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Scientists at OMRF have identified a set of genes that predispose people of Korean ancestry to lupus. The findings resulted from a large-scale study of Koreans conducted by OMRF researchers Christopher Lessard, Ph.D., and Kathy Sivils, Ph.D. The two led a coalition of researchers in a global effort, which looked at genetic samples from nearly 8,000 Koreans. The findings appeared in the scientific journal Arthritis and Rheumatology. Lupus is a chronic autoimmune disorder where the body’s immune system fails to distinguish healthy cells from foreign cells, such as viruses or bacteria, and begins attacking the body’s own tissues and organs. The disease is two to three times more likely to occur in Asians, African-Americans, Native Americans and Hispanics than it is in Caucasians, according to the Lupus Foundation of America. To better understand the disease, researchers must identify genes that predispose a person to lupus. This particular project was spearheaded by the International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN), a coalition formed in 2004 to pool resources and knowledge from lupus experts around the globe in a concerted effort to make progress. “Genetic studies like this take a global effort because we need to study thousands of patients,” said Sivils. “No one center can do that alone.” The project was designed to perform a genome-wide association study in Koreans to see if scientists could find unique effects in their genetic makeup. “There is evidence to suggest that there are race-specific risk factors that we want to identify,” said Lessard. “As our sample sizes go up, our ability to find genes associated with disease improve.” Through this research, scientists were able to discover a novel set of genes important in altering genes involved in the immune system in Korean lupus patients. “The current therapies for lupus are not very specific. The goal is to define all the heritable factors that would predispose someone to getting the disease, and that is the overall mission of these SLEGEN studies,” said Lessard. “Think about it in terms of collateral damage. By discovering the exact genes involved and understanding potential race-specific triggers, we can eventually get to the point where we are tailoring therapeutic strategies around the exact reasons why you have lupus instead of blindly trying drugs without consideration of the underlying risk factors. It’s the difference between a precision-guided missile and carpet bombing.” This study is particularly important for those of Asian ancestry, because the genetics of lupus in those populations is not well defined, said Sivils. “These findings provide important new information about lupus. Many of the genes we found in Koreans are the same as in other populations. That is good because if a treatment is developed that works for those genes based on studies in other populations, we know it will be important in Asians, as well.” OMRF scientists Patrick Gaffney, M.D., John Ice, M.D., Jennifer Kelly, M.S., and Astrid Rasmussen, M.D., Ph.D., also contributed to the research. Funding for this project was provided by grant No. P01 AI083194 from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. |
Love and other drugs
As it turns out, all those pop music lyrics and Hollywood one-liners were right on target: in the human brain, love really does function a lot like a drug.
So when you’re stocking up on roses, cards and chocolate for your significant other this Valentine’s Day, you’re not just being romantic, said Oklahoma Medical Research Foundation President Stephen Prescott, M.D. You’re also feeding an addiction.
“When people experience the sensation of falling in love, it’s directed by the pleasure centers in the brain,” said Prescott. “It creates a powerfully good feeling, like everything is right with the world.”
Love itself may be too abstract or intangible for scientists to study thoroughly, but what it looks like is right in their wheelhouse. Neuroscientists have studied people who say they’re in love to see how their brains react to certain stimuli. They have learned that the brain of someone who has fallen in love looks similar to the brain of an addict.
Using scans called functional magnetic resonance imaging, or MRI, researchers at Stanford University observed that feelings of love triggered the same cells that make and receive dopamine, a chemical that stimulates the brain’s pleasure center. Dopamine can bring on a sense of euphoria and is the same chemical in the brain activated in people with addictions to drugs, gambling or overeating.
Rheal Towner, Ph.D., director of OMRF’s Advanced Magnetic Resonance Center, uses MRI to diagnose and predict the outcomes of diseases like brain cancer. While he’s no expert on love, he has spent years observing processes in the brain and said he was fascinated by the results of love studies done at Stanford.
“Functional MRI works by looking at the oxygen you use in your brain,” he said. “When you use oxygen during some sort of biological process, like thinking or moving, the corresponding area of the brain lights up on the monitor.”
To study specific responses, researchers use different stimuli like visual or auditory cues to elicit a reaction in the brain. In the case of the love study, researchers used cues like showing subjects a picture of loved one along with another photo of a stranger as a control to gauge how the reactions in the brain differed.
“You can use functional MRI to do all sorts of things. You can watch what happens when people talk about a specific topic, try to solve a difficult math problem and so on,” said Towner. “When they showed people pictures of their romantic partners or loved ones, the response in the brain was much like that of someone hooked on cocaine.”
Just as addiction to drugs or shopping can impair judgment, so can feelings of love. It might even account for all the couples that decide to elope on Valentine’s Day.
True addiction is a serious condition, said Prescott. “But if you’re going to be addicted to anything,” he said, “love is a great choice.”
Zika virus: What Oklahomans need to know
The Zika virus is spreading rapidly across the Americas, prompting the World Health Organization to declare a global emergency on Monday.
So what do you need to know about the Zika virus?
A mosquito-transmitted infection, the virus causes no symptoms and leads to no lasting harm in most who contract it. But for pregnant women, infection has been linked to a birth defect called microcephaly, which causes babies to be born with abnormally small heads and brains. More than 4,000 cases of the condition have been confirmed in Brazil since October.
“The great scare comes from all the data with respect to these birth defects, which are very dramatic,” said Oklahoma Medical Research Foundation President Stephen Prescott, M.D., a physician and medical researcher. “Affected children are born with small brains and very significant deficits in life. Experts also have linked Zika to miscarriages and other pregnancy complications, so it certainly deserves the world’s attention.”
“We do not know yet how significant the threat to Oklahoma might be, but the virus is now widespread throughout much of South and Central America,” said OMRF immunologist Hal Scofield, M.D. “There have been confirmed cases in the U.S. in persons traveling to these areas.”
Researchers predict that Southern states along the Gulf coast, in particular, could be affected because of the presence of the Aedes aegypti mosquito, an aggressive mosquito that has spread most cases of Zika. The Asian tiger mosquito, which commonly lives through the winter in Oklahoma, may also be a vector for transmission, said Scofield. However, U.S. health officials have said that the risk of a U.S. outbreak is low, largely due to more effective mosquito control.
“For the average American who is not traveling to this area, there is nothing they need to worry about,” Dr. Anne Schuchat, principal deputy director of the federal Centers for Disease Control and Prevention, told The New York Times.
There is some evidence that Zika may also be transmitted sexually, but the risk remains unknown at the time.
While it can be potentially devastating for pregnant women and their babies, the effects on others, if any, are far less severe. The most common symptoms include conjunctivitis, joint pain, fever and rash. The symptoms are often mild and last up to a week, and the need for hospitalization is uncommon. The Centers for Disease Control and Prevention say only about one in five of those infected will get sick, and most others will not even realize they have contracted the virus.
Disease specialists in Brazil say that the virus may also be causing a surge in another rare condition, Guillain-Barré syndrome, which leaves some patients unable to move and dependent on life support. Although the CDC has described reports linking the two conditions as “anecdotal,” the agency is helping Brazil conduct a study to evaluate if any connection exists.
So what’s the best way to protect yourself against Zika?
“Avoid travel to South and Central America,” said Prescott. “And don’t get bitten by mosquitoes.”
That means preventing standing water from collecting around your home and using insecticides where appropriate to prevent mosquitoes from breeding. Apply repellant when you’re going to be outdoors in peak mosquito hours. Close windows and keep sleeping areas mosquito-free, especially as temperatures start to warm.
“I know it sounds difficult to avoid getting bitten, but scale what you do to the risk,” said Prescott. “Do anything that protects you, and women early in pregnancy or planning on becoming pregnant should, as always, take the most precautions.”
UPDATE: The CDC has confirmed a sexually-transmitted case of Zika virus in Texas.
Researchers discover 10 new lupus genes in Asian population study
An international coalition of researchers led by OMRF scientist Swapan Nath, Ph.D., has identified 10 new genes associated with the autoimmune disease lupus. The findings were published in the Jan. 25 issue of Nature Genetics.
Nath and his colleagues analyzed more than 17,000 human DNA samples collected from blood gathered from volunteers in four countries: South Korea, China, Malaysia and Japan. Of those samples, nearly 4,500 had confirmed cases of lupus, while the rest served as healthy controls for the research.
From that analysis, the researchers identified 10 distinct DNA sequence variants linked to lupus, a debilitating chronic autoimmune disease where the body’s immune system becomes unbalanced and attacks its own tissues. It can result in damage to many different body systems, including the joints, skin, kidneys, heart and lungs. More than 16,000 people are diagnosed with lupus in the U.S. each year, and it affects as many as 1.5 million Americans and 5 million people worldwide, according to the Lupus Foundation of America.
“We know lupus has a strong genetic basis, but in order to better treat the disease we have to identify those genes,” said Nath, a member of OMRF’s Arthritis and Clinical Immunology Research Program. “Large-scale studies of this magnitude are becoming the gold standard for locating genes associated with autoimmune diseases like lupus.”
Thirty-seven researchers from 23 institutes, hospitals and universities in the United States, Malaysia, Korea, China and Japan took part in Nath’s study.
“These findings mark a significant advance in our knowledge base for lupus genes,” said Judith James, M.D., Ph.D., director of OMRF’s Autoimmune Disease Institute and Arthritis and Clinical Immunology Research Program chair. “For every gene we identify, it brings us closer to uncovering the trigger for this puzzling disease. It’s good news for researchers and patients alike.”
In the study, one gene in particular, known as GTF2I, showed a high likelihood of being involved in the development of lupus. “GTF2I seems to be one of the key players in lupus susceptibility,” said Nath. “Its genetic effect appears to be higher than previously known lupus genes discovered from Asians, and we surmise that it now may be the predominant gene involved in lupus.”
With these new genes identified, Nath and his colleagues can try to pinpoint where defects occur and whether those mutations contribute to the onset of lupus pathogenesis. Nath said that understanding where and how the defects arise will allow scientists to develop more effective therapies specifically targeting those genes.
The ultimate goal, said Nath, is to understand the disease better and develop personalized intervention therapies for patients based on their genetic makeup. “We are a long way from that point, but huge collaborative efforts like this help to get things going.”
OMRF scientists Celi Sun, Julio Molineros, Ph.D., Xana Kim-Howard, Prasenjeet Motghare, Krishna Bhattarai, Adam Adler and Jonathan Wren, Ph.D., also contributed to the discovery.
Funding for the project was provided by grants R01AR060366 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, R01MD007909 from the National Institute on Minority Health and Health Disparities and R21AI103399 from the National Institute of Allergy and Infectious Diseases, all part of the National Institutes of Health.
When it hurts: Choosing the right pain reliever
Choosing a pain reliever can almost be enough to give you a headache. But making the best choice doesn’t have to be complicated.
According to Oklahoma Medical Research Foundation physician-researcher Eliza Chakravarty, M.D., not all over-the-counter pain relievers are interchangeable. “It starts with knowing what each one works best for,” she said.
The three most popular over-the-counter types of painkillers are: acetaminophen (Tylenol), naproxen (Aleve) and ibuprofen (Advil, Motrin). Aspirin was once the most common pain reliever, but it has been largely supplanted by naproxen and ibuprofen, which target similar issues with fewer side effects.
If you have a headache, fever or minor pain, Chakravarty says that acetaminophen is likely the place to start. “It’s purely a pain reliever and fever reducer,” she said.
“It’s also good for people with stomach problems, kidney disease or other chronic health problems, because it has a lower risk of side effects,” she said. “But it doesn’t help relieve inflammation, and that’s its major drawback.” High doses or long-term use of acetaminophen also can cause liver damage, so that can be an issue for those who have liver problems or drink alcohol regularly.
Ibuprofen and naproxen fall into a broad category called nonsteroidal anti-inflammatory drugs or NSAIDs, a category that also includes aspirin. These drugs are also effective fever reducers and pain relievers and, unlike acetaminophen, can also relieve inflammation. Aspirin is still taken in low doses to reduce the risks of heart attack and stroke or act as a blood thinner. Chakravarty said, in general, she does not recommend taking higher doses of aspirin for pain, siding with ibuprofen and naproxen instead.
NSAIDs work by inhibiting the production of chemicals released in the body by injured cells, which trigger pain and inflammation. They are more common for short-term usage in dealing with menstrual cramps, dental pain, muscle aches, arthritis and minor injuries. While acetaminophen can be taken alone, all NSAIDs need to be taken with food.
“NSAIDs actually have more helpful properties than acetaminophen alone,” said OMRF’s Chakravarty. “The problem with NSAIDs is they can make existing kidney problems worse, and they can cause stomach ulcers, even in doses you take over the counter. So if you need to take aspirin, ibuprofen or naproxen for more than three or four days, talk to a doctor to make sure that you don’t need another medicine to protect yourself from complications or side effects.”
While all of these pain-control medications are largely regarded as safe, as with any drug, they can be dangerous if misused or overused. That’s why Chakravarty urges everyone to take time to learn the pluses and minuses of these drugs—and any drugs you take. Some products may contain more than one pain reliever, so she recommends checking ingredients before taking a new pain reliever.
“The best thing you can do is educate yourself about these products,” said Chakravarty. “If you have questions about which is best for you or need to use them for more than a few days, always check with your physician.”
OMRF accepting Teen Leaders in Philanthropy applications
The Oklahoma Medical Research Foundation is seeking applications for its fourth annual Teen Leaders in Philanthropy class.
High school students entering their sophomore, junior or senior years in the fall of 2016 are eligible to apply. The application deadline for this unique opportunity is March 1.
Students selected will have the opportunity to meet leaders from charitable foundations, nonprofit organizations, corporate donors and volunteers, as well as OMRF scientists. Through group interaction, students will learn first-hand about the fundamentals of development, board structure, networking, fundraising and effective social media usage. They will also learn how to implement these skills in their communities.
“OMRF’s Teen Leaders in Philanthropy continues to attract Oklahoma’s most energetic and compassionate high school students. We are excited to see how this generation is interested in giving back, whether it’s being a volunteer, a donor, or a non-profit professional,” said program coordinator and OMRF Director of Development Kelley McGuire.
Those selected will work together with students from a variety of schools throughout the state on a group fundraising project.
Through this experience, students will gain a deeper understanding of the nonprofit sector, develop hands-on leadership skills and will learn how to implement those skills in their community.
Participants are chosen through an application and interview process. Group sessions will start in September and run throughout the 2016-17 school year.
“We’re looking for students who don’t want to just sit back and let other people take action,” said McGuire. “It’s great watching them take their philanthropic efforts to different levels. We look forward to working with another great group of students this year.”
For additional information and applications, visit www.omrf.org/teen-leaders.
New grant funds research into a debilitating autoimmune disease
The National Institute of Dental and Craniofacial Research has awarded Oklahoma Medical Research Foundation scientist Umesh S. Deshmukh, Ph.D., a five-year, $2.14 million grant to investigate the biological origins and development of Sjögren’s syndrome.
Sjögren’s syndrome is a chronic autoimmune disorder where the body’s immune system attacks its own tissues. In Sjögren’s, the moisture-secreting glands of the eyes and mouth are adversely affected, resulting in dry mouth and dry eyes. Other symptoms include severe fatigue and joint pain.
“While there is currently no known cause for Sjögren’s, certain genes are shown to put individuals at an elevated risk,” said Deshmukh. “However, a triggering mechanism must be present, and I am looking at ways infectious biological agents might trigger the disease.”
As many as 4 million people in the U.S. suffer from Sjögren’s syndrome, and approximately nine out of every 10 patients are women, according to the Sjögren’s Syndrome Foundation. This painful disease often goes undiagnosed for several years, making basic research like Deshmukh’s critical in understanding it and developing better diagnostics and treatments for it.
OMRF scientists will conduct experiments on both mouse models and a large collection of patient samples from the Oklahoma Sjögren’s Syndrome Center of Research Translation (OSSCORT).
“This is truly a unique study, because it integrates mouse research with human clinical research,” said Deshmukh. “This is one reason for the excitement around the project, and it is only possible because of the resources available at OMRF.”
OMRF Vice President of Research Paul Kincade, Ph.D., added, “Dr. Deshmukh is a rising star, and the extremely high ranking he received on this grant is proof of that fact. It’s clear that the research he’s conducting will provide necessary understanding to make progress with Sjögren’s and other debilitating conditions.”
Deshmukh and his wife and colleague Harini Bagavant, Ph.D., were recruited to OMRF from the University of Virginia in 2013. In the lab, they work together to study environmental and biological triggers for Sjögren’s and other autoimmune diseases like lupus. Deshmukh also is interested in the role of microbes in the mouth and gut that could initiate and perpetuate those diseases.
“By investigating basic mechanisms for how Sjögren’s is triggered, we hope the discoveries will lead to therapies toward preventing dryness,” said Deshmukh. “It could also be used to develop new biomarkers, the substances that indicate the presence of disease, in humans.”
Deadline nearing for OMRF summer internship applications
The application period for the Oklahoma Medical Research Foundation’s 2016 Sir Alexander Fleming Scholar Program closes Feb. 1.
High school seniors, as well as college freshmen, sophomores and juniors, are eligible to apply. Applicants must be Oklahoma residents at the time of high school graduation and at least 16 years of age to qualify. Students selected as Fleming Scholars are paid and, if eligible, also receive free housing.
This eight-week experience features lab training under the guidance of internationally recognized scientists and physicians and top-level lectures to broaden scholars’ horizons. Students will also have opportunities to use sophisticated equipment and the latest technologies available and will complete research projects on topics such as cancer, heart disease and autoimmune diseases.
“This unique program provides an in-depth look at research and has launched many successful careers in science and medicine,” said OMRF President Stephen Prescott, M.D. “It’s an experience that can prove to be a game-changer for students at this stage in their educational journey.”
Since the program was started in 1956, more than 500 Oklahoma students have spent a summer at OMRF as Fleming Scholars. The program is named after the Nobel prize-winning scientist who discovered penicillin and dedicated OMRF’s first building in 1949.
For additional information or to apply, visit www.omrf.org/fleming.
Can you get the flu from a flu shot? Simply, no
The flu virus can spread like wildfire. It kills roughly 36,000 Americans annually and makes many more miserable.
Even with the potential danger posed by the virus, why do as many as 60 percent of Americans forgo the annual flu shot?
A big factor is the long-held belief that the flu shot itself can give you the flu. But according to scientists at the Oklahoma Medical Research Foundation, this simply is false.
“The flu vaccine that we use now does not have live flu virus in it,” said OMRF President Stephen Prescott, M.D. “The vaccine cannot infect you.”
The vaccine is made from proteins in a lab, not from the virus itself. However, your body’s immune system sees these proteins as foreign and makes antibodies that bind to them to prevent the influenza virus from infecting cells and spreading. This process prepares the body for a rapid immune response to the actual flu virus, often preventing the illness.
But a flu shot can cause mild side effects, and this is where some of the misunderstandings start.
OMRF immunologist Eliza Chakravarty, M.D., said the most common side effects are soreness, redness or swelling around the site of the injection, and some people may occasionally experience a low-grade fever. But, according to Chakravarty, this is no cause for alarm, “It’s just your body doing its job and developing protective immunity.”
These symptoms, though, won’t be anything like the full-blown flu, said Prescott, a physician and medical researcher. “The flu will give you a high fever and muscle aches all over your body. Those symptoms are usually severe, and the disease can be life-threatening.”
Very rarely, a person might get the flu after receiving the flu vaccine, but Chakravarty says not to blame it on the shot.
“In these instances, a person was already exposed to the virus,” she said. “Most likely, they were in an incubation period without symptoms, but the vaccine didn’t cause the illness. This is just coincidental and unrelated to receiving the shot. Essentially, it would just be bad luck.”
If you haven’t gotten vaccinated this year, Chakravarty urges you to do so.
“It’s never too late to get the flu shot,” she said. “We’ve found that the flu can linger within a community longer than we expected, so it’s always a good idea to protect yourself and your loved ones.”
OMRF researchers show how diabetes affects the heart
New research from the Oklahoma Medical Research Foundation has revealed how diabetes impacts a critical cellular switch in the heart.
These findings, the researchers say, can provide a better understanding of how diabetes affects the heart so that new treatments can be developed to combat the disease.
OMRF’s Kenneth Humphries, Ph.D., and graduate student Lee Bockus worked with biologically engineered mice. Their research focused on a cellular switch called PKA that controls how the heart contracts or pumps blood through the body. In particular, they sought to gain a better understanding of the disease’s specific impact on PKA.
“The heart is literally a pump that works at different workloads depending on what you’re doing,” said Humphries. “If you’re exercising or frightened, your heart beats faster. It’s often called the fight-or-flight response.”
When that response kicks in, your heart speeds up and works harder. PKA is the central switch in the heart that controls this reaction.
Humphries and Bockus discovered that PKA did not work properly in hearts of the diabetic mice. In an effort to compensate for the effects of diabetes, this switch became chronically activated, placing an unnecessary strain on the organ.
“Just like a mechanical pump, when the pump works harder it’s going to use more energy. In the body’s case it would be nutrients as opposed to gasoline or electricity,” said Humphries.
The PKA switch not only strengthens contraction of the heart muscle, it also coordinates its use of energy so that it has enough to meet these increased demands. As a result of this chronic workload, eventually the heart can stop responding.
“This fight-or-flight response is only supposed to happen in acute circumstances, like when you exercise. It’s not meant to be turned on all the time,” said Bockus. “But it happens because PKA is trying to compensate for all the problems in the diabetic heart. Over time, it can lead to clinical problems like heart failure.”
In diabetes, the body has trouble producing or responding to insulin, a hormone that tells cells to take in sugar as a source of energy. Long-term effects of the illness, which affects an estimated 300,000 Oklahomans, include heart disease and other cardiovascular conditions.
“These findings give us a better understanding of how diabetes impacts the heart,” said Humphries. “Using this new information, we can look at developing treatments to control this switch in diabetics.”
The new research appears in The Journal of Biological Chemistry. It was supported by the following grants: P20GM104934 from the National Institute of General Medical Sciences; HR13-183 from the Oklahoma Center for the Advancement of Science and Technology; and 14GRNT20510031 from the American Heart Association.
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