In August 2018, Texas Biomedical Research Institute President and CEO Larry Schlesinger, MD named Deepak Kaushal, PhD, the new Director of the Southwest National Primate Research Center (SNPRC).

Dr. Kaushal joined SNPRC in January 2019, succeeding the retiring Robert Lanford, PhD As Director of SNPRC, Dr. Kaushal will be responsible for leading a national scientific resource funded by a $40 million National Institutes of Health grant and a team of nearly 150 scientists, veterinarians and animal care professionals.

Dr. Kaushal joins SNPRC after his tenure as Director of the Center for Tuberculosis Research within the Tulane National Primate Research Center (TNPRC) in Covington, La., and Professor in the Department of Microbiology and Immunology at Tulane University School of Medicine in New Orleans.

“We are excited Dr. Kaushal will be joining the Texas Biomed and SNPRC team,” Dr. Schlesinger said. “He is a world-renowned researcher whose focus in tuberculosis and HIV, specifically using nonhuman primates in TB research, is a natural fit with the Institute’s long-term vision of becoming the world leader in infectious disease research.”

Dr. Kaushal brings more than 25 years of experience working to eradicate tuberculosis, which kills more than two million people worldwide each year. Using the macaque nonhuman primate model, Dr. Kaushal’s lab tests new vaccine candidates and new drugs against the disease. A major focus of his research is to study the synergy between TB and HIV-AIDS.

“The opportunity to work in San Antonio is tremendous,” Dr. Kaushal said. “The community has a strong health science center and medical school, a network of higher education that fuels the engine of a research enterprise, strong non-profit organizations such as the Southwest Research Institute and is a vibrant, multicultural city. This is a place where technology, industry and supported research in infectious diseases can grow.”

A Bill and Melinda Gates Foundation supported researcher, Dr. Kaushal brings a portfolio of about $25 million in grant funding to SNPRC and Texas Biomed. He has authored more than 94 journal publications that have been published, are in press, in review or in revision and has presented at more than 66 scientific conferences worldwide.

He holds a PhD in biochemistry and microbiology from the University of Delhi in India and is a member of the Infectious Diseases Society of America, the American Society for Biochemistry and Molecular Biology, the Bill and Melinda Gates Foundation Collaboration for TB Vaccine Discovery (CTVD), the Bill and Melinda Gates Foundation working group on Nonhuman Primate Models and the AIDS Clinical Trials Group (ACTG).

Tuberculosis (TB) is the leading cause of death in AIDS patients. Unfortunately, no one knows exactly why the disease is such a significant threat in people with immune systems compromised by the HIV virus.

But researchers at the University of Pittsburgh and the University of Wisconsin–Madison recently reported in Infection and Immunity that a new nonhuman primate model using Mauritian cynomolgus macaques may help bring scientists closer to understanding the AIDS-TB link. The immune systems of these animals are similar to humans, and they are susceptible to both SIV (the nonhuman primate version of HIV) and Mycobacterium tuberculosis (which causes TB).

The paper’s authors included Shelby O’Connor, associate professor of pathology and laboratory medicine at UW–Madison and the Wisconsin National Primate Research Center (WiNPRC), and researchers from the University of Pittsburgh and WiNPRC.

The researchers used 15 macaques in the study. Of the eight monkeys infected with only M. tuberculosis, four animals survived more than 19 weeks following infection. In stark contrast, the researchers found that that all seven animals previously infected with SIV exhibited rapidly progressive TB following co-infection with M. tuberculosis and all had to be humanely euthanized after 13 weeks.  

“Our study demonstrated that pre-existing SIV dramatically diminishes the ability to control M. tuberculosis co-infection from the start,” said Mark Rodgers, senior research specialist at the University of Pittsburgh and the study’s lead author.

Senior author Charles Scanga, research associate professor of microbiology and molecular genetics at the University of Pittsburgh, added that this finding has much larger implications for research into the AIDS-TB link.

“For the first time, we have a well-characterized nonhuman primate model that will facilitate research into vaccines or therapeutics to battle TB in people living with HIV,” he said.

The theme for the 2018 World AIDS Day (December 1) is “Saving Lives through Leadership and Partnerships,” which closely aligns with National Primate Research Center (NPRC) efforts to improve therapies to treat people who are living with HIV/AIDS and to develop a vaccine that is safe and effective against all strains of the virus.

For more than 30 years, the NPRCs have led the way toward understanding and fighting HIV. The virus infects and kills millions globally; just last year, approx. 36.9 million people worldwide were living with HIV, and the death toll from AIDS-related illnesses had reached 940,000.

HIV treatments have come a long way since the disease turned pandemic and poured into the public consciousness in the mid-1980s. Today, because of the antiretroviral drug cocktails available to treat the virus, HIV is no longer a death sentence in most developed countries. Yet the hunt for better treatments and a vaccine continues.

One potential treatment making headlines involves broadly neutralizing monoclonal antibodies (bNAbs). These antibodies are isolated from individuals who have the rare ability to neutralize a majority of evolutionarily diverse HIV-1 field isolates after years of chronic infection.

NPRC scientists are part of multiple large research collaborations working on moving these bNAbs from research labs to doctors’ offices. To achieve this, the scientists have extracted these special antibodies from human blood, grown them in lab dishes and infused them into monkeys that have simian immunodeficiency virus, or SHIV, a chimeric version of the AIDS virus.

Based on the encouraging results of the monkeys being able to control their viral loads, researchers are moving bNAbs into human clinical trials. If successful, the treatment could mean fewer lifelong medications for people with HIV. This is exciting news for the scientists who have devoted decades of basic research to gain understanding of this complex, insidious and ever-shifting virus.

The NIH Office of Research Infrastructure Programs (ORIP), which supports the NPRCs, and the National Institute for Allergy and Infectious Diseases (NIAID) have been leading supporters of animal-based AIDS research, thus making possible the NPRCs’ research involving hundreds of dedicated scientists, veterinarians, animal care personnel, technicians, students and more.

On World AIDS Day today, the NPRCs express our support for people who are living with HIV, remember those who have died from an AIDS-related illness and thank our employees for their commitment that is bringing us closer to the day when the HIV/AIDS global health challenge is a distant memory.

November 6, 2018 marks the 20th anniversary of the seminal paper “Embryonic stem cell lines derived from human blastocysts,” published in Science. The paper documented a breakthrough that occurred when University of Wisconsin-Madison and WiNPRC scientist James Thomson, VMD, PhD, developed a technique to successfully isolate and culture human embryonic stem cells from patient-donated, lab-fertilized embryos.

Thomson was successful again in 2007 when he became the first to grow induced pluripotent stem cells. Induced pluripotent stem cells behave similarly to embryonic stem cells with their source being genetically reprogrammed mature cells, such as skin cells. Thomson derived this type of cell with WiNPRC scientist Junying Yu, publishing again in Science.

Scientists predicted both of these cell types could someday be useful for drug discovery and transplant medicine. Today, those predictions are coming true.

Embryonic and induced pluripotent stem cells can become virtually any cell in the body. Scientists and doctors study these cells and their derivatives to learn more about basic biology and genetic origins of disease. They also use them for cell, tissue and organ transplant studies, as well as for pharmaceutical testing and studying the effects of environmental toxins on human cells and tissues.

Both types of stem cells, which Thomson and other NPRC scientists advanced from rodents to nonhuman primates and then to humans in the 1990s, are already in early clinical trials for macular degeneration, spinal cord injury, heart disease, ALS and more. There are currently 27 clinical trials around the world involving embryonic stem cells and their derivatives. Another 42 trials involve the use of induced pluripotent stem cells.

These discoveries underscore the importance of basic science and are excellent examples of how basic science can lead to applied science, clinical trials, entrepreneurship and expanding business and industry. Globally, the market for products related to stem cell discoveries is projected to reach more than $270.5 billion by 2025, according to a 2017 Transparency Market Research report.

A whole new era of science and medicine sprung from those early 1990s discoveries with nonhuman primates. The NPRCs continue to advance research in both human and nonhuman primates involving embryonic stem cells, induced pluripotent stem cells, tissue-specific (adult) stem cells and gene editing of both stem cells and mature cells. We look forward to the cell and regenerative medicine discoveries that are still to come!

Parkinson’s disease is most widely known for causing muscle tremors and motor-control symptoms, but most Parkinson’s sufferers also exhibit damage to their hearts’ connection to the sympathetic nervous system. In fact, that damage is one of the first signs of Parkinson’s, but the connection is often not made until the more visible symptoms develop.

Researchers at the Wisconsin National Primate Research Center (WiNPRC) and the University of Wisconsin (UW-Madison) have found a new way to examine stress and inflammation in the heart that could serve as an early indicator of Parkinson’s well before the more common symptoms begin.

The heart damage is significant because it contributes to a tendency for Parkinson’s patients to suffer physical injury as a result of blood pressure fluctuations.

“This neural degeneration in the heart means patients’ bodies are less prepared to respond to stress and to simple changes like standing up,” said Marina Emborg, a University of Wisconsin–Madison professor of medical physics and Parkinson’s researcher at the WiNPRC. “They have increased risk for fatigue, fainting and falling that can cause injury and complicate other symptoms of the disease.”

The sympathetic nervous system signals the heart to accelerate its pumping to match quick changes in activity and blood pressure. Researchers at WiNPRC developed a method for tracking the mechanisms that cause the damage to heart nerve cells, then tested the method in the nervous system and heart of monkeys.

Ten rhesus macaque monkeys served as models for Parkinson’s symptoms, receiving doses of a neurotoxin that caused damage to the nerves in their hearts in much the same way Parkinson’s affects human patients. Once before and twice in the weeks after, the monkeys underwent PET scans, a medical imaging technology that can track chemical processes in the body using radioactive tracers.

The UW–Madison researchers used three different tracers to map three different things in the left ventricle of the monkeys’ hearts: where the nerves extending into the heart muscle were damaged, where the heart tissue was experiencing the most inflammation, and where they found the most oxidative stress.

The scans were accurate enough to allow the researchers to focus on changes over time in specific areas of the heart’s left ventricle.

“We know there is damage in the heart in Parkinson’s, but we haven’t been able to look at exactly what’s causing it,” said researcher Jeannette Metzger. “Now we can visualize in detail where inflammation and oxidative stress are happening in the heart, and how that relates to how Parkinson’s patients lose those connections in the heart.”

By tracing the progression of nerve damage and its potential causes, the radioligands can also be used to test potential new treatments. The researchers gave half the monkeys in the study a drug, pioglitazone, that has shown promise in protecting central nervous system cells from inflammation and oxidative stress.

“The recovery of nerve function is much greater in the pioglitazone-treated animals,” added Emborg. “And what’s interesting is this method allows us to identify very specifically the differences the treatment made—separately for inflammation and for oxidative stress—across the heart.”

The heart problems opened to examination by the new imaging methods are not limited to Parkinson’s disease. Heart attacks, diabetes and other disorders cause similar damage to nerves in the heart, and those patients and potential therapies could also benefit from the new visualization method.

The results suggest human patients could benefit from the radioligand scans, and Metzger wonders if it could help catch some Parkinson’s patients before their other symptoms progress.

Stress can lead to a host of health issues, including heart disease, digestive problems, asthma and diabetes. Stress can also be inherited, setting up infants and children for lives of anxiety as a result of stressors their parents faced before they were even conceived.

Fortunately, researchers at Emory University’s Yerkes National Primate Research Center have shown for the first time it is possible to reverse the hereditary influences of parental stress. The findings could lead to treatments to prevent intergenerational stress in humans.

The scientists used two pleasant odors on adult male mice to identify effective strategies to break the cycle of intergenerational stress. They began the study with each mouse participating in one of three protocols: 1) exposed the mice to an odor; 2) trained the mice to associate an odor with a mild stressor; or 3) trained the mice to associate the odor with a mild stressor and then extinguished the fear via extinction training during which the researchers presented the odor in the absence of any stress.

By extinguishing parental fear to the two specific odors, the researchers found three key results: 1) the offspring did not show any behavioral sensitivity to the same two odors; 2) the nervous systems of the offspring did not show any structural imprints of the parental olfactory stress; and 3) the sperm of the parental male mice did not bear chemical imprints of the olfactory stress.

“Our study results not only confirm conditioned stress can be extinguished in the parent without passing it on to the offspring, they are an important public health contribution because they provide optimism for applying similar interventional approaches in humans and breaking intergenerational cycles of stress,” said Brian Dias, an assistant professor at the Yerkes Research Center and the Emory University School of Medicine Department of Psychiatry and Behavioral Sciences. “These latest data provide our research team a platform from which we can address larger public health concerns, including the intergenerational influences of parental neglect and maltreatment during childhood. We want to know whether reversals such as what we showed in our current study can be observed after we apply interventions to populations exposed to these negative environmental influences.”

For most of us, getting a flu shot ranks among the least exciting annual events. But researchers at the Washington National Primate Research Center (WaNPRC) at the University of Washington (UW) are hoping to make this yearly obligation a thing of the past.

A team led by Deborah Fuller, a professor in the Department of Microbiology at the UW School of Medicine, is testing the effectiveness of a universal vaccine that protects from every strain of influenza virus, even when the viruses transform genetically from year to year. Working with cynomolgus macaques, the researchers have seen promise using a DNA vaccine that instructs skin cells to produce antigens, while inducing antibodies and T cell responses to fight flu infection.

The vaccine was created using genetic components of influenza virus that remain constant. This feature allows the vaccine to get around the genetic drift, or changes, that occur in influenza strains from year to year.

“With the immunized groups, we found that using this conserved component of the virus gave them 100 percent protection against a previous circulating influenza virus that didn’t match the vaccine,” Fuller said. “This was very exciting for us.”

The DNA vaccine is administered through the epidermis with a “gene gun” device, which injects the vaccine directly into the skin cells. The cells then produce the flu vaccine and prompt the body to actively fight infection. This is an improvement over current on-the-market vaccines, which simply repel the virus.

This approach also takes less time to produce—about three months—than the nine months required to produce the current U.S.-approved vaccine.

“We’ve been working essentially with the same vaccine (techniques) over the last 40 years,” Fuller noted. “It’s been a shake-and-bake vaccine: You produce the virus, you kill the virus, you inject it. Now it’s time for vaccines to go through an overhaul, and this includes the influenza vaccine.”

Fuller said that this kind of universal vaccine could eliminate the need for yearly flu vaccinations and be kept on-hand for rapid deployment in response to a deadly pandemic strain of the virus.

She added that DNA-based vaccines may also prove effective for different viruses, like Zika, and for other possible serious outbreaks.

Can a promising cancer drug also treat tuberculosis (TB), the world’s single deadliest infectious disease? Researchers at the Texas Biomedical Research Institute, host institution for the Southwest National Primate Research Center, think so.

The team discovered a mechanism for regulating cell death – called apoptosis – that could help control the bacterial infection that causes TB. Dr. Eusondia Arnett and her colleagues tested this concept by infecting human immune cells called macrophages with the TB bacterium, then treating those infected cells with the potential cancer treatment. The result was an 80% reduction in the growth of the TB bacterium.

“Induction of apoptosis and subsequent reduced growth of the TB bacterium should ultimately result in less inflammation and damage to the lungs, and increased control of TB,” said Dr. Arnett.

One-fourth of the world’s population is infected with TB, according to the Centers for Disease Control and Prevention, including 9,000 new cases in the United States in 2017. Up to 13 million people in America carry the latent TB infection, with 5-10% developing infectious TB in their lifetimes. (The majority of those infected were born outside the U.S. and infected prior to arriving in the country from areas of the world where TB is more common.)

TB infection also creates dense cellular structures, called granulomas, in the lungs of infected persons. Granulomas are the body’s attempt to wall off an infection it is unable to eliminate. But they also provide a niche for the bacteria to become resistant to antibiotics. Dr. Arnett’s study showed that these experimental cancer drugs also reduced TB bacteria growth in granulomas in a human model, holding promise for these drugs in humans and animals.

Dr. Larry Schlesinger, President and CEO of Texas Biomed, said this finding highlights the critical role of basic scientific research.

“When we study important host cell pathways for disease, we can find relationships we didn’t even know existed,” he explained. “We can forge new ways to use current knowledge to create novel strategies for therapy for infection to be used along with antibiotics.”

The drugs used in this study are already in Phase II of Food and Drug Administration clinical trials. The next step for testing the drugs’ effectiveness in treating TB is a mouse model, followed by nonhuman primate models and ultimately, human clinical trials.

Cytomegalovirus, or CMV, is a common virus found in almost every person on the planet. For most of them, it causes no harm and leads to no symptoms. But for newborn babies and people with compromised immune systems, it can lead to birth defects, serious illness and even death.

Now, researchers associated with the California National Primate Research Center (CNPRC) at the University of California, Davis have discovered that low levels of CMV changed microbe and immune cell populations and response to the flu vaccine in rhesus macaques. CMV infection generally increased immune activity but also diminished antibodies responding to influenza vaccination. The study also found that low levels of CMV make the body susceptible to changes in environmental conditions that could accentuate their impact.

“Subclinical CMV infection alters the immune system and the gut microbiota in the host and that impacts how we respond to vaccines, environmental stimuli and pathogens,” said Satya Dandekar, who chairs the Department of Medical Microbiology and Immunology at UC Davis and is a core scientist in the infectious diseases unit at CNPRC at UC Davis. “This study highlights the role of these silent, latent viral infections that are totally asymptomatic.”

The researchers believe that these low-level CMV infections may be one reason for the variation in response to vaccines across large populations. One possibility is that the immune system’s constant effort to control CMV might be diverting resources that it might direct to other threats.

The next step in the process will be testing other vaccines in CMV-infected animals and generally working to better understand how subclinical viruses affect the immune system.

“This highlights the impact silent viruses have to influence how the host responds to vaccines,” said Dandekar. “Can we somehow use this information to optimize our immune system? That’s the direction we would like to go to see how we can inhibit CMV to see if we can enhance the vaccine response.”

Reviewed August 2019

Anxiety disorders affect some 40 million Americans; more than 16 million Americans suffer from depression, according to the Anxiety and Depression Association of America. Researchers at the University of Wisconsin–Madison and the Wisconsin National Primate Research Center (WiNPRC) have discovered brain pathways in juvenile monkeys that may lead to the development of anxiety and depression later in life.

Extreme early life anxiety is a significant risk factor for anxiety disorders and depression in humans, and discovering a connection between two areas of the brain that are connected to anxious temperament in pre-adolescent rhesus macaques could be a significant breakthrough.

“We are continuing to discover the brain circuits that underlie human anxiety, especially the alterations in circuit function that underlie the early childhood risk to develop anxiety and depressive disorders,’’ said Ned Kalin, MD, chair of the psychiatry department at UW–Madison.

“In data from a species closely related to humans, these findings strongly point to alterations in human brain function that contribute to the level of an individual’s anxiety. Most importantly these findings are highly relevant to children with pathological anxiety and hold the promise to guide the development of new treatment approaches.”

The study used functional magnetic resonance imaging (fMRI) to study the connections between two regions of the brain. It builds on the group’s earlier study that used positron emission tomography (PET) scans to study metabolism in the same circuitry; fMRI detects oxygenation changes in blood while PET measures neuronal metabolic activity. Taken together, said Jonathan Oler, PhD, the study’s co-lead author, the new findings demonstrate that the degree of synchronization between these brain regions is correlated with anxious temperament.

“When we began this research, we knew so little about the brain regions involved, especially in primate species,’’ Oler says. “This study speaks to how important it is to study animals that are related to humans as they allow us to learn about the causes of human anxiety and by so doing we can potentially develop better treatment and hopefully prevention strategies.”

Oler and Kalin say their analysis suggests that the same genes that underlie the connectivity of this circuit also underlie anxious temperament. Studies underway in the Kalin laboratory are aimed at identifying gene alterations in the anxiety-related brain regions, and have the potential to lead to new treatments that are directed at the cause of anxiety rather than just the symptoms.