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At its semiannual meeting on Thursday, OMRF named The Honorable Terence Kern to its board of directors, honored long-time director David Rainbolt and named Judith James, M.D., Ph.D. its first Vice President of Clinical Affairs. Judge Kern, of Tulsa, is a Senior Judge on the U.S. District Court for the Northern District of Oklahoma. A native of Clinton, Okla., Judge Kern graduated from Oklahoma State University and subsequently from the University of Oklahoma School of Law. A former Army reserve member and attorney at the Federal Trade Commission, he practiced as an attorney in Ardmore for 24 years before being named to the federal bench in 1994. He served as Chief Judge of the Northern District for seven years and took senior status in 2010. Last month, he was inducted into the OSU Hall of Fame. Rainbolt was presented with the OMRF Board of Directors Distinguished Service Award. Rainbolt, who is Chief Executive Officer of Bancfirst, joined OMRF’s board in 1994 and has served in numerous leadership roles during his 23-year tenure as an OMRF director. “David Rainbolt has been an ardent supporter of OMRF and our mission for many years,” said Prescott. “He has been actively engaged in all aspects of board service and has provided wise counsel and leadership that have proved invaluable to the foundation.” Also at the meeting, the foundation named Judith James, M.D., Ph.D., a physician-scientist, as Vice President of Clinical Affairs. In that role, she will oversee all clinical activities at the foundation, which treats and conducts clinical research projects involving thousands of patients suffering from lupus, rheumatoid arthritis and multiple sclerosis. A native of Pond Creek, Okla., James earned her M.D. and Ph.D. degrees from the University of Oklahoma Health Sciences Center and joined OMRF’s scientific staff in 1994. An internationally acclaimed researcher, she is best known for her work in the prediction and prevention of the autoimmune disease lupus. Her research has resulted in OMRF being named a National Institutes of Health Autoimmunity Center of Excellence, one of only 10 nationwide. She is chair of OMRF’s Arthritis and Clinical Immunology Research Program and holds the Lou C. Kerr Endowed Chair in Biomedical Research. “Dr. James is regarded by her peers worldwide as a pioneer in autoimmune disease prediction and treatment,” said Prescott. “She has helped expand OMRF’s clinical capabilities and assembled a stellar team of physicians dedicated to tackling some of the most puzzling and difficult-to-treat diseases. In her new role as Vice President of Clinical Affairs, she will continue to build synergy between the clinic and the research lab, which ultimately will benefit patients.” Two other OMRF researchers received special recognition at the meeting:
Finally, OMRF presented the Edward L. and Thelma Gaylord Prize for Scientific Achievement to Holly Van Remmen, Ph.D. The award is OMRF’s highest scientific prize, and it went to Van Remmen for her research on neurodegeneration and muscle loss in aging. The award is named for the late Edward L. Gaylord, who served on OMRF’s board for 30 years, and his wife, Thelma. The Gaylords’ daughter, Christy Everest, currently serves on the foundation’s board. Van Remmen earned her Ph.D. from the University of Texas Health Sciences Center, San Antonio, where she was a faculty member until joining OMRF in 2013. At OMRF, she leads the Aging & Metabolism Research Program and holds the G.T. Blankenship Chair in Aging Research. “Dr. Van Remmen is a tremendously hard worker and has a gift for fostering collaboration,” said Arlan Richardson, Ph.D., Van Remmen’s former mentor and now a professor at the University of Oklahoma Health Sciences Center. “She has grown into a noted leader in aging research.” |
Blood test identifies people at high risk for lupus
New research from OMRF will help physicians better identify blood relatives of lupus patients at risk for developing the disease.
Lupus is caused by the immune system becoming unbalanced, leading to the development of autoantibodies and chronic inflammation that can damage the body’s tissues and organs. The disease predominantly strikes women and healthy relatives of lupus patients have an increased risk of developing the autoimmune disease compared to the general population.
In their recently published paper, OMRF scientists Judith James, M.D., Ph.D., and Melissa Munroe, M.D., Ph.D., evaluated previously unaffected relatives of lupus patients. Of the 409 lupus relatives who agreed to participate in the follow-up study, on average 6.5 years from their last evaluation for lupus, they found that 11 percent—45 people—had since developed lupus.
“We have been very curious about why some family members go on to become lupus patients themselves while others stay healthy,” said James. “We know that family members have some shared genetic risk, but we want to identify who is the most at-risk.”
James and Munroe found that higher levels of specific inflammatory proteins in the blood predicted which subjects would develop the disease. On the other hand, family members who did not develop lupus had higher-functioning regulatory mechanisms in place that may have been protective.
“Although many relatives transitioned into lupus patients, we had far more, 89 percent, who stayed healthy,” said Munroe. “This research focused on trying to find blood markers that identify people, even seven years beforehand, who are going to become lupus patients.”
Based on the results of this study, which were published in the scientific journal Arthritis & Rheumatology, James and Munroe recommend that physicians test the relatives of lupus patients for the specific inflammatory proteins in their blood. For those who display higher levels of the proteins, they suggest referring them to a rheumatologist for a consultation and possible enrollment in clinical trials focused on preventing disease onset.
James and Munroe will be partnering with other lupus researchers to launch one such prevention trial at OMRF. Known as SMILE, the clinical trial will seek to identify individuals found to be at high-risk for lupus and treat them with an anti-inflammatory medication. The goal of the upcoming prevention trial is to delay the onset of lupus, lessen the symptoms of the disease, or potentially prevent it altogether.
“This kind of work is really expansive and new,” said James. “It gives us hope that we can better identify early markers for the development of lupus, but maybe even more importantly, that we can learn from the immune systems of family members who don’t get sick. This might tell us how we could retrain the immune system to keep people healthy.”
A native of Pond Creek, Okla., James earned her M.D. and Ph.D. degrees from the University of Oklahoma Health Sciences Center and joined OMRF’s scientific staff in 1994. A pioneer in the field of autoimmune disease prediction and holder of the Lou C. Kerr Chair in Biomedical Research at OMRF, her work has advanced scientists’ understanding of lupus and helped physicians delay disease onset in patients displaying early symptoms of lupus.
Munroe joined OMRF in 2010 from the University of Iowa. Her research focuses on developing and testing novel strategies for monitoring autoimmune diseases with the goal of mitigating or preventing further organ damage caused by these diseases.
Other OMRF staff members who contributed to this project were Joel Guthridge, Ph.D., Virginia Roberts, Tiny Powe, Tim Gross, Wade DeJager, Rebecka Bourn, Ph.D., and Angela Andersen, Ph.D.
The study was supported by the National Institute of Allergy, Immunology and Infectious Diseases (grant numbers U01AI101934, R01AI024717, U19AI082714), the National Institute of General Medical Sciences (grants U54GM104938, P30GM103510), and the National Institute of Arthritis, Musculoskeletal and Skin Diseases (grants P30AR053483, RC1AR058554, and U34AR067392). All of these are parts of the National Institutes of Health.
OMRF hosts national biotechnology forum
On Tuesday, 35 leading venture capitalists and biotechnology industry executives from across the country joined 95 state scientists and business leaders at the Oklahoma Medical Research Foundation at the 2017 OMRF BioVenture Forum.
The goal of the event was to explore the commercialization of technologies and encourage interaction between industry and with scientists in Oklahoma, as well as increase the visibility of the quality research underway at OMRF.
Visiting attendees represented some of the top names in the industry, including Pfizer, Merck, AstraZeneca, AbbVie, 5AM Ventures and Lilly Ventures.
“Many consider Oklahoma a fly-over state, so it can be difficult to get name recognition even though OMRF has been highly successful for a very long time,” said Manu Nair, OMRF’s Vice President of Technology Ventures, who organized the event. “When people think of Oklahoma, they think of oil and gas. We want them to see a biotech mecca here, as well.”
The keynote speech was delivered by Joseph Miletich, M.D, Ph.D., senior vice president of Discovery Research, Preclinical Sciences & Early Development at Merck Research Laboratories. Panel discussions covered a variety of topics, from current trends in industry and drug development and relationship dynamics in startups to diverse funding opportunities.
“It’s important to spend time with people in different venues to understand what’s important in different parts of the country,” said Miletich. “To come to Oklahoma and interact and hear about opportunities and perhaps share what I know, I think it’s useful for the goal all of us have: trying to create medicines that extend people’s quality and length of life.”
In addition to panel discussions, the day’s events included a tour of OMRF’s facilities, networking sessions and a reception with Oklahoma Governor Mary Fallin at the governor’s pavilion.
“When people think of Oklahoma, bioscience may not be the first word that comes to mind. But the bioscience sector has joined our heritage industries of energy and agriculture to become a major force in the state’s economy,” said Fallin. “The science here is cutting-edge, but we’re still a well-kept secret in the biotech world. That’s a combination that spells opportunity.”
Lijun Xia, M.D., Ph.D., program chair of OMRF’s Cardiovascular Biology Research Program, was one of many foundation scientists in attendance. Xia said that connections he made at OMRF’s first BioVenture Forum, which took place in 2015, helped him forge a research collaboration with an industry partner and that he hoped this year’s event would plant the seeds for further partnerships.
“As scientists, we typically do not openly interact with industry professionals,” said Xia. “So after interacting with people from biotech at this forum, we may learn the translational potential of our basic research and form collaborations to develop new tools for diagnosis and therapies. The potential is great, and it is important to bring people in to see what we do here.”
Nair said the objective of this year’s forum is to dig deeper into more specialized aspects of biopharma, investment business and technology development to showcase the biomedical research capabilities in Oklahoma and at OMRF. Discoveries incubated by OMRF’s Technology Ventures office have resulted in three drugs that received FDA approval and a diagnostic test currently available on the market.
“The goal of the forum was to spark commercialization by bringing in folks who have varying interests so we can get a broad spectrum of ideas and thoughts regarding tech commercialization and investment,” said Nair. “I think it was a success, and partnerships will blossom out of this as a result.”
No (April) foolin’: Five medical myths busted
For all the harmless gags April Fools’ Day brings, some hoaxes pull people’s legs year-round. When it comes to health myths, they range from silly to downright dangerous.
So, in honor of a day filled with hoaxes, scientists at OMRF are putting five medical myths to rest.
- We need 8 glasses of water a day
It’s true that in 1945, the Food and Nutrition Board recommended people should shoot for consuming 2.5 liters of water per day. But, said OMRF President Stephen Prescott, M.D., “What people don’t consider is that a lot of that is already contained in fruits, veggies, coffee and everything else we consume.”
In addition, individual fluid needs will vary a good deal based on people’s body mass and the weather conditions. So Prescott encourages people simply to use common sense and let their thirst be their guide. “Your kidneys are smart; they’ll tell you when they need water.”
- A flu shot can give you the flu
Influenza kills roughly 36,000 Americans every year, but more than half of us routinely skip the yearly shot, with many believing it can give you the flu. That simply isn’t the case.
“The flu vaccine used today is made from proteins in the lab and doesn’t have live virus in it,” said OMRF immunologist Eliza Chakravarty, M.D. “So it can’t give you the flu.”
- Limit your intake of eggs
The idea that eggs and other high-cholesterol foods are dangerous is a long-held belief. But, said Prescott, “Unless you’re in the small minority of people who are hyper-sensitive to dietary cholesterol, there’s no evidence that eating high-cholesterol foods increases a person’s risk of heart disease.”
A recent analysis of data gathered from a study of 9,000 people found that reducing cholesterol in the diet actually correlated with increased mortality levels. “Eggs are a great source of protein, so if you like them, there’s really no reason to limit your intake.”
- Shaved hair grows back thicker, darker and faster
Your hair doesn’t grow back any differently because you shave it. The most common reason for this belief, said Prescott, “is that the act of cutting the hair gives it the illusion of being thicker and darker.”
When the razor cuts away the tip, it leaves the remaining hair blunt on the end. This may temporarily give the appearance of thicker, coarser hair, but it doesn’t actually change the circumference or color of hair follicles, nor does it change your hair’s growth rate.
- Cracking your knuckles causes arthritis.
“I used to get in trouble for this one a lot as a kid,” said Prescott. “Where this myth came from, I have no idea. But there is no evidence to support it.”
Prescott said the dramatic, loud noise of knuckles cracking might have been perceived as destructive, but it really isn’t. The “pop” occurs when bubbles burst inside the fluid inside that lubricates the joint.
Arthritis occurs in only one of two ways: either through autoimmunity where the immune system attacks your own joint, as in rheumatoid arthritis, or in the more chronic, degenerative osteoarthritis, which is caused by inflammation related to other factors like obesity. Still, Prescott said. “Even if I had proven that to my mom, she probably would have said, ‘Stop it anyway. It’s impolite.’”
OMRF announces 2017 Fleming Scholar class
OMRF has selected 13 Oklahoma high school and college students as Sir Alexander Fleming Scholars for 2017.
The students for OMRF’s 62nd class of Fleming Scholars were selected following a competitive statewide application and interview process. Those selected as scholars will spend eight weeks working side-by-side with OMRF scientists on specific research projects covering subjects such as autoimmune disease, cancer and cardiovascular disease.
At the program’s conclusion, the scholars will author scientific papers and deliver presentations to OMRF’s scientific staff.
“This unique program brings a sense of excitement to our labs every summer, reinvigorating our staff while also providing a once-in-a-lifetime opportunity for these bright students to get hands-on experience in a lab setting,” said OMRF Fleming Scholar Program coordinator Heather Hebert. “The experience allows students to see if a career in science or medicine is in their future, while also providing them with invaluable skills they can use in any career path.”
Since it launched in 1956, the Fleming Scholar Program has provided nearly 600 Oklahoma students with a first-hand look at careers in research and medicine. The program is named in honor of famed British scientist Sir Alexander Fleming, who discovered penicillin and came to Oklahoma City in 1949 to dedicate OMRF’s first building.
Two OMRF senior scientists, Judith James, M.D., Ph.D., and Rodger McEver, M.D., started their research careers as Fleming Scholars. James is the Program Chair OMRF’s Arthritis & Clinical Immunology Program, the foundation’s largest program, and McEver is the foundation’s Vice President of Research.
The 2017 Fleming Scholars, their hometowns and current schools, are:
Abigail Ballard, Norman, Austin College
Monica Davis, Jones, Northern Oklahoma College
Madeline Gish, Edmond, Hillsdale College
Kari Hall, Edmond, University of Oklahoma
Keirah Jefferson, Moore, Oklahoma School of Science and Mathematics
Kristy Johnson, Blanchard, Oklahoma State University
Jarett Lewis, Edmond, Bishop McGuiness High School
James Li, Edmond, Washington University in St. Louis
Han Li, Oklahoma City, Westmoore High School
Joshua Ross, Pryor, Oklahoma State University
William Towler, Edmond, Oklahoma State University
Henry Unterschuetz, Tulsa, University of Oklahoma
Kobby Wiafe, Bethany, Baylor University
For more information on the Fleming Scholar Program, visit www.omrf.org/fleming.
OMRF receives grant to study triggers of cancer, birth defects
OMRF has received a five-year, $1.7 million grant to look at how DNA replicates itself. The results could lead to new information about how cancer and birth defects develop.
The grant, awarded by the National Institute of General Medical Sciences, will allow OMRF researcher Chris Sansam, Ph.D., to better understand what goes wrong in cells during the development of cancer and birth defects by applying what is learned in a normal setting in the genes.
DNA replication is the process by which genes duplicate. Every human begins as one cell, but the body is comprised of billions, meaning countless cell divisions occur during a lifetime.
“Every time a cell divides, the entire genome has to be replicated accurately, but the mechanisms responsible for that are still largely unknown,” said Sansam. “If we can understand how things are supposed to operate under normal circumstances, then we can identify what happens when things go wrong.”
DNA replication occurs constantly in the body, said Sansam, starting from a single cell that contains all the genetic material inherited from each parent. As cells divide, a full complement of genetic material has to be copied and put into each new cell produced, so it is not surprising that things can go awry if mistakes occur in the process.
“If the genetic material isn’t copied accurately, that leads to cancer. If it happens during embryonic development, it causes birth defects,” said Sansam, who is an assistant member in OMRF’s Cell Cycle & Cancer Biology Research Program.
Sansam’s grant aims to understand exactly how this process functions by identifying the genes, molecules and mechanisms that are needed to correctly replicate our DNA.
To accomplish this, Sansam uses zebrafish, semi-transparent, aquatic creatures that grow to no more than an inch in length. The tiny fish, which are common in home aquariums, are especially good scientific subjects because they share 70 percent of humans’ genetic code.
“The zebrafish is an incredible model to study, because virtually all basic cellular processes are the same in fish as they are in humans,” said Sansam. “We can learn a lot about how things work in humans by first studying an accessible, low-cost organism like zebrafish.”
Sansam joined OMRF in 2010 from the Massachusetts Institute of Technology (MIT) in Cambridge, Mass.
“It is unusual for a young investigator to be successful in a first try at getting a grant of this magnitude funded,” said Gary Gorbsky, Ph.D., who heads the Cell Cycle & Cancer Biology Research Program at OMRF. “However, the research that Dr. Sansam proposed has so much novelty and importance that the grant review panel found it very exciting. We’re proud of the work that Dr. Sansam and his laboratory members are doing, and we anticipate many fantastic discoveries in the future.”
The grant, number 1R01 GM121703-01, is from the NIGMS, part of the National Institutes of Health.
Think you’re Irish? Your genes may say otherwise
When Saint Patrick’s Day rolls around, we all claim to be a little Irish. But this year, should we claim to be a little bit Russian, too?
A recent genetic study concluded that a good deal of the Irish population may actually have descended from ancient Russian migrants.
The research, published in 2016 in the Proceedings of the National Academies of Science, looked at DNA from the remains of three Irishmen who lived more than 4,000 years ago. The analysis showed that the trio shared a number of genetic traits with modern-day Irish. But it also showed that they bore a considerable genetic resemblance to people who lived long ago in the Russian steppes.
Oklahoma Medical Research Foundation geneticist Patrick Gaffney, M.D., an Irish American himself, said these findings are less surprising than they might at first seem. “Humanity has migrated all across the globe,” he said.
But just because Irish ancestry can trace back to Russian descent doesn’t mean the Irish don’t have their own unique genetic marks.
“When a population settles in one area and flourishes, migration can slow down and the population can be more isolated. That’s when mutation and evolutionary genetics sort of puts its own geographic fingerprint on the genome of those people,” said Gaffney.
This isolation of the Irish population on an island, said Gaffney, resulted in the increased sharing of certain genetic traits that became more prevalent, such as freckles and red hair.
So it’s not as simple as saying that the Irish are just transplanted Russians. The Irish are their own unique population, he said.
“If I went to Ancestry.com and had my DNA tested, my genetic results would show that I descended from ancestors in Ireland, but that’s not 100 percent of my genetic information,” said Gaffney. “There will also be traces of other regions from the world that could be seen.”
Irish is the second-most prominent ancestry in the United States—behind German—with 34.5 million people identifying their heritage as at least partly Irish. Gaffney said the Irish have been around long enough to evolve their own geographic genetic footprint that is different from their Russian ancestors.
So what does it mean to be Irish?
“I think for most people, it derives more from cultural perspective and family history than actual genetics,” said Gaffney. “It’s sort of a historical identity, where you can trace the family name to people across the ocean and have a definable lineage to those people. It’s a snapshot of your own personal history.”
And that’s a personal history Gaffney and his family celebrate, and not just on Saint Patrick’s Day. Gaffney’s children have learned Irish dance, and he plays a traditional Irish drum called a bodhrán. His wife plays an Irish tin whistle and flute. “We do some traditional Irish music now and again,” he said. “Whenever we feel the urge.”
Gaffney, for one, welcomes all to claim Hibernian ancestry on March 17.
“If you’re feeling a little Irish on Saint Patrick’s Day, that’s great,” he said. “We won’t bother to check your genetics.”
OMRF hosts junior scientists
The lab coats were baggy. The gloves ill-fitting. The safety glasses a touch loose. But if one thing fit just right for 17 elementary school students on Tuesday at OMRF, it was curiosity.
On Tuesday, OMRF hosted these budding scientists to give them a taste of real hands-on research at its annual Putnam City Junior Scientist Days.
For the past 39 years, OMRF has provided students from the PC school district with a unique opportunity to learn about science in a real laboratory setting, using high-powered microscopes and other state-of-the-art equipment.
Whether they’re learning to pipette, observing blood vessels, or watching tiny worms squirm under a microscope or learning about how DNA is analyzed, it’s an invaluable learning experience for students.
Tulakes Elementary student Aaren Underwood couldn’t stop smiling while extracting DNA from a banana. “I didn’t know bananas had DNA,” he said, still squishing the banana inside the bag. “I might want to be a scientist. It’s really fun!”
Xander Stone from Wiley Post Elementary also got to work with DNA and loved the experience. “It was so awesome getting to see DNA and cells up close; it’s different to see it for yourself than to learn about it,” he said, grinning from ear-to-ear. “It’s a lot of fun and really cool.”
Few traditions generate the buzz around OMRF quite like Junior Scientist Days, stoking the fire of young minds and reenergizing the scientists who do research every day.
“This event means a ton to OMRF, and we see the benefit of it in the bright eyes and smiles of the children in the labs,” said OMRF director of development Allison Parker. “OMRF is so appreciative of everything Putnam City has done for us and we love being able to give back in this way. Seeing the students so excited is very special and something we always look forward to.”
Parents and school officials in attendance were treated to a presentation by cancer researcher Linda Thompson, Ph.D., followed by a tour of the foundation’s facilities.
Thompson holds the Putnam City Schools Distinguished Chair in Cancer Research at OMRF, which was established by the PC Cancer Drive. The funding has helped support numerous projects, including research from Thompson’s lab leading to the world’s first genetics-based risk assessment test for breast cancer.
“This is always a special day at OMRF and it’s an opportunity for us to give back to the students of this district who have done so much for us,” said Thompson. “We are incredibly fortunate to have such a devoted partner in the fight against cancer, and these energetic young scientists are proof that the future is bright.”
This year’s event was sponsored by Cox Communications.
“As a technology company, Cox understands the critical importance of exposing students to STEM activities early. At OMRF, we have some of the top scientists and researchers in the world, right here in Oklahoma City,” said Cox Business Sales Director Ashley Perkins. “The decision to support a program that gives Putnam City students the opportunity to work side by side with these scientists was an easy decision for our company. The students participating in Junior Scientist Day represent the future leaders of our businesses and communities, and Cox is proud to play a part in helping to develop those leaders.”
After more than 41 years of continued support, the PC school district has raised more than $3.4 million for the Oklahoma City-based nonprofit institute’s cancer research programs. OMRF hosted elementary students from PC schools on Tuesday and the middle school and high school students on Friday. The students are hand-selected by teachers.
“One of the things I love about Junior Scientist Day is seeing the engagement in learning by students,” said Putnam City superintendent Dr. Fred Rhodes. “You can see it in their faces as they work in labs and you hear it when you talk to them when the day is over that they have experienced something that means a great deal to them. It’s clearly a very special opportunity for hands-on, active learning.”
Investigating the role of obesity in arthritis
Research from OMRF has revealed new findings on the effects of obesity and on fat tissue in the knee joint in the formation of osteoarthritis, the most common form of arthritis.
Osteoarthritis, or OA, is the most common form of disability in the U.S., affecting nearly 27 million Americans. It occurs when the cartilage that cushions bones in the joints breaks down and wears away, leaving the bones to painfully rub against one another. This is most commonly found in the knees, hips, fingers, lower back and neck.
To better understand disease onset, OMRF researchers Tim Griffin, Ph.D., and Erika Barboza Prado Lopes, Ph.D., looked at fat tissue in the knee joint known as the infrapatellar fat pad. Their research centered on whether a high-fat diet causes the fat pad in the knee to become inflamed, which then contributes to the formation of OA.
“Obesity, particularly from excess abdominal fat, causes a low level of inflammation throughout the body that is thought to increase the risk of osteoarthritis in the knee,” said Griffin. “We used that knowledge to ask a more specific question: Is the knee fat pad itself also a source of inflammation with obesity that is part of this increased risk of osteoarthritis?”
In order to find the answer, the scientists took a step back in the research process. Griffin said they already knew they could feed mice a high-fat diet and cause OA of the knee. But they needed to study what happened in the fat pad under the conditions of a high-fat diet before OA develops to know if it could be causing the disease. This study, Griffin said, was one of the first of its kind to look at the fat pad in a pre-disease stage.
“We started far enough into the diet where we could see inflammation in the abdominal fat, but not so far that the cartilage became damaged in the knee,” said Griffin. “This let us look at the early changes happening in the joint but not at the stage where there is full-on osteoarthritis.”
The researchers made an unexpected discovery: Obesity increased the size of the knee fat pad without causing it to become inflamed.
Because the fat pad in the knee did not become inflamed with the high-fat diet, the researchers do not believe it is initiating the increased risk of OA. But it may still play a role in overall joint health, said Lopes.
According to Lopes, studies like this may ultimately hold the key to developing new therapies for osteoarthritis. “We have to understand the basic mechanisms at work and ask questions about how each tissue in the joint contributes to the overall health of the joint. Perhaps the increase in fat pad size without the inflammation is a protective response. This answer isn’t what we anticipated, but it helps push us in the right direction.”
The new findings have been published in the journal Arthritis & Rheumatology.
OMRF researchers Florea Lupu, Ph.D., Susan Kovats, Ph.D., and Rheal Towner, Ph.D., also contributed to the research, which was supported by grants from the National Institutes of Health (numbers P20-RR-018758, P20-GM-103441 and R03-AR-066828) and the Arthritis Foundation.
Researchers make new insights into birth defects, infertility
A team of researchers has discovered a critical process responsible for producing the correct number of chromosomes in healthy offspring.
The research, published in the journal Science, shows that genetic events during the division of reproductive cells are regulated by a system that marks proteins to be destroyed. When the timing of this destruction goes wrong, it results in the incorrect number of chromosomes in either the sperm in the male or the egg in the female, which can cause birth defects.
OMRF scientist Roberto Pezza, Ph.D., who contributed to the new study, explained that the process by which these proteins are targeted for destruction has been known to affect other processes. “But it had never been shown before in the context of reproductive cells in mammals,” he said.
This process occurs during meiosis, a specific type of cell division that produces the sperm and egg. When these join to create offspring, the correct number of chromosomes must be present in each. But if this fails to happen, said Pezza, “It can create significant negative effects on human health and development.”
Abnormal numbers of chromosomes—known as aneuploidy—are a common cause of genetic disorders and birth defects, including Down syndrome, Turner syndrome, Klinefelter syndrome and spontaneous abortion.
The research shows that cells that undergo meiosis also experience being marked for destruction.
“Marking proteins for destruction is not a bad thing. It is as important to the cycle as their creation, but the timing of it is critical,” said Pezza.
Pezza joined OMRF in 2008 from the National Institutes of Health in Bethesda, Maryland, where he was a research fellow. In his lab at OMRF, he studies how the chromosomes segregate during cell division and what causes errors in the process, which are the leading causes of birth defects.
This new information, he said, may help scientists more firmly grasp the basic processes that facilitate proper chromosome segregation and the production of healthy reproductive cells.
“By knowing these processes, now we have the potential to predict, treat and possibly even prevent these aneuploidy-based human diseases in the future,” Pezza said.
Pezza collaborated with researchers at the University of California, Davis, on the work. His research was supported by grant number GM103636 from the National Institute of General Medical Sciences and March of Dimes grant 1-FY14-256.
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