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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.”

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.

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.

OMRF hosts 2018 Loyal Donors reception

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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

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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

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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.”

Mothers’ Clubs continue legacy of support for OMRF

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Nobody has your back quite like your mother. OMRF has enjoyed that kind of support for 62 years.

On April 13, the Oklahoma Association of Mothers’ Clubs donated $1,632 to the Oklahoma City-based nonprofit research institute, presenting a check at their annual banquet at the Skirvin Hotel in downtown Oklahoma City.

With the more recent gift, it brings the Mothers’ Clubs total contributions to OMRF to more than $125,553.

The donations go to research for cancer, heart disease and autoimmune disease research. It has even funded the purchase of lab supplies and paid for summer scholarships for state high school and college students.

Each year, OAMC members across the state raise money for OMRF by holding bake sales, golf tournaments, 5k runs, and father-daughter dances.

“We are so fortunate to have their ongoing commitment. This dedication has truly helped lead to discoveries that make a difference in the lives of many,” said OMRF development stewardship coordinator Marissa Valdez. “Words cannot describe how grateful we are for their friendship and their passion to build a stronger, healthier community for all of us.”

The association, founded in 1940, is made up of Mothers’ Clubs in the following Oklahoma cities:

  • Canton
  • Lexington
  • Fairview
  • Goldsby
  • Hennessey
  • Ponca City
  • Okeene
  • Purcell

Experts propose improving clinical trials for lupus

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An OMRF physician-scientist is spearheading a call for transformative changes in clinical trials for new lupus drugs. In a new paper Joan Merrill, M.D. led a large team of lupus specialists and treatment developers to detail approaches that could lead to new and effective drugs reaching hospitals and clinics.

“In a nutshell, the goal of the paper is to create a dramatic shift in how lupus clinical trials are conducted so effective treatments can stand a chance to succeed,” said Merrill, Director of Clinical Projects in the Arthritis and Clinical Immunology Program at OMRF, who also serves as the Lupus Foundation of America’s Chief Advisor of Clinical Development.

The paper addresses long-standing barriers that have limited the development of new treatments for lupus. Only one new drug, belimumab, has been approved since the 1950s.

“I have been involved in more than 30 failed clinical trials since the 1990s, and they did not all need to fail. Because of the way things have been set up, a lot of these drugs will never be made available even though they might have been effective,” said Merrill.

Lupus is a chronic autoimmune disease that can cause unpredictable flares of inflammation affecting almost any organ in the body. While the disease can be relatively mild in some people, it can become serious and even fatal for others, causing serious damage to the brain, heart, kidneys or lungs.

According to the LFA, more than 1.5 million Americans have one or more form of lupus, which primarily strikes women. The standard of care relies on trial and error, primarily using treatments borrowed from other illnesses that have not been properly studied in lupus.

In the paper, Merrill and her colleagues propose making it possible to test more treatments by decreasing the size of trials. This can be accomplished through designs that increase the differences that can be detected when effective treatments are given, while reducing false impact from ineffective agents. The specific recommendations about how to do this are based on the analysis of many past, disappointing studies in lupus, and include the evaluation of more clear-cut disease manifestations, more stringent endpoints and use of current scientific advances to help select patients most likely to benefit from a specific therapy.

“If you take these ideas and apply them to clinical trials, we will be able to interpret the data better,” said Merrill. “This could lead to more approvals of effective drugs and will prevent ineffective drugs from succeeding. That would be huge, because our patients need safer and more effective treatments.”

The group also urged a community-wide effort to make trials available to patients with more types of lupus and to more minority patients, who, when left out of trials are also left out of access to new treatments that could work for them.

Merrill authored the paper, which appeared in the journal Lupus Science & Medicine, with substantial input from Susan Manzi, M.D., M.P.H., Chair of the Medicine Institute at Allegheny Health Network and Medical Director of the Lupus Foundation of America, and Victoria P. Werth, M.D., Professor of Dermatology and Medicine at the University of Pennsylvania School of Medicine, as well as a large group of leading lupus clinicians and trialists, and advice from biopharmaceutical experts. The Lupus Foundation of America will be presenting the findings of this paper to the FDA in the coming months.

At OMRF, Dr. Merrill works closely with Dr. Judith James, Head of the Arthritis & Clinical Immunology Program, in designing trials for lupus that are linked to complex immunologic profiling of the patients.

“We are working on small pilot projects to bring lupus treatment kicking and screaming into the 21st century,” she said.

Discovery could explain cell division errors in cancer

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Scientists at OMRF have discovered a way in which cells duplicate themselves accurately and completely.

The new findings provide a better understanding of how cells replicate, and it could help outline how and why this process goes wrong in cancer.

The genome is the complete set of genes or genetic material in an organism. Each cell carries the full set of genes from mom and dad, so every time a cell divides—which happens not only as we grow, but also throughout our lives as our cells repair and regenerate themselves—the genome must be accurately and completely duplicated. The process of genome duplication is called DNA replication.

DNA replication is extremely complex, said OMRF scientist Christopher Sansam, Ph.D. So, it’s not surprising that it goes awry, and the results can be devastating. Mistakes in DNA replication can lead to cancer.

“The best way to think about the genome is as an instruction manual—a really giant one—that gets copied every time a cell divides. This takes tens of thousands of cellular photocopiers to achieve,” said Sansam.

These copiers, said Sansam, have to ensure genetic information is replicated completely and without error. This is a key issue in cancer, a disease caused by damage to genetic material.

In his lab at OMRF, Sansam and his research team studied what prompted the process of DNA replication and where in the genome that process began.

Their research revealed a novel function for a type of cellular proteins called BET proteins and established an interaction between them and a protein essential in initiating DNA replication called TICRR. This point of interaction appears to be crucial in the identification of genetic marks that serve as a starting point for the process.

Sansam said this finding will allow for researchers to begin working toward new potential drug targets that can zero in on cancers at the origin point of this cell division process.

“In the early progression of cancer this copying of the genome goes awry, but we didn’t know how this happens,” said Sansam. “Now that we understand how these marks influence replication, we can look to see if that contributes to cancer formation. This could prove to be a big piece of the puzzle.”

The findings were published in the journal Genes & Development.

This work was supported by grant Nos. 5P20GM103636 and 1R01GM121703 from the National Institute of General Medical Sciences, a part of the National Institutes of Health. Additional funding was provided by a Health Research Program Award from the Oklahoma Center for the Advancement of Science and Technology (OCAST). OMRF researchers Courtney Sansam, Ph.D., Katarzyna Pietrzak, Maciej Kerlin, Blanka Majchrzycka, Jingrong Chen and Susannah Rankin, Ph.D., contributed to the findings.

OMRF honors Everest, five scientists

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At its annual honors and awards ceremony on Thursday, OMRF presented Christy Everest with its Board of Directors Distinguished Service Award.

Also at the ceremony, three researchers received scientific honors, and two others were named to endowed chairs.

Everest joined the OMRF board in 2008. In the ensuing decade, she has served on OMRF’s Executive, Development, Technology Ventures and Governance committees and co-chaired a fundraising effort that raised more than $10 million for cancer research at the foundation. She has also contributed considerable financial support for research and capital expansion projects through the Gaylord Foundation and personal giving. Everest’s father, the late Edward L. Gaylord, served as OMRF’s board chairman from 1983-1996.

“Christy Everest has been a tremendous advocate for medical research and OMRF,” said OMRF President Stephen Prescott, M.D. “OMRF is a better place because of her service.”

Also at the meeting, OMRF presented scientific honors to three researchers.

Darise Farris, Ph.D., received the Merrick Award for Outstanding Medical Research. Her work in the lab focuses on the roles of immune cells in autoimmune diseases, conditions in which the body mistakenly attacks its own cells and tissues.

Scott Plafker, Ph.D., was given the J. Donald & Patricia H. Capra Award for Scientific Achievement for his field-leading studies of vision loss. Last month, he received a four-year grant from the National Institutes of Health to investigate whether a compound found in leafy vegetables could protect against age-related macular degeneration.

Christopher Sansam, Ph.D., received the Fred Jones Award for Scientific Achievement for his innovative research on how DNA accurately copies itself during cell division, work that holds important implications for treating cancer and preventing birth defects.

Also at the meeting, a pair of OMRF scientists were named to endowed chair positions. Swapan Nath, Ph.D., was named the William H. & Rita Bell Chair in Biomedical Research. Nath is an internationally respected leader in the study of genetic risk factors for lupus and other autoimmune diseases.

Florea Lupu, Ph.D., was named the H. Allen & Mary K. Chapman Chair in Medical Research. He has been recognized for his seminal research in sepsis and blood clotting and is an authority in microscopy.

“I am incredibly proud of all our scientists who were honored,” said Prescott. “They deserve this recognition, and the work they are doing puts the value and impact of medical research on full display.”

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