure.

CT scanner

CT scanner

Emory’s Department of Radiology is well-recognized for its expertise in all subspecialty areas of radiology and medical imaging, as well as its breadth and depth of medical physicists, researchers and educators.

Carolyn Meltzer, MD, William P. Timmie Professor and chair of the Department of Radiology in Emory’s School of Medicine, says, “Emory radiologists are the physician experts in imaging, most receiving more than 13 years of extensive training. In fact, radiologists receive substantive training in radiation biology and safety that is linked to their board certification.”

According to Kimberly Applegate, MD, vice chair of Quality and Safety for Emory’s Department of Radiology, commented on safety recently in the New England Journal of Medicine. She wrote in the article, “The medical community should continue to work together across disciplines to use existing knowledge about radiation protection to ensure that imaging is warranted and optimized.”

When patients do need imaging, they should ask if the imaging personnel are credentialed and the protocols used are weight-based and indication-based, to ensure quality, notes Applegate. Emory subspecialty radiologists work in multidisciplinary clinical teams to make sure that imaging is used appropriately, she adds.

In order to minimize radiation exposure, Emory Radiology adheres to the following guidelines: CT protocols are optimized by subspecialty-trained radiologists to ensure quality and safe imaging procedures. Further, explains Applegate, low radiation exam protocols are used when appropriate and CTs or X-rays are not performed on pregnant patients unless it is a medical emergency.

Further, in accordance with ACR (American College of Radiology) guidelines, Emory Radiology does not offer whole body screening CT exams. These tests result in unnecessary radiation and often lead to additional unneeded tests, says Applegate.

Click here for more information about radiation safety and what Emory is doing to educate all stakeholders in medical imaging and to ensure safe, high quality imaging. To learn more about medical imaging and expected radiation levels visit RadiologyInfo.

For a summary of the National Council on Radiation Protection and Measurements (NCRP) report on American radiation exposure from all sources, including medical imaging, visit The NCRP report 160: Ionizing Radiation Exposure of the Population of the United States (2009).

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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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Providing complex care for individuals in need

Emory Healthcare physicians provided $48.9 million in charity care in fiscal year 2008–2009, a total that does not include uncompensated care provided by Emory physicians practicing at publicly funded Grady Memorial Hospital and other affiliate institutions.

Charity care includes two types of care. Indigent care refers to care provided to patients with no health insurance, not even Medicare or Medicaid. Catastrophic care refers to care provided to patients who have some coverage but whose medical bills are so large that paying them would be permanently life-shattering. People without ability to pay for care are not faceless statistics to Emory clinicians but patients in need of care.

In fact, Emory’s Wesley Woods Center exemplifies Emory Healthcare’s commitment to serving patients and their families who are facing issues related to aging. The majority of the 30,000 patients treated last year at Wesley Woods’ 100-bed hospital and outpatient clinic were elderly, in their 70s, 80s, 90s and older.

But Wesley Woods also is a life-saver for many younger patients who require chronic care and specialty services for which the center is known, including wound care, rehabilitation and respiratory care, such as weaning from ventilator therapy.

Patient receives care at Wesley Woods

Patient receives care at Wesley Woods

For example, patient Sherry Smith’s CT scan at Emory University Hospital showed large blood clots blocking the vessels leading to her spleen and kidneys. Over the next two weeks, she had four operations. Surgeons removed the clots and her spleen and cut out portions of her bowel that had been destroyed by lack of oxygenated blood. She required a feeding tube and a tracheotomy to help with breathing as she recovered.

Patients can move seamlessly between the two Emory Healthcare facilities for needed care. Smith moved back and forth between Emory and Wesley Woods as she improved. She also got some unexpected help in paying for her care. When she got sick, Smith lost her job. During the six months she spent moving between the two hospitals, her bill at Wesley Woods was more than $120,000, and that at Emory University Hospital, almost $130,000.

Community Benefits Report

Community Benefits Report

 

To her relief, Emory offered to pay her COBRA insurance fees to help her maintain her insurance for the time allowed. Payments would cover only part of the actual cost of care. Wesley Woods social workers also helped Smith apply for Medicaid to cover health care costs while she continues her recovery in a rehab facility closer to her home.

Read more about charity care at Emory in the Community Benefits Report 2009.

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How muscles get stronger — and the nose knows

Scientists at Emory studying muscle repair have discovered an unexpected function for odorant receptors.

Odorant receptors’ best known functions take place inside the nose. By sending signals when they encounter substances wafting through the air, odorant receptors let us know what we’re smelling. Working with pharmacologist Grace Pavlath, graduate student Christine Griffin found that the gene for one particular odorant receptor is turned on in muscle cells during muscle repair.

The activation of the odorant receptor gene MOR23 is visible in muscle tissue in pink. Cell nuclei appear as blue.

The activation of the odorant receptor gene MOR23 is visible in muscle tissue in pink. Cell nuclei appear as blue.

Grace Pavlath, PhD

Grace Pavlath, PhD

Christine Griffin

Christine Griffin

“Normally MOR23 is not turned on when the tissue is at rest, so we wouldn’t have picked it up without looking specifically at muscle injury,” Pavlath says. “There is no way we would have guessed this.”

The finding could lead to new ways to treat muscular dystrophies and muscle wasting diseases, and also suggests that odorant receptors may have additional unexpected functions in other tissues.

While we’re on the topic of odorant receptors, a great article in November’s Howard Hughes Medical Institute Bulletin describes Emory psychiatrist Kerry Ressler’s work with Linda Buck when he was a graduate student.

From the article:

“I had never thought about smell a day in my life until I heard Linda give her talk,” Ressler says, still jazzed by the memory, “and I was absolutely blown away.” Buck had methodically identified about 1,000 odorant receptor (OR) genes and she outlined an orderly plan for decoding their function.

…Over the next three years, Ressler’s dissertation work contributed to the accomplishments that earned Buck the 2004 Nobel Prize in Physiology or Medicine, which she shared with HHMI investigator Richard Axel. Prominently displayed in Ressler’s Emory office is a framed picture of him with Buck at the Stockholm ceremony, both grinning broadly in formalwear.”

Ressler and his colleagues at Yerkes National Primate Research Center now study how fearsome memories become lodged in our brains. Since smell is often described as accessing the most primitive parts of the brain, the connection between Ressler’s past and present makes sense.

Kerry Ressler, MD, PhD, when he's not in Stockholm

Kerry Ressler, MD, PhD, when he's not in Stockholm — Parker Smith / PR Newswire, © HHMI

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Research match eases clinical trials participation

Research Match LogoIf you’d like to consider joining a clinical trial, a new secure website will make it easier. ResearchMatch.org will match any interested person living in the U.S. with researchers who are approved to recruit potential study volunteers.

Emory is one of 51 institutions participating in this first national, secure, volunteer recruitment registry. After registering at the website, potential volunteers can check out available trials. If a person indicates interest in a study, they are notified electronically about a possible match. Then they can decide whether to provide their contact information to a researcher.

The new website is sponsored by the National Center for Research Resources (NCRR) of the National Institutes of Health (NIH). ResearchMatch is the product of the NCRR’s Clinical and Translational Science Awards (CTSA) Consortium. The CTSA is a national network of 46 medical research institutions working together to improve the way biomedical research is conducted across the country.

Emory leads the Atlanta Clinical and Translational Science Institute (ACTSI), a CTSA partnership including Morehouse School of Medicine, the Georgia Institute of Technology and Children’s Healthcare of Atlanta.

ResearchMatch.org is a wonderful opportunity for those interested in participating in clinical research, says Arlene Chapman, MD, Emory professor of medicine and director of the ACTSI Clinical Interaction Network Program. It’s available to young and old, healthy or ill. And people with a rare disease can find out more about available research studies throughout the country.

The registry strictly protects anonymity. It also increases the chance to participate in local studies and saves much of the time typically spent finding out about eligibility for a particular study.

ResearchMatch is available at: www.researchmatch.org/route=emory

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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.”

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Mapping mRNAs in the brain

If the brain acts like a computer, which of the brain’s physical features store the information? Flashes of electricity may keep memories and sensations alive for the moment, but what plays the role that hard drives and CDs do for computers?

A simple answer could be: genes turning on and off, and eventually, neurons growing and changing their shapes. But it gets more complicated pretty quickly. Genes can be regulated at several levels:

  • at the level of transcription — whether messenger RNA gets made from a stretch of DNA in the cell’s nucleus
  • at the level of translation — whether the messenger RNA is allowed to make a protein
  • at the level of RNA localization — where the mRNAs travel within the cell

Each neuron has only two copies of a given gene but will have many dendrites that can have more or less RNA in them. That means the last two modes of regulation offer neurons much more capacity for storing information.

Gary Bassell, a cell biologist at Emory, and his colleagues have been exploring how RNA regulation works in neurons. They have developed special tools for mapping RNA, and especially, microRNA — a form of RNA that regulates other RNAs.

In the dendrites of neurons, FMRP seems to control where RNAs end up

In the dendrites of neurons, FMRP seems to control where RNAs end up

Fragile X mental retardation protein (FMRP), linked to the most common inherited form of mental retardation, appears to orchestrate RNA traffic in neurons. Bassell and pharmacologist Yue Feng recently received a grant from the National Institute of Child Health and Development to study FMRP’s regulation of RNA in greater detail. The grant was one of several at Emory funded through the American Recovery and Reinvestment Act’s support for the NIH.

In the video interview above, Bassell explains his work on microRNAs in neurons. Below is a microscope image, provided by Bassell, showing the pattern of FMRP’s localization in neurons.

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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.

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