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Discoveries That Make a Difference

Military students receive summer science training at OMRF

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Three students from United States military academies have completed biomedical research summer internships at OMRF.

Two students from the U.S. Naval Academy in Annapolis, Md., and one from the U.S. Air Force Academy in Colorado Springs, Colo., participated in the foundation’s ninth annual John H. Saxon Service Academy Summer Research Program. 

Oklahoma City native and Heritage Hall High School graduate Paige Miles is a midshipman at the U.S. Naval Academy. She worked in the lab of Courtney Griffin, Ph.D., studying blood vessel development.  

“Both of my parents are doctors in Oklahoma City, so when I heard about this opportunity I jumped at the chance to not only get experience working in medical research but also to move home for a few weeks,” said Miles. “This has been an unbelievable opportunity, and I am so fortunate have the chance to work with a great scientist like Dr. Griffin.”

Connor King, also a midshipman at the Naval Academy, investigated cell division under the guidance of researcher Roberto Pezza, Ph.D. The Suffolk, Va., native researched a protein involved in DNA recombination and its function in cell development. 

“I have a pre-medical focus, and this experience has had a big impact on me because it shows the lifetime of research and work that goes into making each of these discoveries,” said King. “It really changes your perspective on the value of research science.”

Finally, U.S. Air Force Academy cadet Lionel Gumireddy studied the impact of diabetes on the heart with OMRF scientist Kenneth Humphries, Ph.D. Gumireddy worked on an enzyme that has been linked to diabetes.

“I’ve learned even more than I expected, and I have loved every minute of the experience,” said Gumireddy, a Pittsburgh, Pa., native. “I’m trying to be a doctor in the Air Force, and I’m leaning toward critical care transport. This introduction to the research side of medicine has been eye-opening.”

Muskogee physician John Saxon, III, M.D., established the program to honor his late father, a West Point graduate and Air Force pilot.

“This exposure to real-world medical research is invaluable to the students, and it also adds needed help and fresh perspectives in our labs,” said OMRF Senior Human Resources Specialist Heather Hebert, who coordinates the program. “We’re grateful to Dr. Saxon for supporting this unique program.”

New clues in fight against food allergies

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Peanuts. Shellfish. Eggs. Milk. While that may look like a grocery list to some, to those who are allergic to these common foods, it reads like the start of a horror novel.

More than 50 million people in the United States suffer from at least one food allergy, and many can result in serious health problems and even death. Allergic reactions to food are most common in children, with the Centers for Disease Control and Prevention reporting 4 to 6 percent of youngsters in the U.S. are affected.

With food allergies making such a significant impact on the population, are we any closer to solving the issue?

“We don’t yet have all the answers, but we’ve found some important new clues in recent years,” said OMRF President Stephen Prescott, M.D.

Food allergies occur when the body has a specific immune response to a food. While our immune system is designed to fight off foreign invaders like viruses to keep us healthy, occasionally it can incorrectly identify a harmless substance—like peanuts or shellfish—as a threat.

Prescott said for many years, health experts focused on identifying allergens and telling people to stay away from those offending foods.

“This resulted in stringent requirements for food labels and measures like peanut-free classrooms,” he said. “Still, the prevalence of peanut allergies kept increasing.”

In an effort to understand why, scientists studied hundreds of infants deemed at high risk of developing a peanut allergy. They randomly assigned some of the babies to be regularly fed peanut products, while denying the others all foods containing peanuts.

By age 5, less than 2 percent of those children fed peanuts developed an allergy, compared to almost 14 percent of those who’d avoided peanuts. A second study involving children who already showed peanut sensitivities at the beginning of the study yielded similar outcomes.

“These findings suggest that we’ve been going about things all wrong,” said Prescott, a physician and medical researcher. “Instead of protecting kids from food allergens at young ages, it looks like we’d do better by exposing them.”

Indeed, the National Institute of Allergy and Infectious Diseases has issued new guidelines recommending giving babies puréed or finger food containing peanut powder or extract before they are six months old.

“If parents follow this advice, I’d hope to see the peanut allergy numbers start to drop in the coming years,” said Prescott. “If that happened, it would be a big step forward.”

Five ways to make the most of Men’s Health Month

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From Father’s Day to the U.S. Open and World Cup, June can be a pretty good month for guys. It’s also Men’s Health month, which makes it a good time for men to focus on their wellbeing.

OMRF President Stephen Prescott, M.D., has five tips to help men live longer, healthier lives:

  1. Shape up

Having an “apple” shape increases the risk for disease and death. A 2014 study from the Annals of Internal Medicine found that a man of normal body mass index with an abnormally large belly has an 87 percent higher risk for death than a man with the same B.M.I. but a normal waist-to-hip ratio.

“Eliminating belly fat is especially deadly when it comes to heart disease in men,” said Prescott, a physician and medical researcher.

  1. Move it 

After a long day, the lure of the sofa or recliner can be overwhelming. But a sedentary lifestyle may literally be killing us.

“Research has shown that sitting for long periods of time is harmful to our health and can lead to heart disease and even death,” said Prescott. He recommends avoiding prolonged periods of inactivity. “No matter what you’re doing, make a point of getting up and walking around every hour.”

  1. What’s up, doc?

“A lot of men’s health issues can be detected or avoided through an annual physical exam,” he said. Many men put them off until it’s too late.

Getting your blood pressure checked can give you an upper hand in evading strokes and heart attacks. Annual blood work can often reveal problems before medical intervention is needed.

Colon cancer is another major killer of men, so it’s important to start colonoscopies at age 50, Prescott said. And prostate cancer is fairly common in men. “If you have risk factors or a family history, talk to your physician about getting screened, especially if you’re older.”

  1. Take a shot 

Whatever your age, vaccinations can go a long way toward preserving your health.

The annual flu shot is critical, as the flu kills up to 50,000 Americans annually. It is also crucial to make certain you’ve received your TDaP or DTaP combo vaccination for tetanus, diphtheria and pertussis (whooping cough). Once you’ve had the first one, you need a tetanus and diphtheria booster every 10 years. And the new shingles vaccine is also a must for men (and women) after age 50.

  1. Have a drink (but not 2 or 3)

In moderation, alcohol consumption seems to benefit your health. Studies show that moderate alcohol consumption—about one drink per day—correlates with reduced risks of heart disease, ischemic stroke, diabetes and certain cancers.

“Drinking too much is always bad for your health,” said Prescott. “But evidence is mounting that light drinkers have a lower overall risk of mortality even than those who don’t drink.”

More research is needed to understand why this might be true, he said. “In the meantime, a glass of wine with dinner seems to be just what the doctor ordered.”

New hope in the fight against sickle cell disease

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When Mary Long became pregnant with her first child in 1970, her feet felt as if they were being stuck with needles. Her hands throbbed. Eventually, the pain forced her to stop working. Blood tests revealed her pain stemmed from a form of sickle cell disease.

She really can’t remember a time when she wasn’t in pain, even from childhood. But the answer to her pain may, literally, be right around the corner.

Long has worked at the Oklahoma Medical Research Foundation for more than 30 years alongside researchers who’ve made new discoveries in the disease that has impacted every day of her life.

In SCD, red blood cells change from their customary round or oval shapes to the form of a crescent or “sickle.” Unlike normal cells, which are pliable and slide easily through the blood vessels, sickled cells become hard and sticky. They stack up inside vessels, which eventually results in inflammation and excruciating pain. In some cases, long-term lack of oxygen can lead to organ damage, stroke or even death.

June 19 is World Sickle Cell Awareness Day, bringing attention to a disease that affects millions globally. The disease can affect people of all races, but it’s most prevalent in those with African-American heritage, like Long. Health authorities estimate that 100,000 people in the U.S. suffer from SCD, which has no known cure.

Since the 1980s, Long has been a member of the staff that cleans the foundation’s offices and labs, ensuring that researchers at OMRF can focus their time and attention on developing a deeper understanding of human biology. One of those researchers is Rodger McEver, M.D., who started his lab at OMRF a few years after Long came aboard.

McEver trained as a hematologist, a physician who specializes in blood disorders, and focused his research on white blood cells. Specifically, he studied P-selectin, a protein that mobilizes white blood cells to hunt down and stop invaders like bacteria in the body. McEver and his colleagues created an antibody that blocks P-selectin’s functions. Research indicated that, in laboratory mice, P-selectin worsened sickle cell disease symptoms.

To explore clinical applications in humans, McEver helped create a biotechnology company, Selexys. The company fine-tuned the antibody, making an experimental drug that bound to human P-selectin and blocked its function.

An initial round of clinical testing found the drug to be safe and well tolerated by patients. Then, in a larger, multi-center trial in the U.S., Jamaica and Brazil, the medication showed a marked reduction in pain crises suffered by SCD patients.

Based on those results, the pharmaceutical company Novartis purchased Selexys and its experimental drug in late 2016. McEver hopes the medication, now known as SEG101, will soon be approved for treatment of sickle cell disease.

“As a physician, I’ve seen these patients,” McEver said. “Their suffering is extreme. SEG101 is still not the ultimate cure, but I hope it will help a lot of people until we can do more.”

Long hopes McEver’s drug will be a success and that news of it might also encourage some who’ve lived with SCD to seek assistance.

“If you don’t talk about it, you might never know who could help you,” she said. “Dr. McEver has used his knowledge, and it might make life better for many who suffer with sickle cell disease. I really hope it happens.”

Discovery could help treat Tylenol overdoses

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Acetaminophen, sold over the counter as Tylenol, is one of the world’s most widely used pain relievers. But too much of the drug can lead to serious liver damage.

Now, new research from OMRF has pinpointed the cause of liver bleeding during acetaminophen overdose. OMRF scientists have also discovered a new potential treatment for the condition, which often strikes users of Percocet and Vicodin, pain medications that also contain acetaminophen.

OMRF scientists Courtney Griffin, Ph.D., and Siqi Gao discovered that a marked increase in the activity of an enzyme called plasmin caused liver bleeding in the event of acetaminophen overdose.

“It was well known that acetaminophen, like most drugs, is metabolized in the liver. When you get too much of it, toxic byproducts start to build up and can damage liver cells,” said Gao, who is also a Ph.D. student at the University of Oklahoma Health Sciences Center. “It was also known that a lot of plasmin is generated in acetaminophen overdose, but it wasn’t clear why.”

Griffin and Gao broke new ground by making a connection between plasmin activity and liver bleeding following acetaminophen overdose. While this finding is important on its own, Griffin said, the OMRF researchers also made a related discovery that yielded important treatment options for overdose patients.

In laboratory mice, the scientists were able to reduce plasmin levels through treatment with tranexamic acid, a prescription medication used to prevent excess blood loss from major trauma or surgeries.

“If the plasmin is breaking down the blood vessels and causing them to rupture, this can help dampen that effect to prevent excessive bleeding,” said Griffin.

In humans, it’s possible that treating this bleeding with tranexamic acid could help facilitate liver recovery from an overdose and also lessen the damage, said Griffin. “We think it can certainly protect against the bleeding itself, but its role in overall liver recovery is still unknown. That’s the next step for this work.”

The treatment impact of the findings could be significant, said Griffin, especially since tranexamic acid has already been approved by the Food and Drug Administration for another condition.

“It could be administered soon after a patient arrives at the hospital,” she said. “We are excited to see where the next stage takes us.”

The new findings were published in the journal Hepatology. OMRF researchers Florea Lupu, Ph.D., and Robert Silasi-Mansat, Ph.D., also contributed to the findings. This work was supported by grant No. P30GM114731 from the National Institute of General Medical Sciences, a part of the National Institutes of Health.

OMRF announces 2018-19 Teen Leaders in Philanthropy

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The Oklahoma Medical Research Foundation has announced its sixth annual Teen Leaders in Philanthropy class.

The 2018-19 class includes 50 teenagers from 28 high schools across the Sooner State. Five members from last year’s class will return to serve in an advisory council capacity.

Selected students will visit OMRF’s Oklahoma City campus monthly throughout the 2018-19 school year to meet with philanthropic leaders, study the functions of nonprofit organizations, and learn the impact charitable giving makes on a community.

The teens will work on team-building and fundraising projects designed to instill them with the knowledge and skills required for philanthropy, development, networking, fundraising and board service.

“Every year this program continues to empower Oklahoma teens with the tools they will need to become fully engaged in their communities in meaningful ways,” said OMRF Development Associate Caroline Allen. “They gain the knowledge and teamwork skills that will give them confidence to go into their hometowns and local organizations and make an impact. This is just the first step in the journey for all of these promising youngsters.”

Past Teen Leaders classes have worked together to create, organize and operate community events to raise funds for research at OMRF.

The 2018-19 Teen Leaders in Philanthropy are:

  • Bishop McGuinness — Hannah Lee, Ryan Schwartz
  • Booker T. Washington — Mackenzie Toliver
  • Carl Albert — Taryn McLaughlin
  • Choctaw – Grace Anderson Jayke Flaggert
  • Crossings Christian — Delany Barghols
  • Classen SAS — Olivia Griffin, Delancey Griffin, Lauren Roberts
  • Dove Science Academy — Iris Amaya, Kim Cabrera, Gil Lara
  • Edmond Memorial — Rohan Rajeev
  • Edmond North — Sara Azzun, Katie McDonough
  • Edmond Santa Fe — Shreya Kumar
  • Epic Charter — Evan Smartt
  • Harding Charter Prep — Gwen Herrada
  • Heritage Hall — Sean Cudd, Ryan Thompson
  • Mount Sant Mary — Stephanie Rojas
  • Mercy School Institute — Sidra Jawaid
  • Mustang — Brittney Tran
  • Norman — Lily Arnold, Katie Kernal, Charlotte Mancino, Katherine McPherson, Elisa Velasco
  • Norman North — Caden Geist, Emma Hickman, Kayton Kite, Isabelle Pence
  • Oklahoma Bible — Coulter Freeman
  • Oklahoma Christian School — Joyce Tullis
  • Oklahoma School of Science & Mathematics —Nitya Arekatla, Carly Bixler, Kevin Thomas
  • Santa Fe South Pathways Middle College — Ricky Chavez
  • Tuttle — Alli Hodges, Lauren McDaniel
  • Western Heights — Rose Nguyen, Jen Rios, Nick Sayegh
  • Westmoore — Aaliyah Ramos

Protect yourself from the summer sun

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From stinging, blistering and swelling to more serious side effects like headache and nausea, even a run-of-the-mill sunburn can make you wish you’d applied your sunscreen before going out in the sun.

But as bad as the instant regret can be, the long-term effects pose the most substantial threat, said OMRF President Stephen Prescott, M.D.

“A number of issues can arise over time, including premature aging, deep wrinkles, eye damage and, most significantly, skin cancer,” he said. “Ultimately, the takeaway is: sunburns are bad news and can have serious consequences.”

Although most people are aware of the dangers burns can present, that doesn’t mean they’re taking the necessary precautions. In fact, the Centers for Disease Control and Prevention report that more than one-third of adults and 70 percent of children have been sunburned within the past year.

Those numbers, particularly in children, strike Prescott as alarming.

“There is a clear link between sun exposure and certain types of skin cancer. This is particularly true when children and young adults get bad burns, because it gives problems a longer time to develop as they age,” said Prescott.

“It’s almost impossible to prove, but many experts think even one bad burn, particularly in childhood, can make the mutations in your DNA that will eventually lead to cancer,” he added.

It’s not the acute burn itself that proves to be dangerous, he said. The infrared rays that cause you to look red or pink when you come out of the sun can cause pain and blistering, but it’s rare that a sunburn is severe enough to require medical attention. It’s the other rays—ultraviolet rays—in sunlight that cause longer-term issues.

Ultraviolet rays are the leading factor in causing skin cancer, the most common cancer in the U.S. In fact, more people have suffered from skin cancer than all other cancers combined over the past three decades, according to the Skin Cancer Foundation.

And sunlight might not be your only enemy when it comes to UV rays. Prescott said even tanning beds can lead to many of the same skin issues and elevated cancer risks.

Thankfully, the solution is a simple one: if you’re going to be exposed to the sun, wear sunscreen. You can also cover up with hats, long-sleeves and pants.

It’s important to note that all sunblock is not created equal, Prescott said. Use something that blocks UV rays, and the higher the SPF the better. OMRF’s Prescott recommends using SPF 30 or higher to be safe.

“We all want to have fun outdoors in the summer at barbeques and lounging by the pool, but taking a few minutes to apply proper sun protection can make a world of difference in the long run,” he said.

OMRF secures $2.6 million flu grant

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OMRF scientist Jose Alberola-Ila, M.D., Ph.D., has received a five-year grant from the National Institutes of Health to study a novel population of cells that appear to be protective against influenza.

The grant, awarded by the National Institute of Allergy and Infectious Diseases, will provide Alberola-Ila with $2.69 million to investigate the role a type of white blood cell plays in mounting the body’s response against flu infection.

In preliminary experiments, Alberola-Ila found that laboratory mice with greater numbers of these cells (known as NKT cells) were better protected from the virus.

“All the mice we looked at had the flu, but the ones with more of these cells lost less weight, got less sick and recovered faster,” said Alberola-Ila. “We don’t yet know exactly why the mice responded the way they did, and that is exactly what this new grant will allow us to find out.”

Alberola-Ila said if he and his OMRF research team are able to determine how these cells behave during an influenza infection, this could provide new leads on ways to improve flu vaccines. “A stronger and more protective response means a better vaccine, and that’s something our world needs.”

This year’s flu season proved to be one of the worst in decades, and the flu shot proved relatively ineffective against the primary strain, H3N2. Since the beginning of the flu season in September, the Oklahoma State Department of Health has reported 285 deaths and more than 4,700 hospitalizations.

Alberola-Ila, who joined OMRF’s scientific staff in 2005, said developing a universal flu vaccine is one of the highest public health priorities in the world, and anything researchers can learn about better protective methods is a step in that direction.

“The flu virus is deadly, and the fact that we need a new vaccine every single year is a huge and expensive process that can be very inefficient,” he said. “What we are learning could be a very real way of improving vaccination strategies in the long term, and that is an exciting opportunity.”

The grant, R01 AI129458-01A1, is funded through NIAID, a part of the NIH.

Debugging: How to avoid insect-borne diseases

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With temperatures on the rise, insects are once again spreading disease. And it’s happening faster than it ever has before.

The Centers for Disease Control and Prevention reports that the number of Americans infected by Lyme disease, West Nile virus and other insect-borne illnesses has more than tripled since 2004, jumping from 27,388 cases to more than 96,000 in 2016.

According OMRF President Stephen Prescott, M.D., climate change appears to be a key driver for this trend.

“In the southern U.S. and Gulf Coast, we are seeing real changes in the types of mosquitoes that can survive there,” said Prescott. “More parts of the country look increasingly like the climate in Brazil and other tropical areas, so diseases we previously only associated with those places are now here, even in Oklahoma.”

Other contributing factors include the increase in global travel, a return of forestation in urban areas and suburbs, and a lack of new vaccines to combat the new threats, said Prescott.

In Oklahoma, the most common insect-borne diseases are West Nile virus, which is spread by mosquitoes, and Rocky Mountain spotted fever, which ticks pass from animals to humans.

“There are a lot of bad diseases here in Oklahoma already, and many more could be on the way. Some of them you might not even have heard of yet, like chikungunya or dengue,” said Prescott. “These can do serious damage to your health, and we need to be prepared for their arrival.”

So, how do you protect yourself?

The best defense, Prescott said, is to keep insects off your skin. “Whether you wear long sleeves and pants, use an insect repellent with DEET, or both, you are taking a crucial step,” he said.

Using insect repellant, said Prescott, doesn’t pose a risk. “There is no evidence that regular application in this circumstance is detrimental to your health. It represents far less risk than getting bitten by an infected insect.”

He also suggests limiting outdoor activities around dusk and dawn, when insect activity is at its highest. If you’re outdoors in the early mornings or evenings, avoid walking through grass, where you’re most likely to attract mosquitoes and ticks.

To help control insect populations, Prescott recommends dumping out flower pots that contain excess water and making sure gutters or storm drains aren’t full or clogged. Routinely change water in bird baths and pet water bowls, too, he said.

“The best advice I can give is this: do whatever it takes to avoid getting bitten by mosquitoes,” said Prescott.

You never outgrow the need for vaccines

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Although you may associate them with childhood, vaccines remain important at any age.

“Vaccinations are an important part of staying healthy for all adults,” said OMRF President Stephen Prescott, M.D.

For starters, he said, make a point of getting the annual flu shot. It’s an every-year necessity, as the virus mutates constantly.

“The flu shot is one that we know we should get, but that doesn’t mean we all get it,” said Prescott. “It’s not perfect, but it is your single best defense against the flu.”

The combined vaccine for tetanus, diphtheria and pertussis (known as whooping cough) should also be on your checklist, said Prescott. All adults should receive this vaccine—known as DTaP or TDaP—if they didn’t as children, and then a tetanus and diphtheria booster every 10 years after.

Since the introduction of the vaccine, cases of tetanus and diphtheria have dropped by 99 percent, and whooping cough has been reduced by 80 percent. But those numbers are expected to climb.

“I really encourage this for protection from all three, but pertussis in particular has had a large resurgence in adults because of the waning in immunization for children,” said Prescott.

Two more key vaccines come along once you’re a little longer in the tooth.

The FDA recently lowered the vaccination age for shingles to 50, and doctors say the new shingles vaccine, Shingrix, is a must.  It’s also recommended that you get the new vaccine even if you’ve previously received the first shingles vaccine, Zostavax.

“If you have ever had chicken pox, the shingles virus is already in your body, and as you get older your immune system becomes less equipped to keep it at bay,” said Prescott. “This new vaccine is superior and everyone should get it as soon as they are eligible. The risk rises with age, so get it as soon as you can to be safe.”

Another must-have for adults age 65 and up is the pneumococcal vaccine. The CDC also recommends the vaccine for children younger than 2, but it’s important to receive it again later in life.

Pneumococcal symptoms can range from ear and sinuses infections to pneumonia and bloodstream infections. It can even be fatal. There are two primary vaccines for pneumococcus, PCV13 and PPSV23, that you should receive about one year apart.

Other vaccines are a little more specialized and the need for them depends on your lifestyle, travel habits, health condition or other factors. These include yellow fever, hepatitis A and B, and HPV. If you never received the MMR vaccine—measles, mumps and rubella—you should also consider getting one now because the number of cases is on the rise as fewer people immunize their children.

“You should ask your doctor for advice on which additional ones you need for your circumstances,” said Prescott. “The important takeaway message is: get vaccinated. Many of the vaccines you’ll need as you age will give you the best shot at long-term health and can even save your life.”

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