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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 hope in the fight against sickle cell disease
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
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 secures $2.6 million flu grant
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.
OMRF hosts 2018 Loyal Donors reception
On Thursday, May 14, officials at OMRF brought more than 110 long-time donors together from across the state for the annual Loyal Donor Society reception at the foundation in Oklahoma City.
Every person who donates to OMRF has a unique and personal reason for giving to research, said OMRF Senior Director of Development and Gift Planning Ginny Carl, who helped with the event.
For Margaret Vater, it’s about finding a cure for brain cancer, which has taken the lives of two of her family members. John and Mary Ann Coates, began giving as a way to honor John’s late father, who died from heart disease; now they have been donating to disease research for 45 years.
For Charles and Alysa Newcomb, it’s a double-whammy: taking advantage of the biomedical tax credit and supporting valuable disease research simultaneously. Leah Beale donates in memory of her mother, who was treated at the old research hospital at OMRF in the 1970s.
OMRF established the Loyal Donor Society to celebrate the foundation’s most consistent donors, recognizing those who have made donations to the nonprofit biomedical research institute for a minimum of five years.
“We couldn’t do what we do without the support of individuals like this group coming together for the betterment of all our health,” said Carl. “OMRF started as a grassroots effort, and loyal Oklahomans are still the backbone of our support system.”
As a part of the evening’s program, OMRF President Stephen Prescott, M.D., provided a brief history of the nonprofit research institute and the critical role philanthropic giving plays in establishing the foundation of support for nonprofits like OMRF.
From there, donors broke off into small groups and worked in five interactive lab stations featuring research tutorials and experiments with foundation scientists Umesh Deshmukh, Ph.D., Mike Kinter, Ph.D., Courtney Montgomery, Ph.D., Wan Hee Yoon, Ph.D., and Rheal Towner, Ph.D., covering a broad range of the foundation’s ongoing research projects.
“It’s so wonderful to come back here to the place that took care of my late mother,” said Beale, an Oklahoma City resident. “It’s wonderful to see how much this place has grown and how it impacts people across the globe in really profound ways. Research that will maybe save your life one day is coming out of Oklahoma, and that’s special.”
Vater, an Oklahoma City resident and donor since 2012, echoed the sentiment. Vater also recently toured the facility with a group of residents from Epworth Villa.
“This is such a nice night, and it was delightful to be recognized,” said Vater. “We all give gifts for our own personal reasons, and OMRF is certainly deserving. We can see our donations are being used the right way. They are doing fascinating work.”
Each year OMRF welcomes a new class of Loyal Donors, who have been giving to OMRF for at least five years. The event is held to celebrate and recognize the difference they’ve made in helping others live longer, healthier lives.
“Disease touches every one of our lives in some form or fashion,” said Carl. “This group has chosen to step up and fight back against disease. I couldn’t have asked for a better event, and I look forward to building on it and showing our loyal supporters just how much we appreciate what they do for OMRF.”
Protecting moms from autoimmune disease
Whether your Mother’s Day tradition is serving breakfast in bed, treating her to a spa day, or heading to a movie, the most important part is spending time with mom.
But while we celebrate mothers, scientists at OMRF are working to protect them. Specifically, they’re trying to stop autoimmune diseases, conditions which disproportionately strike women.
Lupus, rheumatoid arthritis and multiple sclerosis are some of the disorders in which the immune system becomes unbalanced and attacks the body. All told, the diseases affect an estimated 25 million Americans.
“Almost all of the 80-plus autoimmune diseases we know are more common in women than men,” said OMRF immunologist Hal Scofield, M.D. “For example, Sjögren’s syndrome makes the body attack its own moisture-producing glands, and it occurs in women at a 9-to-1 ratio over men. Recent studies we’ve done may offer clues as to why it is so female-slanted.”
In a 2016 study, Scofield and his research team found that the diseases may not actually be based on gender—but on how many X chromosomes a person has. “When it comes to understanding the gender bias of autoimmune diseases, X might literally mark the spot,” Scofield said.
Chromosomes determine the biggest difference between males and females genetically. Each person typically has one pair of sex chromosomes per cell. Females have two X chromosomes, while males have one X and one Y.
Scofield said this avenue of research could lead to the discovery of pathways that could be more effectively treated by drugs to reduce the risk of developing these diseases or helping to better manage symptoms.
One way OMRF is already actively helping protect women from autoimmune disease is with the SMILE trial, the world’s first lupus prevention study.
The study launched late last year and is still actively recruiting new participants.
In the trial, researchers seek to identify individuals at high risk for developing lupus and treat them with an immune-modifying medication before they ever transition into the disease. The goal is to delay the onset of lupus, lessen its symptoms and potentially prevent it altogether.
“As a physician, I find this trial incredibly important because I have seen the damage and destruction that happens with lupus,” said OMRF Vice President of Clinical Affairs Judith James, M.D., Ph.D., who launched the project.
James said the ultimate goal is to prevent the disease from ever happening. But even if an individual still transitions into lupus, early detection and getting treatment started before the damage is done can mitigate the potential damage and improve outcomes.
“I think we have opened the door to understanding why there’s a sex bias or gender bias in autoimmunity,” said Scofield. “It could lead to new targeted therapies for autoimmune diseases that could result in longer lives for our sisters, wives, daughters and, of course, our mothers.”
Oklahoma researchers solve a genetic mystery—and save a teen’s life
A rambunctious kid with big brown eyes, Xander Auld liked to crack jokes and goof around with his friends. He loved sports and spent lots of time on the baseball diamond, football field and basketball court. He seemed like a healthy, happy, well-adapted child.
Still, his parents worried.
At the age of 1, Xander had been diagnosed with abnormally high levels of red blood cells, along with elevated blood pressure. A CT scan soon revealed another symptom: small growths, or “micro-cysts,” on his kidneys, pancreas and stomach.
His physicians could not find a cause for the symptoms. They prescribed medication to control his blood pressure and regular phlebotomies to keep Xander’s red-cell levels down. For more than a decade, he saw doctor after doctor, all to no avail. Over time, said his mother, Felicia Gamble, “It just became a part of life.”
Eventually, his case was referred to Klaas Wierenga, M.D., who holds the McLaughlin Family Chair in Genetics at the University of Oklahoma College of Medicine. After a battery of tests failed to cast any light on Xander’s condition, Wierenga turned to Patrick Gaffney, M.D., a genetics researcher at OMRF.
The best hope, the two researchers decided, was for Gaffney to use the DNA sequencing technology in his lab at OMRF to analyze Xander and all of his direct family members. That way, they could identify any potential genetic differences between him and his family, none of whom shared his symptoms.
For Xander, who was 13 at the time, one more test was no big deal. Not so for his younger brother, Landon. When the 10-year-old went to Wierenga’s office—along with his parents, Xander and his oldest brother, Isaiah—“he was scared,” said Gamble. Still, knowing it could help his brother, he bravely allowed Wierenga to extract blood from his arm.
Studying the results of a genetic sequence can be like trying to examine individual flakes in a snowdrift. While the test narrows the analysis to two percent of the human genome, that still leaves almost 30 million letters of DNA to analyze. “We looked at data for a long time and made very little progress,” says Wierenga.
But one night, a particular piece of data—a gene—caught Wierenga’s eye. “I knew this gene,” he said. “It’s associated with renal-cell carcinoma,” a malignant cancer of the kidney. Xander’s copy of this gene was mutated.
Doctors ordered an MRI, which revealed a golf-ball-sized tumor in Xander’s right kidney. Eleven days later, OU urologists Dominic Frimberger, M.D., and Mohammad Ramadan, M.D., removed the kidney. Happily, there was no sign the cancer had spread.
When Xander awakened, he was groggy from the anesthesia and in a good deal of pain. Still, the first words he said to his parents were, “Will you please tell the doctors thank you?”
Xander had imagined that recovery would be seamless. “He thought he was going to eat Buffalo Wild Wings right after surgery,” said his father, Matt Auld. “That didn’t happen.” Still, he was able to leave the hospital after two days. Three weeks later, he was back at school.
He underwent a single phlebotomy after surgery. When doctors did follow-up testing, his red-blood-cell count had decreased to a normal level. And it’s remained there ever since—without a single phlebotomy.
Similarly, after a few months, Xander’s blood pressure dropped. It fell so much that his doctors took him off all blood pressure medications.
Since that time, Xander has grown several inches and put on 20 pounds or so. He’ll turn 15 on Sunday, and he’s finishing up his freshman year at Yukon High School. Like his older brother, he joined the swimming team.
Most importantly, the cancer has shown no signs of returning.
The discovery of the mutation and the ensuing surgery, Gamble said, have been “life-changing. I am so thankful for this research.
“It could have been really bad if they didn’t catch it when they did.”
New shingles vaccine is a must
If you’ve ever had chicken pox, you already have the shingles virus hiding in your body.
But thanks to the development of a new vaccine, you may be able to completely avoid shingles for good, said OMRF immunologist Eliza Chakravarty, M.D.
The shingles virus is a painful, blistering skin rash that usually presents itself in one wide strip across the body, causing intense pain and often accompanied by flu-like symptoms.
“If that sounds bad, it can get even worse,” said Chakravarty. “Shingles can also bring on a complication called post-herpetic neuralgia, which can cause an excruciating, stabbing nerve pain where the original rash occurred. This can last for months or even years.”
But our ability to protect ourselves just got a lot better. In October 2017, the FDA approved the new shingles vaccine called Shingrix, and it’s better than the old vaccine, Zostavax, in virtually every way, said Chakravarty.
But what makes it better?
First off, said Chakravarty, Shingrix is made in a lab from proteins and contains no actual shingles virus. Zostavax, however, is a live attenuated virus, meaning it is made from a mutant version of the virus and carries a theoretical concern of causing shingles in certain situations.
“So like a flu shot or pneumonia vaccination, there is no live virus whatsoever in Shingrix. So it eliminates all worry for people worried about the safety of the vaccine,” said Chakravarty.
Another benefit of the vaccine coming from proteins is that it makes Shingrix safe for individuals with weakened immune systems, autoimmune diseases, and certain cancers, and other people who could not previously get vaccinated.
So not only is the new vaccine itself safer, said Chakravarty, Shingrix is also considerably better at protecting you from a shingles outbreak.
“Shingrix has been shown to be up to 90 percent effective at preventing shingles compared to about 50 to 60 percent for Zostavax,” she said. “That’s a huge win right there.”
And the benefits continue. The FDA also approved lowering the recommended age for the vaccine from 60 to 50, allowing people to receive better protection earlier.
If you’re 50 or older, getting this new vaccine is a no-brainer. And that includes people who have already received the old vaccine and individuals who have already had shingles.
“I think this vaccine will have a profound impact. Almost nobody dies from shingles, but it is truly miserable,” said Chakravarty. “This is safe, affordable and has a high likelihood of protecting you from a devastating few weeks or even years of pain.”
Golden years: OMRF gives tips on aging gracefully
Aging is inevitable, but it doesn’t have to be miserable.
The Aging and Metabolism Research Program at OMRF takes a comprehensive approach to addressing diseases of aging, looking at everything from vision loss to arthritis to age-related muscle loss.
Their goal, says program chair Holly Van Remmen, Ph.D., is “not just adding years to your life, but also adding life to your years.”
While research and medicine are making strides in improving health as people age, a lot of the burden falls on the shoulders of the individual. So here are a few tips from aging experts for making your golden years truly golden.
1. Move it
Exercise is crucial at every age. Unfortunately this is one thing many of us forego in favor of literally anything else.
Research shows even 30 minutes of exercise daily not only helps you avoid packing on the pounds, it also lowers blood pressure, strengthens bones and improves mood.
“From a muscle perspective, which is my primary area of expertise, this is one that can have a cascade of effects, either positive or negative,” said Van Remmen. “It can make or break your quality of life.”
Small amounts of weight training have been shown to benefit older people, she said. It helps maintain muscle mass over time and improves bone health. “All these things center around strength and mobility,” she said. “They also improve balance, and that can help you avoid falls and injuries.”
And you don’t need to develop bulging biceps to see benefits from weight training. Van Remmen suggests doing what you can do safely, from using light hand weights to resistance bands. Even just walking to the mailbox, taking the stairs or watering plants can help preserve your mobility and balance over time.
2. Focus on food
It’s no secret that obesity has a severe negative impact on health in a variety of ways. Heart disease alone kills 800,000 Americans annually and is a leading killer in Oklahoma. It can also lead to type 2 diabetes and contribute to osteoarthritis.
On the other side of the coin, malnutrition is also an issue in our aging population, said OMRF President Stephen Prescott, M.D. As people age, they tend to have relatively poor appetites as some of their senses dim. Prescott stresses the importance of eating adequate protein— 45 grams of protein for women and 55 grams for men—to help your body recover from wear and tear and maintain muscle mass.
“Shakes like those made by Ensure or Boost can help seniors maintain a healthy weight, said Prescott. “They aren’t a magic solution and they don’t replace nutrition-rich whole foods, but they can help.”
3. Brain gains
While physical exercise is important, exercising your brain is also valuable. Scientists increasingly believe it is wise to read, work puzzles, play games and socialize to help improve memory and keep the brain healthy and perhaps delay the onset of Alzheimer’s and other forms of dementia.
Alzheimer’s is the fifth-leading cause of death in Americans over the age of 65. It is the most common form of dementia, accounting for 60-80 percent of all cases, according to the Alzheimer’s Association.
“Don’t let your brain stagnate,” Van Remmen said. “Studies show that people age more successfully when they engage with others and stay active mentally. Whether that means taking part in bridge club, bingo night or church groups or just picking up a good book, do whatever suits you best.”
Spring allergies take toll on Oklahomans
Springtime is beautiful in the Sooner State, but it can also be brutal if you suffer from allergies.
Oklahoma City and Tulsa again placed among the worst cities in America for springtime allergies, ranking ninth and 40th, respectively in the new 2018 list from the Asthma and Allergy Foundation of America.
Oklahoma mixes the usual suspects—pollen, dust and mold—with its constantly swirling winds to create a perfect storm for your immune system to be tricked into making you miserable.
“Your immune system protects you from dangerous invaders like the flu, strep throat and other viruses by recognizing and attacking these invaders while ignoring what is safe and normal,” said Oklahoma Medical Research Foundation immunologist Eliza Chakravarty, M.D. “When the flu or a virus arrives, the immune system mounts an attack. In the case of allergies, though, your body mounts an attack against mostly harmless substances.”
So while there is nothing inherently dangerous about pollen, your immune system may see it as a threat anyway.
When an allergen enters the body, the immune system mistakenly thinks it’s under attack and responds by making antibodies. The antibodies surround the allergens and bind to them, releasing substances called histamines into the system.
Histamines interact with the nasal mucous membrane, triggering an allergic response that includes symptoms like watery eyes, runny nose, inflammation, sneezing and congestion.
“The bad news is that these symptoms are aggravating and annoying. The good news is they aren’t usually dangerous,” said Chakravarty.
While there is no cures for allergies, there are effective ways to mitigate them. Chakravarty said antihistamines like Allegra, Claritin or Zyrtec are still great options to manage symptoms.
Antihistamines don’t stop the body’s inappropriate reaction to the allergens, but they do block the action of the histamines. This saves you from the itchy eyes and runny nose.
Over-the-counter nasal sprays that contain low doses of steroids can also help relieve inflammation in the nasal passages.
“We’d love to develop therapies that will tell your immune system to relax when it’s just pollen or dust, but until then, those of you with serious allergies should limit time outdoors, minimize dust in the home and find an allergy medication that works for you,” said Chakravarty. “Even though they are annoying, the silver lining is that allergies are mostly harmless.”
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