For some, a summer internship is merely a stepping stone into their career. But for Brendan Creemer, a junior biology major at Portland’s Lewis & Clark College, a recent summer internship meant so much more.

Creemer has Usher syndrome, a genetic disorder that causes progressive vision loss and deafness. He spent much of the summer in the laboratory of the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) with neuroscientists Martha Neuringer, PhD and Trevor McGill, PhD, working on a method to improve the ability to use stem cells as a possible treatment for the disorder.

For more than 40 years, Neuringer has taken on high school and college summer interns, but Creemer is the first intern to live with the often-debilitating symptoms of Usher syndrome.

“I’ve been working for many years on retinal diseases and potential therapies without that personal connection,” said Neuringer, a professor in the Division of Neuroscience at the ONPRC and research associate professor of ophthalmology in the OHSU School of Medicine. “It’s all the more motivation when you know what it’s like for someone facing this.”

Creemer sought out the internship after learning about the research through the OHSU Casey Eye Institute.

“You have that choice to either give up and assume everything is hopeless or choose to take action and not only help yourself but others around you as well,” he wrote of his experience.

Creemer’s summer project focused on a key issue for stem cell therapies: rejection of transplanted cells. When stem cells are delivered as therapies for any health issue, they are perceived as “non-self” by the recipient and attacked by the immune system. Creemer analyzed a possible method to suppress the immune system in rodents, which was then tested to see if it enhanced the survival of retinal stem cell transplants.

“It makes it so much more palpable and real when you see how someone deals with their limitation and overcomes it,” Neuringer said. “It was a perfect match.”

The scientists at the NPRCs across the country are focused on solving myriad genetic disorders. Discover more of our latest research here.

Children born to HIV-positive mothers are susceptible to contracting the disease themselves, but scientists at Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) have new evidence suggesting that newborn infection may be entirely preventable.

The researchers successfully demonstrated, in a non-human primate model, that a single dose of an antibody-based treatment given after virus exposure can prevent HIV transmission from mother to baby, provided that dose is given at the correct time. 

The study found that rhesus macaque newborns did not develop the monkey form of HIV (known as SHIV), when they received a combination of two antibodies 30 hours after being exposed to the virus. This is the first time a single dose of broadly neutralizing antibodies given after viral exposure has been found to prevent SHIV infection in nonhuman primate newborns.

However, when the antibody treatment was delayed until 48 hours after exposure, half of the baby macaques developed SHIV, even when given four smaller doses of the same antibody. 

Previous research by this group has shown that four doses of antibodies started 24 hours after exposure also prevented SHIV infection, and the current ONPRC study suggests that a three-week course of antiretroviral therapy given after virus exposure could also prevent HIV transmission to newborns.

“These promising findings could mean babies born to HIV-positive mothers can still beat HIV with less treatment,” said Nancy Haigwood, PhD, ONPRC director and a professor of pathobiology and immunology at the OHSU School of Medicine.

Antibodies aren’t toxic and can be modified to last a long time in the body, which reduces treatment frequency. This means antibody treatments may also help prevent negative side effects from the drug combination currently given to infants born to HIV-positive mothers.

Next, ONPRC scientists plan to see if different antibodies, or a combination of antibodies and antiretroviral therapy, could be even more effective. They also hope to find out whether the antibodies actually eliminate HIV or only prevent it from replicating.combination. This suggests that there is a 30-hour limit for the successful use of antibodies to prevent HIV transmission to newborns.

Scientists have made one more step toward the treatment and cure of multiple sclerosis (MS) by developing a compound that successfully promotes the regeneration of the protective myelin sheath around nerve cells.

In a recent study, scientists at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) described successfully testing the compound in mice, and they have already started to apply it to a rare population of macaque monkeys who develop a disease that is similar to MS in humans.

“I think we’ll know in about a year if this is the exact right drug to try in human clinical trials,” said senior author Larry Sherman, PhD, an OHSU professor in the Division of Neuroscience at the primate center. “If it’s not, we know from the mouse studies that this approach can work. The question is, can this drug be adapted to bigger human brains?” 

The discovery arrives after more than a decade of research following a 2005 breakthrough by Sherman’s lab. In that study, scientists discovered that a molecule called hyaluronic acid (HA), accumulates in the brains of patients with MS. The researchers then linked this accumulation of HA to the failure of cells called oligodendrocytes (which generate myelin) to mature. 

Myelin forms a protective sheath covering each nerve cell’s axon—the threadlike portion of a cell that transmits electrical signals between cells. Damage to myelin is associated with MS, stroke, brain injuries and certain forms of dementia like Alzheimer’s disease. Delay in myelination can also affect infants born prematurely, leading to brain damage or cerebral palsy. 

Other studies led by the Sherman lab have shown that HA is broken down into small fragments in multiple sclerosis lesions by enzymes called hyaluronidases, and these fragments send a signal to immature oligodendrocytes to not turn on their myelin genes. 

There is currently no cure for MS, but an international team of researchers led by OHSU has been working to develop a compound that neutralizes the hyaluronidase in the brains of patients with MS and other neurodegenerative diseases. This will ideally revive the ability of progenitor cells (descendants of stem cells that differentiate, or change, into specific cell types) to mature into myelin-producing oligodendrocytes and regenerate myelin sheath. 

The ONPRC macaque study describes a modified flavonoid—a class of chemicals found in fruits and vegetables—that does just that. The compound, called S3, reverses the effect of HA and promotes functional remyelination in mice. 

“It’s not only showing that the myelin is coming back, but it’s causing the axons to fire at a much higher speed,” Sherman said. “That’s exactly what you want functionally.”

The next phase of research involves testing, and possibly refining, the compound in macaque monkeys who carry a naturally occurring version of MS called Japanese macaque encephalomyelitis. The condition, which causes clinical symptoms similar to multiple sclerosis in people, is the only spontaneously occurring MS-like disease in nonhuman primates in the world. 

Researchers at the ONPRC and other NPRC locations are consistently making breakthrough discoveries to help treat and eradicate MS and other neurological diseases. Learn more about the latest findings here.

In the midst of the novel coronavirus (COVID-19) outbreak, scientists at the National Primate Research Centers (NPRCs) have initiated research programs to better understand and diagnose as well as develop potential treatments and vaccines for the disease. NPRC animal colonies will be key in moving SARS-CoV-2 infection/COVID-19 research from cell models to studies in whole living systems so researchers can determine treatment safety and effectiveness.

Since the virus began to spread at the end of 2019, more than 3 million people have been infected worldwide as of April 28, 2020, with numbers growing daily. The coordinated efforts of the scientific community will be crucial to slow the spread of COVID-19, lower the risk of transmission and treat those who have the disease.

NPRC COVID-19 Research

Several of the NPRCs have made public announcements that research is under way, including California NPRC, Southwest NPRC, Tulane NPRC and Wisconsin NPRC. Others, including Oregon, Washington and Yerkes NPRCs, are also beginning research, and Oregon and Yerkes are accepting applications for COVID-19 pilot projects, which facilitate research collaborations and provide important preliminary data.

California NPRC researchers have already isolated, characterized and cultured COVID-19 from a patient treated at UC Davis, the first community-acquired case in the U.S. Next, they plan to make diagnostic tests in-house.

The Southwest NPRC scientists are proposing research projects to establish a nonhuman primate model to study the development and transmission of the disease, test new detection methods and partner with others in the scientific community.

At Tulane NPRC, researchers plan to create a nonhuman primate model to study the disease’s clinical progression, how it is transmitted through the air and how it specifically affects aging populations. The scientists are aiming to answer many questions, including why older individuals are more susceptible to complications and death from COVID-19.

In Wisconsin NPRC researchers have developed a coalition of scientists to combat the disease, drawing heavily from their firsthand experience during the Zika virus outbreak in 2016.

Yerkes NPRC researchers have begun initial research, and the center’s goals include understanding immunity and antibody response to SARS-CoV-2, and developing diagnostics, key reagents, antiviral therapies and vaccines.

COVID-19 Research Safety

The NPRCs are well-positioned to conduct SARS-CoV-2 infection/COVID-19 research because of our expertise in infectious diseases and collaborations internally at each NPRC as well as across NPRCs and with colleagues worldwide. Also, we can conduct such research safely in our Biosafety Level 3 (BSL3) facilities specifically designed to keep personnel, the research and the environment safe. Examples of BSL3 safety features include additional training and oversight for employees, directional air flow and filtered ventilation systems, and specialty equipment to contain the virus isolates used in the research and to decontaminate the lab space and research equipment and supplies.

News Stories about NPRC COVID-19 Research

Recent news articles by STAT News, Bloomberg, The Scientist and ABC News provide more information about the NPRC studies and the critical role of research with animals.

As we have more information to share about NPRC COVID-19 research, we’ll post information at NPRC.org/news and tweet from @NPRCnews. In the meantime, here are a few helpful COVID-19 resources we’re following.

At the NPRCs, our focus is conducting research and caring for our irreplaceable animal colonies so we can help people and animals live healthier lives. In the midst of the global COVID-19 pandemic, we are prioritizing our research to focus on developing diagnostics, preventions and treatments for this novel disease.

As we work to combat this health crisis, we also want to help keep you informed about the latest developments. Below are some of the resources we are following. These organizations are on the front lines of combatting COVID-19 and are frequently sharing crucial information regarding public health, personal guidelines and coronavirus research.

Centers for Disease Control and Prevention (CDC)
https://www.cdc.gov/coronavirus/2019-ncov/index.html
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html

World Health Organization
www.who.int/emergencies/diseases/novel-coronavirus-2019

National Institutes of Health
https://www.nih.gov/health-information/coronavirus

In addition, we want to provide resources to help address any mental health and emotional well-being concerns COVID-19 brings for you and your loved ones:

CDC’s Recommendations for Managing Anxiety and Stress
https://www.cdc.gov/coronavirus/2019-ncov/prepare/managing-stress-anxiety.html

National Alliance on Mental Illness
https://www.nami.org/About-NAMI/NAMI-News/2020/NAMI-Updates-on-the-Coronavirus

Just for Kids: A Comic Exploring the New Coronavirus
https://www.npr.org/sections/goatsandsoda/2020/02/28/809580453/just-for-kids-a-comic-exploring-the-new-coronavirus

The NPRCs are working closely with our collaborators worldwide to address COVID-19. Look for updates from us at NPRC.org and @NPRCnews.

Thanks to recent research conducted by scientists at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU), a new avenue to in vitro fertilization (IVF) could soon be opened for prospective parents who were previously told it was unadvisable or impossible.

A perfect embryo contains 46 perfect chromosomes, but some have more, and others have fewer. The result is a common abnormality known as aneuploidy, which occurs in as many as 80 percent of human embryos. Because aneuploidy has been linked to a risk of in vitro fertilization failure, miscarriage and certain genetic orders or birth defects, mosaic embryos— those with both normal and abnormal cells—have not been considered ideal candidates for IVF transfer.

For prospective mothers who only produce mosaic embryos, this can mean the IVF journey may end before it begins. But that could change very soon.

The ONPRC study, led by Shawn L. Chavez, PhD, an assistant professor of reproductive and developmental sciences at ONPRC at OHSU, and an assistant professor of obstetrics and gynecology, and physiology and pharmacology in the OHSU School of Medicine, is the first to confirm mosaic embryos can adapt and persist in development in a nonhuman primate model, resulting in positive IVF outcomes.

Using advanced time-lapse imaging and single-cell sequencing techniques to precisely track the development of mosaic embryos of a rhesus macaque, Chavez and team identified a relationship between mosaicism and two other biological processes: cell fragmentation and blastomere exclusion.

In utero and after IVF, large cells formed by the division of a fertilized egg, known as blastomeres, may break down into small pieces called cellular fragments. These fragments, it seems, can serve as a sort of cellular cleanup crew.

“We found that both the blastomeres and their fragments can act as trash bins within the embryo. As DNA-carrying cells divide and/or fragment, the embryo appears to naturally identify which blastomeres have genetic abnormalities and stop them from further development,” said Chavez.

He further explained that by the stage in which an embryo would implant into the uterus, these abnormal cells or DNA have been visibly excluded from the rest of the embryo, suggesting that imperfect IVF embryos could be considered for use in transfer and could possibly endure in utero.

According to Paula Amato, MD, an associate professor of obstetrics and gynecology in the OHSU School of Medicine, this discovery could positively impact IVF processes for humans in the future.

 “While selecting embryos with a normal chromosome complement is preferred and carries a high chance of pregnancy success, it is not a guarantee,” she explained. “For patients with only mosaic embryos available for transfer, these findings suggest that in some cases, these embryos will result in apparently normal pregnancies.”

Ongoing research will use live-cell time-lapse imaging to better understand the relationship between aneuploidy, cell fragmentation and blastomere exclusion within the embryo. The scientists believe these results could open up new avenues for testing mosaic human embryos.

“We expect that the overall results will be similar to the story of the ‘dark horse,’” said Chavez. “While not perceived as a contender at the start of the IVF race, a mosaic embryo may still be capable of winning and resulting in something wonderful.”

Medications like chemotherapy and radiation are highly effective in treating cancer and benign tumors, but these therapies can also increase the risk of infertility. One in three childhood cancer survivors carry this risk, and for those undergoing treatment prior to puberty, common fertility preservation processes for adults—such as sperm or egg freezing—are not an option. 

But there may be newfound hope.

Recent research from the University of Pittsburgh School of Medicine, Magee-Women’s Research Institute and Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University has found immature testicular tissue can be cryopreserved, or frozen, and later used to restore fertility.

Using a nonhuman primate model of cancer survivorship, the researchers removed one testis each from prepubertal rhesus macaques and cryopreserved the immature testicular tissue. Later, the researchers thawed and transplanted pieces of the tissue under the skin of the same animal.

Approximately one year later, the testicular skin grafts were removed and compared to samples of the immature tissues. Not only were the grafts able to produce enough testosterone for the animal to undergo puberty, but they were also found to contain an abundance of mature sperm.

Scientists at ONPRC then used the samples to generate viable embryos through intracytoplasmic sperm injection, or ICSI, where individual sperm were recovered from the graft tissues and injected directly into an egg. The embryos were successfully transferred to recipient females, and in April 2018, a healthy female baby named “Grady” was born.

“The ability and choice to have a family should not be determined by the risks of necessary medical treatment,” said Carrie Hanna, PhD, director of the Assisted Reproductive Technology Core at ONPRC. “Grady represents an important step toward ensuring that children maintain their opportunity to have a family later in life, should they choose to do so.”

Frequent alcohol use among adolescents and young adults has the potential to be dangerous for obvious reasons—and now, new research in nonhuman primates shows it can actually slow the rate of growth in developing brains.

Researchers at Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) in Portland, Oregon, measured the brain growth of 71 rhesus macaques via magnetic resonance imaging (MRI). The macaques voluntarily consumed ethanol or beverage alcohol, and the scientists measured their intake, diet, daily schedules and health care, ruling out other factors which tend to confound results in observational studies involving humans.

The study shows heavy alcohol use reduced the rate of brain growth by 0.25 milliliters per year for every gram of alcohol consumed per kilogram of body weight, in addition to reduced growth of cerebral white matter and the subcortical thalamus. These findings help validate previous research examining the effect of alcohol use on brain development in humans.

“Human studies are based on self-reporting of underage drinkers,” said co-author Christopher Kroenke, PhD, an associate professor in the Division of Neuroscience at ONPRC. “Our measures pinpoint alcohol drinking with the impaired brain growth.”

The study is the first to identify normal brain growth in rhesus macaques in late adolescence and early adulthood as occurring at a rate of 1 milliliter per 1.87 years. It also supports previous studies which show a decrease in the volume of distinct brain areas due to voluntary consumption of ethanol.

Lead author Tatiana Shnitko, PhD, a research assistant professor in the Division of Neuroscience at ONPRC, said previous research has shown the brain has a capacity to recover at least in part following the cessation of alcohol intake. However, it’s not clear whether there would be long-term effects on mental functions as the adolescent and young adult brain ends its growth phase. The next stage of research will explore this question.

“This is the age range when the brain is being fine-tuned to fit adult responsibilities,” Shnitko explained. “The question is, does alcohol exposure during this age range alter the lifetime learning ability of individuals?”

Alcoholism isn’t easily explained, but it can have devastating effects for sufferers and their friends and families.

New research conducted at Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University has identified a gene which could be a new target for developing medication to prevent and treat this psychological disease.

In the study, researchers modified the levels of a protein in mice which is encoded by a single gene, GPR39—a zinc-binding receptor previously associated with depression. The prevalence rates of co-occurring mood and alcohol use disorders are high, and people with alcohol use disorder are 3.7 times more likely to have major depression than those who do not abuse alcohol.

Using a commercially available substance which mimics the activity of the GPR39 protein, the researchers found targeting this gene dramatically reduced alcohol consumption in the mice. The team also discovered a link between alcohol and how it modulates the levels of activity of this particular gene. Researchers found when they increased the levels of GPR39 protein in mice, alcohol consumption dropped by almost 50 percent without affecting the total amount of fluid consumed or overall well-being of the mice. 

 “The study highlights the importance of using cross-species approaches to identify and test relevant drugs for the treatment of alcohol use disorder,” said senior author Rita Cervera-Juanes, PhD, a research assistant professor in the divisions of Neuroscience and Genetics at ONPRC.

To determine whether the same mechanism affects people, the researchers are now examining postmortem tissue samples from the brains of people who suffered from alcoholism.

By testing the effect of this substance in reducing ethanol consumption in mice—in addition to its previously reported link in reducing depression-like symptoms—the findings may point the way toward developing a drug which both prevents and treats chronic alcoholism and mood disorders in people.

“We are finding novel targets for which there are drugs already available, and they can be repurposed to treat other ailments,” Cervera-Juanes said. “For alcoholism, this is huge because there are currently only a handful of FDA-approved drugs.”

Over the past 150 years, the average onset of puberty has been steadily declining. A century and a half ago, girls reached reproductive competence around 17.5 years of age—but now, the average age is 12.5 years. Early-onset puberty can lead girls to experience health problems later, including increased incidence of ovarian, uterine and breast cancers, as well as being at a higher risk for cardiovascular and metabolic diseases.

Researchers at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) and the Brigham & Women’s Hospital and Harvard Medical School, wondered what was causing this increase in early bloomers. Their research led to the discovery of a new gene (MKRN3) that serves as a “neurobiological brake”, that when mutated advances pubertal development. Children with mutations in the MKRN3 gene show signs of pubertal development as early as 5 years of age. Without this biological pause button, developing kids would be more susceptible to cancer, cardiovascular disease, and metabolic disorders.

“Developing our knowledge of how genes regulate the initiation of puberty will allow us understand why girls are initiating puberty at much earlier ages,” said Dr. Alejandro Lomniczi, lead researcher on the study and assistant professor for the Division of Neuroscience at the ONPRC.

Focusing on the hypothalamus, the ventral part of the brain that controls reproductive development, Lomniczi and colleagues demonstrated that in monkeys and rodents, the MKRN3 gene is highly expressed during infancy and gets shut down right before puberty. Using genetic and biochemical approaches they demonstrated that MKRN3 is a strong repressor of KISS1 and TAC3 gene expression, two strong activators of pubertal development.

With these discoveries guiding their work, researchers are starting to construct the genetic architecture that regulates reproductive development in the brain and one step closer of breaking the “puberty” code.

Updated: June 2020