February 22, 2023

The immune system has long been touted as the body’s primary defense against invading viruses, with the understanding that a strong immune response swiftly knocks out an infection while a weak one allows it to linger, leading to prolonged disease or even death.

Now, researchers at Tulane University are looking at an entirely different system—the body’s ability to use nutrients at a cellular level — to predict disease response and severity.

Tulane immunologist Clovis Palmer, PhD, studies metabolic changes resulting from viral infections. In a literature review published in Nature Metabolism, Palmer analyzed a body of evidence that looked at the metabolic changes that occur in cells when viral invaders, such as HIV, hepatitis B, or SARS-CoV-2, pose a threat.

Palmer concluded that the way in which cells, even non-immune cells, use nutrients in the presence of a viral pathogen can determine disease outcome and severity in the earliest stages of infection, or even long after the pathogen leaves the body.

Certain molecules on the surface of a cell determine how nutrients are used. These allow nutrients like glucose and fat to facilitate energy production or, if necessary, mount an offense against invading pathogens. Under these conditions, nutrients strengthen and bolster the cell. But viral pathogens can also hijack these surface molecules to gain entry into the cell and then use the nutrients to replicate.

“Whether nutrients are used to strengthen and defend the cell or are hijacked by the virus depends on conditions in the host like older age, nutritional status and obesity,” Palmer said. “We saw that these were all significant risk factors for the worst outcomes of COVID but didn’t really know what was driving it.”

Understanding how cells use nutrients in the presence of viral pathogens at the earliest states of infection is key to the development of treatments that can strengthen the cell, not the virus. While most antiviral medications take aim at the virus, Palmer seeks to prevent or lessen disease by keeping the nutrients on the cell’s side.

Palmer is working with Jay Rappaport, PhD, director of the Tulane National Primate Research Center and professor of microbiology and immunology at the Tulane University School of Medicine, on rewiring metabolic response in nonhuman primate models of COVID and HIV to prevent and treat long-term symptoms.

“We know that when metabolism is impaired, there is increased susceptibility to infection,” said Rappaport. “Modulating the metabolic response has vast implications for all infectious diseases, from optimizing immunity to mitigating the effects of aging, autoimmunity, and other drivers of disease.”

September 6, 2022

According to the CDC, there are currently 83,949,036 cases of Covid-19 reported in the United States. We all know someone who has been through Covid-19. Headaches, runny nose, congestion, and losing the ability to taste food are common symptoms. But, until now, there have remained many questions surrounding how COVID-19 affects the central nervous system—especially in patients who haven’t experienced a lot of respiratory symptoms. 

 

While damage to the central nervous system is increasingly evident, the origin remains unclear. Understanding the effects will ultimately help discover and implement future treatments.

 

Recently, researchers at Tulane University evaluated the neuropathology damage associated with SARS-CoV-2 infection in a nonhuman primate. As it turns out, severe brain inflammation and injury consistent with reduced blood flow or oxygen to the brain, including neuron damage, death, and more, are consistent markers, especially with primates who had little to no respiratory issues. These findings are also compatible with ones reported on autopsied human brains who died from a SARS-CoV-2 infection.

 

Dr. Tracy Fischer, lead investigator and associate professor of microbiology and immunology at the Tulane National Primate Research Center, states, “Because the subjects didn’t experience significant respiratory symptoms, no one expected them to have the severity of disease that we found in the brain. But the findings were distinct and profound, and undeniably a result of the infection.”

 

Note: The NPRCs will update this blog with our latest COVID-19 news.

Since beginning COVID-19 research in early 2020, NPRC researchers have made encouraging progress in efforts to better understand, diagnose, prevent and treat this novel disease. We’re committed to conducting and enabling research to end this global pandemic and to providing information so the public has ready access to our scientific results.

Our most recent COVID-19 news includes: 

Below is even more information about our extensive and collaborative COVID-19 research:

Diagnostics:

Prevention:

Treatments:

Additional NPRC COVID-19 News:

Bookmark this page so you can easily return here for the latest NPRC COVID-19 research information. We’ve also compiled a list of resources here and provided links to previous NPRC COVID-19 news and national media stories here.

July 20, 2021

Lyme disease, also known as Lyme borreliosis, is an infectious disease caused by Borrelia burgdorferi bacterium, which is spread by ticks. The most common sign of infection is a red rash that appears at the site of the tick bite. Other signals of Lyme include flu-like symptoms, joint pain and weakness in the limbs.

After a 69-year-old woman was diagnosed and repeatedly treated for Lyme disease for 15 years before her death, researchers at the Tulane National Primate Research Center who had previously discovered the persistence of B. burgorferi  despite antibiotic therapy found that the same bacterium was still intact upon autopsy. 

In addition to the typical symptoms of Lyme, she experienced continual neurological decline, including a severe movement disorder and personality changes. The woman eventually passed away after being diagnosed with Lewy body dementia— a disease that presents itself with similar declined motor functions of Parkinson’s Disease with the added element of significant memory issues.  

The Tulane research team found that her central nervous system (CNS) still harbored intact spirochetes despite aggressive antibiotic therapy for Lyme disease at different times throughout her illness. The findings may lead to a correlation between Lyme disease and Lewy body dementia.

“These findings underscore how persistent these spirochetes can be in spite of multiple rounds of antibiotics targeting them,” said Monica Embers, associate professor of microbiology and immunology at Tulane. “We will be interested in investigating the role that B. burgdorferi may play in severe neurological disease, as this is an area of research that has not yet been fully explored.”

To learn more about research being done by Tulane NPRC, please visit here.

April 27, 2021

Did you know the rhesus macaque is the most widely studied nonhuman primate in biomedical research? The U.S. research colonies of rhesus macaques were founded primarily with animals imported from India decades ago and with the addition of Chinese-origin rhesus macaques over time. A deep understanding of their evolution and genetics is key to recognizing the origins of human traits and identifying disease genes of value to improving human health.

Rhesus macaques at the seven National Primate Research Centers (NPRCs) are key in the discovery and development of new and robust models of human disease and in evaluating the effect of genetic variation on experimental treatments prior to human clinical trials.  

In a recent publication in Science that detailed researchers’ use of advanced sequencing technology and analysis of more than 850 macaques across the seven NPRCs, researchers present a complete reference genome for the rhesus macaque. “In particular, we can now finally tackle some of the more complex regions of the genome and begin to understand how new genes evolve including the processes that have shaped them,” says University of Washington genome sciences professor and senior author in the paper, Evan Eichler, PhD.

In addition, the study identified animals that naturally carry potentially damaging genetic mutations, allowing researchers to better understand genetic variation and susceptibility to diseases of relevance to humans. So far, the findings reveal thousands of naturally occurring genetic variants (mutations), including those in genes linked to Autism Spectrum Disorder and other neurodevelopmental disorders in humans, such as SHANK3.

Jeffrey Rogers, PhD, associate professor at the Human Genome Sequencing Center and Department of Molecular and Human Genetics at Baylor College of Medicine and co-author of the paper explains, “Rhesus macaques are important for studies of conditions ranging from infectious disease (including COVID-19) to neuroscience, cancer and reproductive biology. A high-quality reference genome can aid researchers who are looking to understand the causes of various illnesses or aiming to develop treatments.”

The study is a great example of a broad collaboration across the NPRCs and other research centers in the U.S. that will continue to make a difference in human health. By identifying rhesus macaques that carry naturally occurring mutations, NPRC and other researchers are now able to examine biobehavioral traits associated with mutations. The researchers can also follow the monkeys’ offspring, and, in some cases, actually create new breeding groups to generate animals with specific genetic mutations and phenotypes. 

“This new information will lay the foundation for us to create naturally occurring models of human genetic diseases,” says Paul Johnson, MD, director of the Yerkes (now Emory) NPRC. “The development of these new models could have a profound impact on our ability to translate research in animal models into treatments and cures in people,” he continues.

To learn more about NPRC advances in genetics and genomics, explore additional research here

March 3, 2021

Scientific discovery is an ongoing process that takes time, observation, data collection and analysis, patience and more. At the NPRCs, our recent COVID-19 research is an example of the ongoing basic science process — how current research builds on previous discoveries and how discoveries help improve human health. This article from the National Institutes of Health (NIH) explains why basic science, such as the NPRCs conduct, is important and how taking time, as long as it takes, is a necessary part of scientific discovery.

Discoveries in Basic Science: A Perfectly Imperfect Process

Have you ever wondered why science takes so long? Maybe you haven’t thought about it much. But waiting around to hear more about COVID-19 may have you frustrated with the process.

Science can be slow and unpredictable. Each research advance builds on past discoveries, often in unexpected ways. It can take many years to build up enough basic knowledge to apply what scientists learn to improve human health.

“You really can’t understand how a disease occurs if you don’t understand how the basic biological processes work in the first place,” says Dr. Jon Lorsch, director of NIH’s National Institute of General Medical Sciences. “And of course, if you don’t understand how the underlying processes work, you don’t have any hope of actually fixing them and curing those diseases.”

Basic research asks fundamental questions about how life works. Scientists study cells, genes, proteins, and other building blocks of life. What they find can lead to better ways to predict, prevent, diagnose, and treat disease.

How Basic Research Works

When scientists are interested in a topic, they first read previous studies to find out what’s known. This lets them figure out what questions still need to be asked.

Using what they learn, scientists design new experiments to answer important unresolved questions. They collect and analyze data, and evaluate what the findings might mean.

The type of experiment depends on the question and the field of science. A lot of what we know about basic biology so far has come from studying organisms other than people.

“If one wants to delve into the intricate details of how cells work or how the molecules inside the cells work together to make processes happen, it can be very difficult to study them in humans,” Lorsch explains. “But you can study them in a less complicated life form.”

These are called research organisms. The basic biology of these organisms can be similar to ours, and much is already known about their genetic makeup. They can include yeast, fruit flies, worms, zebrafish, and mice.

Computers can also help answer basic science questions. “You can use computers to look for patterns and to try to understand how the different data you’ve collected can fit together,” Lorsch says.

But computer models have limits. They often rely on what’s already known about a process or disease. So it’s important that the models include the most up-to-date information. Scientists usually have more confidence in predictions when different computer models come up with similar answers.

This is true for other types of studies, too. One study usually only uncovers a piece of a much larger puzzle. It takes a lot of data from many different scientists to start piecing the puzzle together.

Building Together

Science is a collective effort. Researchers often work together and communicate with each other regularly. They chat with other scientists about their work, both in their lab and beyond. They present their findings at national and international conferences. Networking with their peers lets them get feedback from other experts while doing their research.

Once they’ve collected enough evidence to support their idea, researchers go through a more formal peer-review process. They write a paper summarizing their study and try to get it published in a scientific journal. After they submit their study to a journal, editors review it and decide whether to send it to other scientists for peer review.

“Peer review keeps us all informed of each other’s work, makes sure we’re staying on the cutting-edge with our techniques, and maintains a level of integrity and honesty in science,” says Dr. Windy Boyd, a senior science editor who oversees the peer-review process at NIH’s scientific journal of environmental health research and news.

Different experts evaluate the quality of the research. They look at the methods and how the results were gathered.

“Peer reviewers can all be looking at slightly different parts of the work,” Boyd explains. “One reviewer might be an expert in one specific method, where another reviewer might be more of an expert in the type of study design, and someone else might be more focused on the disease itself.”

Peer reviewers may see problems with the experiments or think different experiments are needed. They might offer new ways to interpret the data. They can also reject the paper because of poor quality, a lack of new information, or other reasons. But if the research passes this peer review process, the study is published.

Just because a study is published doesn’t mean its interpretation of the data is “right.” Other studies may support a different hypothesis.

Scientists work to develop different explanations, or models, for the various findings. They usually favor the model that can explain the most data that’s available.

“At some point, the weight of the evidence from different research groups points strongly to an answer being the most likely,” Lorsch explains. “You should be able to use that model to make predictions that are testable, which further strengthens the likelihood that that answer is the correct one.”

An Ever-Changing Process

Science is always a work in progress. It takes many studies to figure out the “most accurate” model—which doesn’t mean the “right” model.

It’s a self-correcting process. Sometimes experiments can give different results when they’re repeated. Other times, when the results are combined with later studies, the current model no longer can explain all the data and needs to be updated.

“Science is constantly evolving; new tools are being discovered,” Boyd says. “So our understanding can also change over time as we use these different tools.”

Science looks at a question from many different angles with many different techniques. Stories you may see or read about a new study may not explain how it fits into the bigger picture.

“It can seem like, at times, studies contradict each other,” Boyd explains. “But the studies could have different designs and often ask different questions.”

The details of how studies are different aren’t always explained in stories in the media. Only over time does enough evidence accumulate to point toward an explanation of all the different findings on a topic.

“The storybook version of science is that the scientist is doing something, and there’s this eureka moment where everything is revealed,” Lorsch says. “But that’s really not how it happens. Everything is done one increment at a time.”

 

February 23, 2021

Is gene editing the answer scientists have been looking for to eliminate diseases such as HIV?  

A research team at Temple University and Tulane National Primate Research Center (TNPRC) has focused  on removing DNA from viruses, one of the main ways  a virus survives treatments. Now, they’ve seen promising results  that may lead to a cure for HIV.  

The team has employed CRISPR technology, best described as “molecular scissors,” which can precisely cut and remove specific segments of DNA. When attached to a mild adeno-associated virus, these gene editing shears can be sent into the body to cut and remove  DNA from viruses, including HIV.  

They tested this on nonhuman primates infected with  simian immunodeficiency virus (SIV), a disease genetically similar  to HIV, and observed that the  gene editing molecules were able to enter SIV viral reservoirs in the lymph, spleen, bone marrow and brain to prevent the cells from making new virus within these reservoirs. 

Within just three weeks, the new treatment had eliminated nearly two-thirds of the virus that had managed to resist the antiretroviral therapy (ART) many HIV patients receive.  

Andrew MacLean, PhD, one of the principal investigators of the research project and associate professor of microbiology and immunology at TNPRC, views this as evidence a cure for HIV is a real possibility. 

“This is an important development in what we hope will be an end to HIV/AIDS,” MacLean said. “The next step is to evaluate this treatment over a longer period to determine if we can achieve complete elimination of the virus, possibly even taking subjects off of ART.” 

Co-corresponding author also includes Dr. Binhua Ling, one of the principal investigators of the research and previous associate professor of microbiology and immunology at TNPRC. Ling is currently an associate professor at Texas Biomedical Research Institute. 

A potential cure for HIV is just the beginning though. These “molecular scissors” will likely play a role in future efforts to cure diseases currently receiving treatments to make them manageable.  

The results are indeed promising, but the work of the NPRCs is never over. They will continue searching for the causes, preventions, treatments and cures leading to longer, healthier lives worldwide. Learn more about our HIV-related studies by visiting this link.   

December 15, 2020

Research with animals is crucial to improving human and animal health. Animals in research provide unique insights not available with other scientific models, and they help scientists determine safety and effectiveness of preventions, treatments and cures. During the COVID-19 pandemic, animals in research have been especially important in accelerating the development COVID-19 vaccines as well as better diagnostics and additional treatment options.

At the NPRCs, we’re helping fill a critical role in halting COVID-19 by leading NIH-funded studies at our centers. We’re also participating in the public-private partnership ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) to develop treatments and vaccines by sharing our knowledge, resources and animals, including conducting preclinical studies with NPRC monkeys for some of the leading industry vaccine candidates.

Scientific collaboration is especially important during a pandemic when time is of the essence and, in this case, animal resources are limited. At the onset of the pandemic, monkey importation was halted, putting increasing demands on the NPRC animal colonies, which were already limited in quantity and availability. The NPRCs account for only 1 in every 5 nonhuman primates (NHPs) used in U.S.-based research, so the limited supply at a time of high demand impacts NPRC COVID-related studies as well as pre-pandemic studies under way at the NPRCs and those in planning stages.

The NPRCs remain dedicated to our other areas of study, including research into HIV/AIDS and other infectious diseases, the neurosciences, cardiovascular and respiratory health, genetics and transplant medicine. 

We are also committed to meeting the future needs of animals for NIH-funded research. We are already growing our on-site breeding colonies when time, space and funding permit, strategically assigning animals to research protocols, harmonizing across centers for efficient use of animals and increasing rigor and reproducibility to facilitate collaboration and consistency across research labs. These strategic steps now further position the NPRCs for the translation of our research advancements from cell and animal models to humans, and are indicative of our commitment to help people across generations and the world live longer, healthier lives. 

To learn more about the NPRCs’ ongoing efforts to combat COVID-19, visit this page.

Editor’s Note, 2/22/21: The New York Times covered the research monkey shortage in today’s issue. Read the story here.

November 24, 2020

Talking about animals in research may not be part of everyday conversations – unless you work in research, are learning more about it or want to stop it. But if everyone knew how critical animals have been in 2020 to fast-track a safe and effective COVID-19 (coronavirus) vaccine, would that change?

Earlier this year, the National Institutes of Health (NIH) called upon the National Primate Research Centers (NPRCs) – as NIH has for HIV/AIDS, Ebola, Zika and other infectious disease threats – to identify animal species for studying the SARS-CoV-2 virus and developing safe and effective vaccines to block it.

The NPRCs went to work and within a few months had discovered how valuable nonhuman primate models (NHPs), especially macaques, are for studying SARS-CoV-2. The NPRCs found the virus infects rhesus, pigtail and cynomolgus macaques, so these animals were included in research programs that resulted in several vaccine candidates in the pipeline by summer’s end. In addition, other key models for SARS-CoV-2, such as mice and hamsters, contributed to the broadening knowledge of how best to tackle the disease in humans. This rapid pace of discovery was possible due to the NPRC researchers applying their expertise fighting other viruses, especially HIV/AIDS.

As with those other viruses, the NPRC researchers closely studied SARS-CoV-2 transmission routes and pathogenesis – this time focusing on the respiratory virus’ activity in the lungs and its impact on cells, tissues and organs. The researchers also conducted detailed genetic studies on the virus to help pharmaceutical researchers use pieces of the virus’ genetic code to fashion vaccine candidates and test them for safety and effectiveness in macaques.

Translating the biomedical research findings into the human population requires going from up to a few dozen monkeys in research to thousands of human volunteers in clinical trials; for COVID-19, more than 200,000 volunteers have enrolled in four promising clinical trials. As announced in November 2020, the Moderna and Pfizer mRNA vaccines tested on rhesus macaques were more than 90 percent effective in preventing COVID-19 in widespread (Phase 3) human clinical trials and are now on track for emergency FDA approval.

Research with animals connects these vaccines with other SARS-CoV-2 scientific advancements just as it has made connections among NPRC HIV/AIDS studies, the results from which facilitated the rapid pace to COVID-19 discoveries. Improving human and animal health – that’s what NPRC research with animals does, and that’s worth talking about any day.

Learn more about research with animals scientific advancements here.

November 10, 2020

Could a recent discovery about the body’s natural defenses be a stepping stone toward combating kidney-related health issues? Scientists say yes.

Macrophages are a type of white blood cell central to the immune system that detect and engulf harmful pathogens, like viruses, bacteria and fungi, serving as helpful scavengers to fight infections. They also cause or suppress inflammation and secrete molecules that allow communication between different cell types, all of which provide a healthy immune response in fighting infection and disease.

Scientists have long known the origins of different types of macrophages found in the brain, gut, heart and liver. The origins of those found in kidney tissue, however, are not as well understood. Until now, researchers hadn’t known if these macrophages had traveled from elsewhere in the body or if they were produced during embryonic development. As it turns out, both theories are correct.

In a recent study, Tulane National Primate Research Center (TNPRC) scientists Xuebin Qin, PhD, professor of medicine, and Fengming Liu, PhD, assistant professor of microbiology and immunology, made a new discovery about renal (kidney) macrophages that fundamentally changes the understanding of how these cells populate.

Using a new rapid cell ablation (destruction) technique created by Qin, the team discovered that in a mouse model, half of renal macrophages originate during the embryonic state and the other half derive from bone marrow. They also showed that embryo-derived renal macrophages have a stronger immune response than their bone marrow-derived counterparts. 

“These findings advance our current understanding of tissue-resident macrophages and may lead to promising new directions for the development of new therapeutics for kidney diseases,” explained Qin.

The implications of this discovery are important because while the kidneys help control the volume of blood in the body and maintain the proper concentrations of proteins and electrolytes, they are also subject to infection and disease. The role of macrophages in clearing any infection and supporting kidney function could prove key to future treatments of kidney disease and even infectious diseases that are associated with kidney failure, like human immunodeficiency virus (HIV) and coronavirus (COVID-19).

NPRC scientists across the country are working to combat infectious diseases through a variety of research projects. You can learn more about NPRC’s infectious disease studies at this link, as well as coronavirus-specific studies at this link.

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