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

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

Research

An invitation to be healthy and stay healthy

Predictive Health blog photoThere’s a place in Midtown Atlanta called the Center for Health Discovery and Well Being, where people can go to be healthy and stay healthy.

This fresh approach to wellness marks a new model of healthcare called predictive health, which focuses on defining and maintaining health rather than treating disease.

The Center for Health Discovery and Well Being collects and analyzes physical, medical and lifestyle histories, and up to 50 different blood and plasma tests to create a personalized health action plan for each participant. Participants also act as research partners, as data from their assessments is used to discover and develop predictive markers of health and well being. Those markers are ultimately used to create health-related interventions. What’s more, the center is part of a research partnership between Emory and Georgia Tech called the Emory/Georgia Tech Predictive Health Institute.

Located on the 18th floor of the Medical Office Tower (MOT) at Emory University Hospital Midtown, the center occupies an architecturally innovative atmosphere that includes flowing spaces, soothing colors, and a big city view.

Healthy individuals, including those with well-controlled chronic conditions, may enroll in the Center.

The Center for Health Discovery and Well Being web site offers detailed information, testimonials, and an application for participation.

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Look, don’t touch – noninvasive biochemistry

Much of the time in biochemistry, when you want to know what’s happening inside a cell you have to break them open.

Fluorescent proteins are a great tool and deserved their Nobel Prize. But you have to convince your favorite cells to make the fluorescent proteins first. It’s possible to think of specialized non-invasive probes too: dyes that change color when they encounter calcium, for example.

Now imagine being able to decipher what’s going on inside cells simply by looking at them and watching the proteins and organelles shift in response to signals. That’s essentially what Yuhong Du and Haian Fu at the Emory Chemical Biology Discovery Center have been able to do.

They use an “optical biosensor” which puts cells in front of a reflective grating. Depending on how the grating reflects light, they can measure mass redistribution inside the cells.

How the optical biosensor works

How the optical biosensor works

With this technology, they could watch for responses as cancer cells responded to signals from EGFR (epidermal growth factor receptor).

Drugs such as gefitinib and erlotinib are supposed to block those growth signals in lung cancer cells, but not every cancer responds to them. These results suggest that the optical biosensor system could be used to screen for compounds that block EGFR and many other receptors, potentially speeding up the hunt for drugs against several diseases.

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Posttraumatic stress disorder fed by avoidance

Service members returning from war historically have been haunted by traumatic memories related to combat. Problems can arise when these troublesome memories are suppressed instead of being confronted.

The military trains its service members well for combat, but teaching each individual how to deal emotionally with the trauma that comes with it is a challenge that has yet to be resolved. Unfortunately, many of those brave men and women have trouble admitting or recognizing an emotional problem. They tend to believe that avoiding troublesome memories is the best solution and do not come forward for help.

Once a service member returns home from a war zone, symptoms caused by haunting memories can arise and begin to interfere with every day activities. When those symptoms last for more than four weeks, it is likely that individual has posttraumatic stress disorder (PTSD).

Emory researcher Barbara Rothbaum, PhD, professor of psychiatry and behavioral sciences, Emory School of Medicine, and director of the Trauma and Anxiety Recovery Program, has been treating military personnel with posttraumatic stress for more than a decade, helping them to learn how to deal with the troubling memories. Through exposure therapy, the service members are taught that by re-living the traumatic event, they can begin to handle those memories when they surface. Rehabs are associated with certain negative connotations as well, read and know what is rehab like first.

Rothbaum is also a pioneer in exposure therapy using virtual reality software that was developed for both Vietnam veterans and service members returning from the war in Iraq.

Military commanders recognize that symptoms of PTSD are not as obvious as a physical injury, but nonetheless just as important, and they are ready to develop programs to quickly identify and treat active duty service members and veterans who are showing symptoms of PTSD before they worsen, says Rothbaum.

PTSD is treatable and treatments vary from exposure therapy to medication to meditation techniques. Symptoms include reliving the event; avoiding situations that stir up memories of the event; discomfort expressing feelings; being constantly on the lookout for danger; irritability; drinking or drug problems and employment, social and relationship problems.

More information on PTSD is available from the U.S. Department of Veterans Affairs. A clinical trial taking place at Emory uses virtual reality therapy for military personnel from Iraq who have PTSD.

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Congrats to the telomere/ribosome Nobelists

Congratulations to Elizabeth Blackburn, Carol Greider and Jack Szostak for the 2009 Nobel Prize in medicine. The award is for their work on telomeres, the protective caps on the ends of chromosomes that shorten with every cell division and need specialized enzymes to be replenished.

Greider, Blackburn and Szostak discovered telomerase, the enzyme that copies the ends of chromosomes using a special RNA template. Telomerase is turned off in most human cells, but cancer cells often must reactivate it so that they can keep dividing like crazy.

The discovery of telomerase has led to new leads for potential anticancer drugs. This is a good example of the impact basic research can have on medicine, since the prize-winners were not thinking about anticancer drugs in the 1980s when they were doing their work.

Telomeres are specialized protective structures at the ends of chromosomes

Telomeres are specialized protective structures at the ends of chromosomes

The telomere trio’s work relates to several lines of research at Emory.

Immunologist Cornelia Weyand and her colleagues have shown that the telomeres of T cells are abnormally shortened in patients with rheumatoid arthritis. In effect, their cells’ chromosomes are prematurely aged. This result provides some hints on how to treat autoimmune diseases.

If blood-forming stem cells can’t keep their telomeres in shape, they can’t continue to regenerate the blood. Pathologist Hinh Ly’s research has made a connection between genetic defects in telomere maintenance and bone marrow failure syndrome in human patients.

Geneticists Christa Martin and David Ledbetter have been probing the relationship between mutations or recombination in the regions of the chromosome adjacent to telomeres and developmental disorders such as autism and mental retardation.

The 2009 Nobel Prize in Chemistry, awarded to Venki Ramakrishnan, Tom Steitz and Ada Yonath, has an even stronger connection to Emory. Christine Dunham, part of a growing contingent of crystallographers here, worked on ribosome structure in Ramakrishnan’s lab at the MRC.

The ribosome is a machine that decodes mRNA and produces protein step by step

The ribosome is a machine that decodes mRNA and produces protein step by step

She is examining the molecular details of how antibiotics and viruses perturb ribosome function.

What the two Nobels have in common is that they both honor work on molecular machines containing RNA, connections to the ancient, shadowy “RNA world“.

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Heart and depression: learning from twins

Just like diabetes and hypertension, depression is a prevalent medical condition that is highly treatable. However, if ignored, it appears to increase the risk for heart disease. Researchers at Emory are continuing studies related to the link between depression and heart disease as a result of a 2-year, $1.5 million grant from the National Institutes of Health (NIH) through the 2009 American Recovery and Reinvestment Act.

Lead investigator, Viola Vaccarino, MD, PhD, professor of cardiology at Emory School of Medicine, is looking at the relationship between depression and heart disease, specifically researching the potential mechanisms.

Vaccarino says although depression has been implicated as a risk factor for heart disease for many years, there is still question whether this is a causal association or whether there are other reasons why people who are depressed may be more likely to get heart disease. Clarification of these mechanisms will improve our understanding of the disease and ultimately point to more effective primary prevention strategies for the identification and treatment of high-risk individuals.

Vaccarino and her team will study twin males born between 1946 and 1956 from the Vietnam Era Twin Registry comparing one twin who has depression and one who does not. She says this is almost a natural experiment, allowing researchers to separate out genetics and influences from the environment or behavior.

Vaccarino will be looking at myocardial blood flow measured with PET, a common imaging technique of the heart. It can quantify exactly how much blood is going to the coronary arteries in the heart and carefully determine if depression is associated with decreased blood flow to the heart.

This grant builds on a previous project looking at the same population of twins and allows researchers to bring these twins back and compare two time points. Researchers measured myocardial blood flow with PET a few years ago and will now be able to monitor progression of heart disease over time

Learn more about Emory’s stimulus grant funding.

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Emory HIV/AIDS experts lends voice to reach out

The latest CDC statistics on HIV/AIDS estimate more than 1.1 million persons in the United States are living with diagnosed or undiagnosed HIV/AIDS. HIV gradually attacks the immune system and causes AIDS, the final stage of HIV infection.

It can take years for a person infected with HIV to reach this stage. Having AIDS means that the virus has weakened the immune system to the point at which the body has a difficult time fighting infection. Early HIV diagnosis is vital, so people who are infected can fully benefit from available live-saving treatments.

David Malebranche, MD

David J. Malebranche, MD

This critical message is the foundation of a new campaign titled “Treatment is Power.” David J. Malebranche, MD, MPH, assistant professor of medicine at Emory University School of Medicine and internist at Grady Memorial Hospital is an expert voice for the campaign by Gilead Sciences. Listen to Malebranche on a public service announcement (MP3).

Malebranche says opportunity is unique in reaching people living with HIV. It is geared toward reducing the stigma and fear associated with taking medications that slow down the virus and helps individuals realize the many quality of life improvements associated with early treatment.

As a nationally recognized speaker and advocate, the idea that “treatment is power” is not a new theme for Malebranche. Fostering a close working doctor-patient relationship is one Malebranche aggressively promotes at the Ponce Infectious Disease Center – a local AIDS clinic in downtown Atlanta, where he delivers comprehensive care to uninsured patients living with HIV/AIDS.

He says early treatment is an essential part of the fight against HIV.

From 2006-2008, Malebranche served on the Presidential Advisory Council on HIV/AIDS, which provides recommendations to the President and the U.S. Department of Health and Human Services regarding national and international HIV/AIDS programs and policies. He conducts research exploring the social, structural and cultural factors influencing sexual risk-taking and HIV testing practices among black men.

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Evolution doesn’t run backwards: Insights from protein structure

“The past is difficult to recover because it was built on the foundation of its own history, one irrevocably different from that of the present and its many possible futures.”

Whoa. This quote comes from a recent Nature paper. How did studying the protein that helps cells respond to the stress hormone cortisol inspire such philosophical language?

Biochemist Eric Ortlund at Emory and collaborator Joe Thornton at the University of Oregon specialize in “resurrecting”and characterizing ancient proteins. They do this by deducing how similar proteins from different organisms evolved from a common root, mutation by mutation. Sort of like a word ladder puzzle.

Ortlund and Thornton have been studying the glucocorticoid receptor, a protein that binds the hormone cortisol and turns on genes in response to stress. The glucocorticoid receptor is related to the mineralocorticoid receptor, which binds hormones such as aldosterone, a regulator of blood pressure and kidney function.

If these receptors have a common ancestor, you can model each step in the transformation that led from the ancestor to each descendant. But Ortlund says that protein evolution isn’t like a word ladder puzzle, which can be turned upside-down: “You can’t rewind the tape of life and have it take the same path.”

The reason: Mutations arise amidst a background of selective pressure, and mutations in one part of a protein set the stage for whether other ones will be viable. The researchers describe this as an “epistatic rachet”.

Mutations that occurred during the transformation between the ancestral protein (green) and its descendant (orange) would clash if put back to their original position.

Mutations that occurred during the transformation between the ancestral protein (green) and its descendant (orange) would clash if put back to their original position.

This work highlights the increasing number of structural biologists like Ortlund, Christine Dunham, Graeme Conn and Xiaodong Cheng at Emory. Structural biologists use techniques such as X-ray crystallography to figure out how the parts of biology’s machines fit together. Recently Emory has been investing in the specialized equipment necessary to conduct X-ray crystallography.

As part of his future plans, Ortlund says he wants to go even further back in evolution, to examine the paths surrounding the estrogen receptor, which is also related to the glucocorticoid receptor.

Besides giving insight into the mechanisms of evolution, Ortlund says his research could also help identify drugs that activate members of this family of receptors more selectively. This could address side effects of drugs now used to treat cancer such as tamoxifen, for example, as well as others that treat high blood pressure and inflammation.

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Obesity ups risk for endometrial cancer

Increasing numbers of obesity in both men and women nationwide are resulting in a growing rate of multiple health consequences. Recent research suggests that overweight women are at an increased risk of developing endometrial cancer, especially if menopause occurs in women younger than age 45.

One study has found that women with a body mass index (BMI) of greater than 35, who experienced their last menstrual period at an age younger than 45, had more than 20 times the risk of developing endometrial cancer than normal-weight women.

BMI is a measure of body fat based on height and weight that applies to both adult men and women. A BMI of 18.5 to 24.9 is considered normal weight, 25 to 29.9 is considered overweight and a number over 30 is considered obese.

Mary Dolan, MD, MPH, assistant professor of gynecology and obstetrics, Emory School of Medicine, notes that experts already know that obesity is linked to cardiovascular disease, high blood pressure, diabetes, joint complications and other diseases. Now the connection between obesity and endometrial cancer is on experts’ radar.

Mary Dolan, MD, MPH

Mary Dolan, MD, MPH

Endometrial cancer forms in the tissue lining the uterus or endometrium – the lining that is “shed” monthly during menstruation. Endometrial cancer is more common in older women and fortunately is usually diagnosed early since it causes abnormal bleeding, says Dolan.

In a report published recently, Dolan and colleagues from the Centers for Disease Control and Prevention (CDC) discuss findings from a review of data from the Cancer and Steroid Hormone study from the 1980s. This study examined the relationship between oral contraceptive use and breast, ovarian and endometrial cancers in women ages 20-54 years.

Since many of the study patients with endometrial cancer were overweight, the study gave researchers an opportunity to look at the risk for endometrial cancer among younger, overweight women using BMI.

The study found that women who were younger than 45 when they had their last period and had a BMI over 35 had a 21.7 times greater risk of developing endometrial cancer than a woman of normal weight.

In comparison, older women with a BMI of 35 or higher, who had their last period at age 45 or older, had a 3.7 times greater risk of developing endometrial cancer than a woman of normal weight.

Elevated risks were also seen for women who had been overweight or obese at age 18 and who had their last period before age 45.

Dolan says obesity can lead to higher levels of estrogen because of chronic “anovulation,” where a woman fails to ovulate. Because the condition brings on irregular or no menstruation, estrogen levels remain high while opposing progesterone levels remain low. Experts believe this combination leads to an increased risk of endometrial cancer.

Dolan says physicians need to counsel patients even more to maintain a healthy weight. By both losing weight and then maintaining it, a woman’s risk for endometrial cancer likely decreases.

This study is one of only a few which have focused on younger women and the relationship between obesity and endometrial cancer. The results were published in the July 2009 issue of Obstetrics & Gynecology

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Attending to neglected tropical diseases

As Georgia’s immigrant and refugee communities grow, so do Georgia’s cases of infectious tropical diseases. Also known as neglected tropical diseases, these illnesses are endemic in some low-resource countries and cause considerable disability and dysfunction.

Carlos Franco-Paredes, MD, MPH

Carlos Franco-Paredes, MD, MPH

Carlos Franco-Paredes, MD, MPH, a researcher and clinician at the Emory TravelWell Clinic at Emory’s midtown campus, provides pre- and post-travel health care to international travelers, including faculty, staff, students, business travelers and missionaries. Franco-Paredes, an expert in infectious diseases, also treats immigrants and refugees affected by neglected tropical diseases. He and colleagues recently received funding to study the epidemiology and treatment outcomes of tropical infectious diseases in immigrant and refugee communities in Georgia.

With a grant from the Healthcare Georgia Foundation, Franco-Paredes and his colleagues are assessing the prevalence and the outcomes of hepatitis B, Chagas disease and leprosy.

In fact, the clinic is the main referral center for leprosy in the region, and physicians there currently care for about 25 patients with leprosy, a chronic disease. Most of the cases are found in foreign-born individuals, particularly patients from Central and South America and Asia.

Franco-Paredes’ collaborators include Uriel Kitron, PhD, Emory professor and chair, Environmental Studies, and Sam Marie Engle, senior associate director, Emory’s Office of University Community Partnerships.

To hear Franco-Paredes’ own words about his research into neglected tropical diseases, listen to Emory’s Sound Science podcast.

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Reality check for HIV vaccine design

HIV doesn’t have a brain and it doesn’t strategize.

But the way that the virus mutates and evades the immune system in the early part of an infection, you might think it did.

Emory Vaccine Center researcher Cynthia Derdeyn and her colleagues have a new paper in PLOS Pathogens that is a reality check for researchers designing possible HIV vaccines. The results come from a collaboration with the Rwanda Zambia HIV Research Group. (Although the patients in this paper are from Zambia only.)

Red and green depict the parts of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems. The rest of the envelope protein is blue.

Red and green depict the parts of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems.

Recently there has been some excitement over the discovery of robust neutralizing antibodies in patients.

The bottom line, according to Derdeyn’s team: even if a vaccine succeeds in stimulating antibodies that can neutralize HIV, the virus is still going to mutate furiously and may escape those antibodies. To resist HIV, someone’s immune system may need to have several types of antibodies ready to go, their results suggest.

A companion paper in the same issue of PLOS Pathogens from South African scientists has similarly bracing results.

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