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.

We can’t stop aging—but can we slow down its consequences?

Scientists at the Southwest National Primate Research Center (SNPRC) on the Texas Biomedical Research Institute campus are working to find an answer using an animal model that continues to prove effective in this area.

Associate Professor Corinna Ross, PhD, and Professor Suzette Tardif, PhD, along with a team of researchers, conducted a study on adult marmosets (ages 2-17) that had been transferred to SNPRC from the New England Primate Center in 2015. Marmosets, in general, are recognized as an ideal nonhuman primate model of aging because they have relatively short lifespans and share age-related diseases similar to those of people.

Scientists took blood samples from the animals before and after the move, then re-evaluated them two years later. The team found that low levels of tryptophan metabolism were found to be associated with an increased risk of death.

Tryptophan is an amino acid that is linked to the production of serotonin, the chemical in the brain that contributes to feelings of happiness. Scientists aren’t yet sure whether serotonin influences aging, but there is a link between levels of tryptophan and health, Ross indicated.

The study also found that the metabolism of two other amino acids, betaine and methionine, were associated with aging regardless of environmental factors like stress. The results of the study suggest that the levels of metabolism of these three amino acids could be potential biomarkers for aging and related health issues.

This is “one of the first studies to discover metabo-lites (small molecules) [the levels of which] predict future mortality over a several year time span,” the authors concluded.

Following this study, marmosets may help scientists understand the subtleties of physiological aging and find ways to fight its negative health effects.

Curious about what other factors affect aging? NPRC research indicates the amount of calories you consume could have an impact as well.

The way that HIV—the virus that causes AIDS—spreads and progresses over time varies among people.

A recent study by scientists at Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute shows this variance may be at least partially explained by a genetic mechanism, a discovery that could open the door for more targeted treatments.

A team of scientists led by Assistant Professor Smita Kulkarni, PhD, and Mary Carrington, PhD, conducted the study, which revealed that a specific long “noncoding” RNA molecule influences a key receptor involved in HIV infection and progression. Dr. Kulkarni said that until the last decade or so, scientists thought many of these particular RNAs were “junk.” Thanks to recent developments in technology and genomics, however, the scientific community has been able to examine them further.

The team of researchers showed that the long non-coding RNA molecules impact the genes encoding an HIV co-receptor known as CCR5. Since CCR5 is critical for the HIV virus to enter the cell, its various expressions can affect the infection’s outcome. Genomic DNA from various groups, including Hispanics, African Americans and Japanese, showed that this is present across many ethnicities, which means it can likely be explained by a single functional mechanism.

“Finding functional mechanisms of the disease-associated gene regions will increase our understanding about how they regulate disease-associated genes and pathways,” Kulkarni explained. “We may be able to find selective targets for (HIV) therapy.”

Kulkarni further stated that these discoveries may have implications for the progression of other infectious diseases as well.

“There are many ways we can use the techniques we have learned through this study—what we have established in our lab,” she said. “We can apply it to many other pathogens currently being studied by scientists at Texas Biomed and at many other institutions.”

Understanding these mechanisms is just part of the equation in fighting HIV. See how other ongoing research at the NPRCs is helping purge HIV “reservoirs” from the body.

Do certain changes in genes influence a person’s propensity to develop obesity? That’s what researchers at Texas Biomedical Research Institute, home to the Southwest National Primate Research Center, are aiming to find out in a new study.

The Centers for Disease Control (CDC) calls U.S. obesity an “epidemic,” with 40% of adults and 19% of children considered obese. Within children, however, there are disparities among ethnicities. Hispanic children have the highest rate of obesity at 26% compared to African American (22%), Caucasian (14%) and Asian (11%) children.

The team will be studying an area of research called epigenetics—which describes changes to DNA, RNA or proteins that are affected by both the environment and genetic makeup.

“If we start at the cellular level and then look at whole organisms like the human body and how we use energy, then we can identify pathways that are involved in the development of obesity and also potentially mechanisms by which we can intervene and treat obesity,” explained Associate Scientist Melanie Carless, PhD.

The first phase of the study will involve a group of 900 Texas Hispanic children who have a high propensity for obesity. Scientists will examine whether physical data like caloric intake, physical activity, energy expenditure, metabolic rate and glucose levels are related to another factor called DNA methylation to increase risk for obesity. In the second phase, scientists will compare changes in blood with changes in muscle tissue and muscle cells and see how these changes correlate. The third phase will involve the use of CRISPR (a new technology used to alter DNA sequences and modify gene function) to change the methylation levels in cells and see how this impacts energy use.

The information gathered from the study could lead to more targeted drug therapies for obesity, or someday, editing to correct an underlying issue at the DNA level. This could improve public health in a number of ways.

“Obesity can be a huge factor in serious medical problems including diabetes, high blood pressure, atherosclerosis and heart disease,” said Carless. “We need to understand how obesity develops at a young age and the impact this might have on health later in life. If we can start to reduce the rates of obesity in the U.S., we will start to see a decline in multiple other disorders.”

We all know that proper diet and exercise are supposed to help us maintain a healthy weight. But in some cases, genetics may make it incredibly difficult to keep excess fat away.

Texas Biomed researcher Raul Bastarrachea, MD, and the team at Southwest National Primate Research Center (SNPRC) recently set out to discover why exactly some people are naturally inclined toward obesity. In the process, they found a mutation that affects leptin — a protein produced by fat cells that travels to the brain and signals to the body that there is enough fat and no more food is needed.

Simply put, leptin is a hunger suppressor.

In the study, Bastarrachea and team examined the case of two sisters in Colombia who started their lives as normal-weight babies but who quickly experienced childhood-onset severe obesity. Both were found to have a mutation in the leptin gene on chromosome 7, causing their leptin levels to be so low they were below the detection limit of the manufactured test kit.

The gene mutation forced the leptin proteins to be “misfolded,” rendering them ineffective and destroying their function.

When researching the genetics of the family, scientists noted these women were children of lineal consanguinity, which means several generations before them married blood relatives. This is a common practice in about a fifth of the world population, mostly in the Middle East, West Asia and North Africa, and increases health risks for children of these unions, including rare diseases caused by recessive genes.

Bastarrachea noted a greater understanding of this mutation and its causes is another step toward fighting global obesity.

“We keep learning more and more about the role of fat in normal-weight people,” he noted. “By researching what goes wrong when genes don’t code correctly for the production of leptin, we are coming closer to answers that could help millions of people with metabolic disorders.”

To help get those answers, the SNPRC is looking at obesity within its nonhuman primate (NHP) colony. 

“Fortunately, we have less than 5% obesity in our 2,500 NHPs and an even lower rate of diabetes at 1.5%, due to the low-carb Purina chow they eat and the activity they display given the comfortable size of their housing,” said Bastarrachea. 

Occasionally, a few of SNPRC’s baboons may experience excessive growth leading to excess body fat. 

“We speculate these animals may have particular gene mutations that mimic the extreme obese phenotype of the few individuals reported in scientific literature. We consider our baboon subgroup a valuable model of extreme obesity given NHPs share up to 98% genetic similarities with humans, thus allowing obesity study results in NHPs to be easily translated to humans,” Bastarrachea concluded. 

Ebola virus is a continuing threat in Central and West Africa, with an outbreak currently taking place in the Democratic Republic of Congo. But the factors that determine who is most susceptible to Ebola infection are still a mystery.

Now,  researchers at Texas Biomedical Research Institute, home to the Southwest National Primate Research Center —in collaboration with the University of Iowa—are investigating how malaria infections could impact people exposed to Ebola virus, since both diseases are common and recurring in the Congo.

Other co-infections are known to impact each other’s outcome. For example, patients infected with HIV-1, a virus that causes AIDS, are more susceptible to tuberculosis infection.

“A significant number of people entering Ebola Virus Treatment Units during the 2014-2016 West African outbreak were infected with both the malarial parasites, Plasmodium falciparum, and Ebola virus,” explained Professor Wendy Maury, PhD, the lead investigator at the University of Iowa.

The hypothesis is that people with an acute (active and recent) malarial infection, where the body’s immune response is already ramped up, have a greater chance of surviving Ebola infection. However, if people have chronic malaria, then they are hypothesized to be more susceptible to Ebola.

The researchers will begin by taking white blood cells from infected mice and studying them to determine what role they may play in dual malaria/Ebola infection. Knowing if the hypothesis is supported might change how doctors design therapies for Ebola in areas where both diseases are present, perhaps paving the way for more tailored therapeutics.

SNPRC’S part in the study will be a two-year process. The next step may involve testing in a higher-level animal model, such as nonhuman primates.

Photo credit: National Institute of Allergy and Infectious Diseases

Tuberculosis is a major concern for HIV/AIDS patients, as a full one-third of all patients with the autoimmune disease die of complications from TB.

But Professor Deepak Kaushal, PhD, of the Southwest National Primate Research Center (SWNPRC) at Texas Biomedical Research Institute, says recent research could help scientists better understand how to prevent this deadly condition.

It’s known the same mechanism of HIV/AIDS which leads to the loss of immune cells (CD4 and T cells) in other parts of the body also targets the lungs, allowing latent Mycobacterium tuberculosis (Mtb) bacteria infection to become active TB. But until now, scientists weren’t sure which parts of the lungs were targeted by the immunodeficiency.

Kaushal and a team of researchers conducted a study on rhesus monkeys infected with TB and SIV (simian immunodeficiency virus), using tissue either from a humanized mouse model or from humans. The findings indicated not all T cells in the lungs are affected by HIV—only the ones embedded inside the lung tissue. T cells in the lung sacs (alveoli) where oxygen enters the blood stream were still functional.

“If our findings are validated in future testing, this leads to the potential for new therapies that would prevent the loss of these crucial T cells during HIV infection,” Kaushal said. “The idea is that fewer HIV patients would progress to TB.”

Kaushal further explained, “[This is] important to know because we can target vaccines, therapeutics and drugs to these specific T cells in the lungs.”

According to a new study by scientists at the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute, marmosets can mimic the sleep disturbances, changes in circadian rhythm and cognitive impairment in people with Parkinson’s disease.

This is a significant development since an effective animal model that can emulate both the motor and non-motor symptoms of Parkinson’s gives scientists a better chance of understanding the processes responsible for changes in the brain caused by the disease.

Parkinson’s disease affects one million people in the United States and 10 million people worldwide. With the aging population, the incidence of the neurodegenerative disorder is on the rise. Each year, 60,000 people are diagnosed with Parkinson’s in the U.S. alone. The hallmark symptoms include tremors, slow movements, balance problems and rigid or stiff muscles. However, non-motor symptoms—including disorders of the sleep-wake cycle and problems thinking clearly—can be just as difficult for patients to handle.

During the study, the researchers tracked marmosets using devices around their necks similar to popular human fitness tracking devices. They wanted to see if the marmosets with induced classic Parkinson’s motor symptoms could also serve as an effective model for non-motor symptoms. In addition, scientists videotaped the animals to monitor their ability to perform certain tasks and how those abilities were impacted over time by the disease.

As it turned out, the marmosets did exhibit both motor and non-motor symptoms similar to those experienced by humans with the disease.

“Most of the early studies in Parkinson’s have been conducted with rodents,” explained lead author and Associate Scientist Marcel Daadi, PhD, leader of the Regenerative Medicine and Aging Unit at the SNPRC. “But there are some complex aspects of this disease you simply cannot investigate using rodents in a way that is relevant to human patients.”

“This study is a great first step,” Dr. Daadi continued. “More studies are needed to expand on these non-motor symptoms in marmosets in the longer-term, and perhaps, include other nonhuman primates at the SNPRC like macaques and baboons.”

During an epidemic in 2014, the Ebola virus claimed more than 11,000 lives in West Africa. Now, a new outbreak of the deadly disease threatens residents in eastern Democratic Republic of the Congo. While there isn’t yet a cure for Ebola, scientists at Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute recently made two discoveries that could help us understand how the virus infects the body.

In the first study, Staff Scientist Olena Shtanko, PhD studied a cellular pathway called “autophagy,” which means “self-eating.” This pathway normally occurs inside the cell and destroys invading foreign material or recycles necessary nutrients. But Dr. Shtanko’s team, working with a live Ebola virus, discovered, to their surprise, that autophagy was also active near the surface of the cell.

The Ebola virus exploits autophagy to induce another process to gain entry to the cell. That process is macropinocytosis, a poorly understood mechanism during which the cell surface remodels to form membrane extensions around virions (virus particles), eventually closing to bring them into the interior of the cell. It is as if the cell reaches out and grabs the virus, bringing it inside its membrane, where virus proteins can begin to replicate.

“We were stunned to find that Ebola virus is using autophagy regulators right at the surface of the cell,” Shtanko stated. “Knowing that these mechanisms work together, we can start finding ways to regulate them.”

Shtanko believes that drugs targeting the interplay between the two processes could potentially be developed to treat Ebola and other health conditions not associated with viruses. The regulation of the autophagy proteins could be used to fight complex diseases where macropinocytosis is disrupted, such as cancer and Alzheimer’s.

Shtanko’s commitment to fighting Ebola has spanned multiple studies. Another team she worked with discovered the interaction between an Ebola virus protein and a protein in human cells. This interaction may be a key part of replication of the killer disease in human hosts.

During the study, researchers tested whether the interaction between an Ebola virus protein called VP 30 and a host (human) protein called RBBP6 influenced the life cycle of the virus. By removing RBBP6 or flooding the cell with it, the scientists found striking results.

When RBBP6n was removed, viral replication went up exponentially compared to when the protein was present. Shtanko said this interaction is significant because if scientists can figure out the process behind this replication, they can potentially manipulate it and stop the disease progression.

Both of these discoveries represent large leaps forward in understanding the Ebola virus and treating and preventing this deadly disease.

Young macaques form an important part of our work at the NPRCs, helping us discover new ways of treating deadly diseases like tuberculosis, HIV/AIDS, Zika and more. Two researchers at Southwest NPRC at Texas Biomed recently went the extra mile to ensure these baby monkeys had a place to call their own.

https://www.kens5.com/video/news/local/eradicating-tuberculosis-with-the-help-of-macaques/273-4c1dd11c-90e8-40bf-9f51-16157308fe1f