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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.” |
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 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.”
Lots o’ luck: How the shamrock gets its shape
The four-leaf clover has long been considered a symbol of good luck.
While it’s unknown where the tradition originated, four-leaf clovers are most commonly associated with Ireland because of the island’s high rate of producing the rare four-leaf variety. It has since become a symbol for the St. Patrick’s Day holiday.
The four leaves are said to represent hope, faith, love and luck. But they also represent something else: genetic mutation.
“Believe it or not, four-leaf clovers aren’t a specific type of clover. These lucky charms actually are mutants,” said OMRF scientist Courtney Montgomery, Ph.D.
Clovers bearing four leaves are rare because they are genetically mutated three-leaf clovers. The four-leaf variety only occurs once in approximately every 5,000 three-leaf clovers. Reported instances of five-leaf and six-leaf clovers are all mutants of the three-leaf variety.
“These mutations occur because of changes in the sequences of the plant’s DNA, or changes in gene structure,” said Montgomery.
And clovers aren’t alone. Even humans undergo mutations of varying degrees. To understand these mutations and how they occur in everything from a clover to a human, it’s important to know a little about genetics.
“Think of your genetic makeup like a book,” she said. “Your genome is the whole book, and the proteins are sentences. The base pairs that make up the DNA are the letters. But the genetic alphabet only has four letters (or chemicals) to create the words that make up everything in the book.”
Those four chemicals—adenine, thymine, cytosine and guanine—comprise the story of you, your neighbor or even a four-leaf clover. Used in countless combinations, sequences and orders, they result in a book you’d struggle to read, with about 3 billion base pairs in a single set of human DNA.
“These A, T, G, C sequences in genes determine things like hair color, height, susceptibility to certain diseases and much more,” said Montgomery, who studies genetics on the human front in autoimmune diseases like lupus and sarcoidosis.
A single change in the order or number of these chemicals can result in mutations, and the changes are permanent. Certain mutations can even have observable consequences, like a fourth leaf on a shamrock.
While they make us unique, sometimes these changes can have negative consequences, contributing to diseases like asthma, heart disease and cancer, all of which have a genetic component. Sickle cell anemia is a rare disease almost exclusively controlled by genetic mutations.
“We all have mutations in our DNA, a lot of them actually,” Montgomery said. “But we tend to categorize them based on whether or not they result in a change we can see. But some can be completely benign and have no health consequences of any kind.”
Researchers are just beginning to truly understand mutations, because the science of genetic sequencing has only recently progressed to the point where DNA can be tested against parents and other family members, she said.
“These advancements could lead to a wide range of new discoveries by helping us better understand the role genetic mutations play in human health,” she said. “When we find those answers, the research could bring all of us plenty of good luck for the future.”
OMRF scientist selected for national sarcoidosis fellowship
OMRF scientist Lori Garman, Ph.D., has been selected as one of two national recipients of the Foundation for Sarcoidosis Research Fellowship Program Award.
The Foundation for Sarcoidosis Research is the leading nonprofit organization in the U.S. dedicated to the rare autoimmune condition. This award is tailored to support the transition process for scientists and doctors early in their careers studying and treating the condition.
Sarcoidosis is a disease where cells in the immune system that cause inflammation can overreact and cluster together to form tiny lumps called granulomas. If too many of these granulomas form in a single organ, this can cause the organ to malfunction or even fail. These granulomas can form in the eyes, liver, skin and brain and most often are found in the lungs.
The two-year, $250,000 grant will help pay for Garman’s salary, laboratory supplies, equipment and fund a portion of her research. This fellowship is mentored by OMRF scientist Courtney Montgomery, Ph.D., who said that this program is an excellent way to bring talented investigators into the field of sarcoidosis research.
“Having worked in sarcoidosis research for over a decade and witnessed the progress we are making, it is critical to future success to bring new, bright scientists into the field,” said Montgomery. “Lori is indeed such a scientist, and I am happy to be her mentor as she transitions her career in this way.”
Garman’s research centers on the complicated genetic basis of the disease, specifically how genetic and environmental factors affect immune cells that might predispose individuals to sarcoidosis.
To do this, Garman will look at specific genes to see how they react with certain environmental factors, including specific infections and viruses, which may interact and contribute to the formation of sarcoidosis.
“Immune cells in a healthy person are controlled, so they don’t interact too much with your own body,” Garman said. “But genes in sarcoidosis patients may be less suppressed, allowing the immune system to react against itself in damaging ways. I am looking at how this process contributes to sarcoidosis, because we are still trying to nail down the specific causes of this complex disease.”
Garman will study these interactions on a cell-by-cell basis at 5,000 cells per individual to determine how these genes are expressed and how these cells factor into the disease.
Garman was also instrumental in the November launch of OMRF’s new Sarcoidosis Research Unit, which was created to collect sample donations from patients to work toward a better understanding of the underlying biology of the condition.
“I am incredibly grateful for this award. It provides an amazing opportunity for me to do meaningful research that can have a positive impact for people suffering from this condition,” she said.
OMRF seeks participants as it launches new sarcoidosis unit
OMRF is seeking volunteers who have been diagnosed with sarcoidosis, as well as healthy individuals, to participate in sample donations for OMRF’s new Sarcoidosis Research Unit.
The unit is the first of its kind in the state and the only one in the region.
Sarcoidosis is a rare disease where cells in the immune system that cause inflammation overreact and cluster together to form tiny lumps called granulomas. If too many of these granulomas form in a single organ, this can cause the organ to malfunction or even fail. These granulomas can form in the eyes, liver, skin and brain and most often are found in the lungs.
African-American and European American individuals who have been diagnosed with sarcoidosis, as well as healthy African-American and European American people with no history of autoimmune disease, are eligible to participate.
OMRF scientist and Sarcoidosis Unit Director Courtney Montgomery, Ph.D., said sarcoidosis strikes 39 in 100,000 African Americans, versus only 5 in 100,000 Caucasians. A recent study showed that the mortality rate, particularly among women, is nearing 7 percent.
This disease is poorly understood currently but is thought to involve both genes and environmental factors, Montgomery said. OMRF is working to identify the genetic factors that lead to the disease in order to improve diagnosis, treatment and disease outcomes. “To achieve these goals, we need participants to help us learn more about sarcoidosis,” she said.
Participants will undergo a screening process, complete questionnaires, and donate a small blood sample to be used for research. Participants must also provide consent to review medical records and request previous biopsies related to the disease.
“We are thrilled to be able to offer this option to Oklahomans,” said Montgomery, who has studied the disease for nearly 20 years. “Sarcoidosis patients are often misdiagnosed or undiagnosed. By coming here and allowing us to learn from them, they can play a key role in helping us understand the underlying biology of the condition.”
Montgomery said by having an active research team, researchers can take discoveries they’ve made and translate them into something clinically meaningful. She also said the new facility is intended to serve as a long-term resource to the public.
If you are interested in participating or would like more information about donating to the Sarcoidosis Research Unit, please call toll-free at 800-605-7447. Participants will also receive $20 per visit.
AHA, OMRF host STEM event for teen girls
On Sunday, the American Heart Association hosted a special STEM education program for its 2017-18 class of Sweethearts at OMRF.
Women representing a variety of science, technology, engineering and math fields met face-to-face with participants in small groups before coming together in a general session. Panelists fielded questions from attendees and further expanded on their personal experiences in the sciences, both in school and as they established their careers.
OMRF scientist Courtney Griffin, Ph.D., served as host for the event. Griffin has spent her career manipulating DNA, the encyclopedia of genetic information that is inside of each of our cells. In the lab, she edits DNA of laboratory mice so that she can understand the development and function of blood vessels in these animals. The AHA has funded her research for more than 20 years.
Other speakers were OMRF physician-scientist Eliza Chakravarty, M.D., OMRF statistical geneticist Courtney Montgomery, Ph.D., Angela Robinson, Senior Business Manager at The Boeing Company, and Usha Turner, Director of Environmental Affairs at OGE Energy Corp.
Each of the women described the nature of her education and career path and her current work. They also told what they would like to have said to themselves at the age of 16 about perseverance, enlisting mentors and goal-setting.
“This STEM event is exciting for me, because it unifies the strengths of AHA and OMRF in promoting science and math career options to young women,” said Griffin. “I might not have considered becoming a scientist if I hadn’t met an influential female scientific role model when I was a teenager. I hope I can similarly inspire young women to consider science as a rewarding and creative career option.”
AHA’s Sweetheart Program provides educational and social programs for the girls during the school year. Activities are designed to groom the Sweethearts as future heart health advocates. The girls are presented at the annual Heart Ball in February.
“The girls were eager to know what it’s like to work in male-dominated fields and how STEM leaders are able to juggle family life along with such demanding careers,” said American Heart Association Executive Director Debbie Hite Stewart. “The event really seemed to provide an opportunity for the students to think about their futures and what direction they may want to go as they near high school graduation.”
Can you control your family’s genetic destiny?
As the parent of two children, Courtney Griffin, Ph.D., is well aware that the choices she and her husband make will have a profound impact on their daughters’ lives.
But Griffin is also a scientist at the Oklahoma Medical Research Foundation who studies the emerging field of epigenetics. And through her research in this area, she is learning that the decisions we make as parents—what we feed our children, how much attention we give them as infants—may impact more than just our children, but also the genetic destinies of our descendants for generations to come.
Epigenetics are chemical changes to the genome that affect how DNA is packaged and expressed without affecting the underlying genetic sequence.
“Epigenetics works like a watermark on top of genes,” said Griffin. “If you imagine your genetic makeup as a well-oiled machine, epigenetics are like the rust that settles on it and leaves a surface coating. This can muck things up, suppressing genes that need to work or turning on genes that are meant to be quiet.”
Scientists have determined that these marks can form as a result of the foods we eat, the toxins we ingest or even the stressful events we experience. And that they can persist for generations in some species.
“The real news with epigenetics is that these actions can theoretically affect more than just you and your children, but also your great grandchildren, great-grandchildren and beyond,” said Griffin.
A geneticist by trade, Griffin has spent her career manipulating DNA, the encyclopedia of genetic information that is inside of each of our cells. Griffin edits DNA of laboratory mice so that she can understand the development and function of blood vessels in these animals. She said her experience has shown her that epigenetic marks really can serve to reprogram genes’ behavior.
“Anything that genetics controls, which is essentially everything about us, can be altered,” said Griffin. “It comes back to how the marks are read by proteins in the cell. Any extra variable changes what they read, and these variables can be introduced by bad lifestyle habits.”
Luckily, said Griffin, research suggests these epigenetic marks don’t have to be permanently etched onto your DNA. “It appears these marks are quite malleable in humans, and making healthy choices like eating a better diet or reducing stress can make a difference,” she said.
“To me, it’s profound and empowering that we can influence how our genes work through the choices we make,” she said. “It gives us yet another reason to live a healthy life and make smart choices, because it doesn’t just affect us.”
Findings yield new clues to puzzling autoimmune disease
Led by researchers at OMRF, an international coalition of scientists and physicians has discovered a new genetic risk factor that may predispose certain individuals to a debilitating condition known as Sjögren’s syndrome.
Sjögren’s is an “autoimmune” disease, a family of illnesses in which the body destroys its own cells. In Sjögren’s, immune cells attack moisture-producing glands, leading to painful dryness and decreased ability to produce tears or saliva. The disease may affect as many as 4 million Americans, according to the Sjögren’s Syndrome Foundation.
Common symptoms include severe dry eyes and dry mouth, as well as fatigue, arthritis and memory problems. While its causes are not fully understood, environmental triggers, such as viral infections, are believed to contribute to the development of Sjögren’s in individuals who carry certain genetic risk factors for the disease.
In this new study, OMRF scientist Kathy Sivils, Ph.D. and her colleagues identified a strong association between a variant in a gene called OAS1 and susceptibility to Sjögren’s. This variant may provide valuable insight into the genetic basis of Sjögren’s, as well as other autoimmune conditions with similar triggers.
“This gene was of particular interest to us, because it plays a major role in how individuals respond to viral infections. Previous studies had shown that if a person carries this variant, they may be more susceptible to certain viruses like West Nile and hepatitis C,” said Sivils.
“There was very little evidence for a connection to autoimmune disease prior to our study. Firmly establishing this new association with Sjögren’s then led us to look at the gene’s function in more detail,” said OMRF scientist and co-leader of the project, Christopher Lessard, Ph.D.
Scientists found that individuals with this genetic variant produce alternative forms of OAS1 that appear to lose normal function, said Sivils, and that can result in an increased susceptibility to viruses, as well as diseases like Sjögren’s. The discovery could allow researchers to test for the variant to identify people at higher risk for the disease.
“If we can get out ahead of the disease, it might help lessen the severe damage that can occur in salivary glands and other organs,” Sivils said. “Early diagnosis and proper treatment are crucial, and discoveries like this one may give researchers and healthcare professionals more to work with as they look for clues to this perplexing disease.”
Sivils conducted the research as part of larger coalition known as the Sjogren’s Genetics Network, or SGENE. The network includes more than 60 scientists and physicians from the U.S., England, France, Norway, Sweden, Germany, Colombia, the Philippines and Australia. The findings were published in the journal PLOS Genetics.
“On behalf of Sjögren’s patients, the Sjögren’s Syndrome Foundation applauds OMRF for its commitment to finding the many unanswered questions about the disease,” said SSF CEO Steven Taylor. “Drs. Sivils and Lessard, along with their OMRF colleagues, continue to leave their mark in advancing Sjögren’s research, and patients worldwide will benefit from their hard work.”
Other OMRF researchers who contributed to the findings were He Li, Ph.D., Astrid Rasmussen, M.D., Hal Scofield, M.D., Judith James, M.D., Ph.D., Darise Farris, Ph.D., Patrick Gaffney, M.D., Courtney Montgomery, Ph.D., Susan Kovats, Ph.D., Indra Adrianto, Ph.D., Joel Guthridge, Ph.D., Ph.D., John Ice, M.D., Tove Reksten, Jennifer Kelly, Kiely Grundahl, Stuart Glenn, Adam Adler and Sean Turner.
National Institutes of Health grants that contributed to this research include P50 AR0608040, 1R01 AR065953, 5RC2 AR058959 and 5P30 AR053482 from the National Institute of Arthritis and Musculoskeletal and Skin Disease; 5R01 DE015223, 1R01 DE018209 and 5R01 DE018209 from the National Institute of Dental and Craniofacial Research; 5U19 AI082714 and U19 AI056363, 5P01 AI083194, 1U01 AI101934 from the National Institute of Allergy and Infectious Diseases; and 8P20 GM103456, 1P30 GM110766, U54 GM104938, 5P30 GM103510 from the National Institute of General Medical Sciences.
Additional funds for OMRF’s research were provided by the American College of Rheumatology Research and Education Foundation/Abbott Health Professional Graduate Student Preceptorship Award 2009, the Sjögren’s Syndrome Foundation and the Phileona Foundation.
Military academy students get hands-on lab experience at OMRF
Three U.S. military academy students have completed a crash course in biomedical research at OMRF through the John H. Saxon Service Academy Summer Research Program.
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 eighth annual program.
John Saxon III, M.D., a Muskogee physician and OMRF board member since 2000, established the program to honor his father, a West Point graduate who taught for five years at the U.S. Air Force Academy and was a career Air Force pilot before passing away in 1996.
The Saxon program is designed to provide military academy students with an opportunity to work side-by-side with OMRF’s senior scientists.
Matthew Lerdahl, a Coon Rapids, Minn., native and cadet captain first class in the U.S. Air Force, worked in the lab of Roberto Pezza, Ph.D., studying cell division.
Lerdahl, a biology major, specifically worked on what happens when cell division goes wrong in mitosis, which can result in disorders like Down syndrome and is implicated in certain cancers.
“This experience has been even more intense than I thought, and that’s a great thing. It’s very hands-on and the mentors are super helpful but also give you the freedom to make mistakes and learn on your own,” said Lerdahl. “It made me a better scientist and researcher. The environment here is just phenomenal.”
Erin McShane, a battalion sergeant major at the U.S. Naval Academy, is a chemistry major who was assigned to the lab of Ken Humphries, Ph.D., where she worked with an enzyme called PFK2. This is important because it is under-expressed in people with diabetes. It could provide a clue as to why diabetics can’t properly metabolize glucose.
“This project has been fascinating and a truly unique experience. I have an interest in serving in the Navy’s medical corps, and this has provided invaluable exposure to what medical research looks like up close,” she said. “We have sent someone from the academy here for several years, and I am thrilled to have had this amazing opportunity.”
Yuma, Ariz., native and Naval Academy midshipman second class Jocelyn Rodriguez worked under the guidance of Courtney Griffin, Ph.D., where she studied the formation of the vasculature, specifically during development of embryos. Rodriguez, who studies chemistry, said understanding how vessels work is important not only for embryonic development but also during the development of a tumor. Understanding how to disrupt the process could lead to new ways to slow or stop tumor growth.
“I have an interest in becoming a medical officer, and this opportunity has been great for my future,” she said. “It’s fun to pick the scientists’ brains to see if I want to do research or be more on the clinical side of things. It’s also great to see the leadership styles here at OMRF. Dr. Griffin is phenomenal and you can really see people love to come to work every day in her lab. It’s inspiring.”
