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Ho Lab Develops “Targeted Long-Acting Combination Antiretroviral Therapy” (TLC-ART)

HIV team researchers, from left: Rodney Ho, Josefin Koehn, Sarah Lane, Lisa McConnachie, Jake Kraft, Loren Kinman, Jesse Yu and Wonsok Lee.

Investigators from the University of Washington schools of pharmacy and medicine have devised a long-acting therapy for HIV. The macaque model study acknowledged the support from former and current members of the RSS team at the Washington National Primate Research Center.

Researchers concluded that a simple, scalable three-drug combination of the HIV drugs tenofovir, lopinavir and ritonavir exhibited continual drug levels in host cells for the virus. These levels persisted for more than two weeks, marking a significant breakthrough. “Thus, TLC-ART101 could be considered for development as a long-acting, fixed-dose injectable combination for HIV treatment for adults and children.”

The findings were published in the March issue of the journal AIDS. Professors Rodney JY Ho of the School of Pharmacy and Ann Collier of the School of Medicine were lead authors; first author was Jake Kraft of the UW Department of Pharmaceutics. Read more at UW Medicine Newsroom, your source for news and information from the University of Washington Health Sciences and UW Medicine.

WaNPRC Core Staff Scientist and UW Alum Fights to Stop Zika

Photo by Rick Dahms

Professor Michael Gale heads a laboratory located in the burgeoning biomed research hub at the southern end of Lake Union in Seattle. His group has research programs focused on understanding immune control of West Nile virus infection and HIV infection as well as viral replication and infection outcomes of Hepatitis C. Gale and the 34 researchers in his lab are now in the process of zeroing in on the right organic compound to attack another RNA virus, Zika. In the January issue of Columns, Author Bonnie Rochman explores Dr. Gale’s story, including his personal childhood experience with virus in Federal Way, Wash. and touching on his pioneering work developing one of the first nonhuman primate models for HIV/AIDS. The piece is titled: UW Medicine lab races to halt the spread of the Zika virus.


Video courtesy of UW Medicine Strategic Marketing & Communications
 

Cliff Astley: 40 Years with the Washington National Primate Research Center

Cliff Astley celebrates 40 years of service this week with the University of Washington and Primate Center. Those years only count his employment. He actually started with the WaNPRC four years earlier in 1972 as a graduate student. He was interested in studying marine mammalian physiology and learned that Orville Smith, then director of the Primate Center, had previously studied the cardiovascular diving reflexes in elephant seals. He applied to UW and was initially an alternate, but ultimately was accepted to the Physiology and Biophysics program.

Cliff Astley
Cliff Astley is a staff surgeon with the WaNPRC.

After learning that there wasn’t much marine mammal work being conducted, he turned his attention to Rhesus monkeys for his thesis on the “Role of the Cerebellar Fastigial Nucleus on the baroreflex and cardiovascular responses to body tilting.” After graduating, he accepted a job with Orville Smith as a research scientist, managing Smith’s lab. Cliff’s first 25 years were spent in this research role for Smith with a broad range of duties, including: training animals, managing budgets, human resources, histology, IT and surgery. As Dr. Smith was retiring, they transitioned Cliff’s responsibilities from serving just the lab to offering IT and surgery services to the entire Primate Center.

Cliff and Keith Vogel began working together in 1972-1973. Cliff performed his first surgery in 1968, and Keith in 1969. In 2019, they will have a combined 100 years of surgical experience between them. It is hard for Cliff to imagine a surgical team with more experience anywhere in the world, especially a research surgical team.

“We have done hundreds and hundreds of procedures together,” says Cliff Astley of his relationship with Keith. “To me, our style, experience and skill levels are so similar that it is like working with 4 of my own hands. Hope he feels that way.” They both step in automatically to assist the other if they hesitate during a procedure.

Cliff and Keith spend more and more time training others in the surgical suite in anticipation of retiring in the future. Training and serving others is just part of what drives Cliff each day in his roles as IT consultant and staff surgeon.

Cliff Astley begins his 40th year of employment with the UW and WaNPRC on Tuesday, September 13.

Buffalo Lab Shares Research at Pacific Science Center Exhibit “Memory: Past Meets Present”

Buffalo Lab participates in exhibit at Pacific Science CenterImportant neuroscience research being conducted by the Buffalo Lab at the Washington National Primate Research Center is being shared at the Pacific Science Center.

The “Memory: Past Meets Present” exhibit is part of the Portal to Current Research that showcases local scientific research and its impact. The exhibit is open now through March 5, 2017.

“We are excited to be a part of this exhibit,” says Dr. Beth Buffalo, Chief Investigator with the Division of Neuroscience at the Washington National Primate Research Center. “This is a great opportunity to teach the public about our efforts to detect early warning signs of Alzheimer’s disease in healthy human patients.”

The Buffalo lab uses nonhuman primate research to track the combination of eye movements and the firing of neurons in the hippocampus to predict memory performance. In the lab, monkeys play a video game that has special software to track eye movement as the monkey navigates a virtual world in search of bananas. When the monkey finds a banana, the system provides a treat to the research subject. Treats are normally a special recipe of various fruit sauces. A map of the virtual world correlates to specific neurons in the patient’s hippocampus region of the brain.

The exhibit allows visitors to learn about this virtual built-in GPS system that human and nonhuman primates share. While playing the game, you’ll discover what information is stored in our brains while foraging for food in a virtual forest.

Buffalo Lab graduate student, Seth Konig, will give a public lecture titled “The Neuroscience of Memory: Why We Forget Some Things but Remember Others” at the Pacific Science Center on November 1 at 7 p.m. Admission is $5.

Visit www.pacificsciencecenter.org/lectures for more information.

This exhibit series is funded by a grant from the Paul G. Allen Family Foundation. Learn more by visiting www.pacificsciencecenter.org.

O’Connor Receives Post-Doc Fellowship, Will Conduct HIV/AIDS Research at Washington National Primate Research Center

Megan O'Connor, PhD, receives training fellowhship
Photo courtesy of John Gilbert, Geisel School of Medicine at Dartmouth.

Megan O’Connor, PhD., of the Fuller laboratory receives NIH-sponsored post-doctoral training fellowship from the University of Washington Center for AIDS and STD. The fellowship will pay O’Connor a yearly stipend to complete her post-doctoral research that will take place at the Washington National Primate Research Center.

The fellowship will assist O’Connor’s research by covering her salary and making funds available for her experiments. In addition, the fellowship program provides O’Connor with educational and networking opportunities designed to improve her knowledge of sexually transmitted diseases and AIDS research while enhancing her personal development as a post-doctoral fellow.

O’Connor joined the Fuller lab in January of 2016. The lab investigates therapeutic and prophylactic DNA vaccines for HIV. They are also testing new adjuvants designed to stimulate both systemic and mucosal antibody and T cell responses.

“Our lab has a major focus on investigating and improving therapeutic HIV vaccines using the simian immunodeficiency virus (SIV) macaque model for AIDS,” says O’Connor. “This research will help us to better understand how we can improve vaccine efficacy.”

HIV in humans is very similar to SIV, which is found in many species of nonhuman primates. The Fuller lab currently has several ongoing macaque model vaccine studies, of which O’Connor is involved in, which are planned to run through 2021.

HIV and SIV infection creates a misbalance of two cell types in the gut during infection. The misbalance of T-regulatory (Treg) and T helper 17 (Th17) cells is associated with HIV/SIV progression. The goal of O’Connor’s project is to determine whether SIV vaccination also has an effect on these different cell types in the gut mucosa.

Using the SIV macaque model for AIDS, they investigate the ability of vaccines to therapeutically treat SIV infection and residual virus in the gut mucosa. Previous studies in the Fuller lab showed that therapeutic immunization with a DNA vaccine that induces responses in the gut mucosa resulted in a functional cure from AIDS, or durable control of viral replication when administered to chronically infected animals in combination with short-term treatment with antiretroviral drugs (immunotherapy). These studies also aim to define the role of mucosal responses, in particular, and other immune mechanisms underlying the response to vaccination, protection from infection, or induction of durable viral control.

According to the World Health Organization, 37 million people are living with HIV globally. Since the beginning of the epidemic, more than 70 million people have been infected by the disease and 35 million have died from it. There are currently 17 million people worldwide on antiretroviral therapies for HIV/AIDS. The most promising vaccine approaches from these studies may lead to future clinical testing of these strategies in HIV infected humans.

Learn more about the AIDS-related disease research being conducted at the WaNPRC.

Learn more about the STD/AIDS Research Training Fellowship Program from the UW Center for AIDS and STD.

Nine Science Advocacy Groups Release White Paper on the Critical Role of Nonhuman Primates (NHPs) in Scientific and Medical Research

Paper highlights the essential role nonhuman primates play in finding treatments for serious and life-altering conditions such as Alzheimer’s disease, cancer, Zika virus, HIV/AIDS and Parkinson’s disease

Infographic depicting importance of nonhuman primate models of biological research.WASHINGTON — The Foundation for Biomedical Research (FBR) announced today the release of the white paper, The Critical Role of Nonhuman Primates in Medical Research. The white paper is a collaboration between FBR and eight premier scientific groups. The white paper highlights the essential role NHPs historically have and continue to play in finding treatments for serious and life-altering conditions such as Alzheimer’s disease, cancer, Zika virus, HIV/AIDS and Parkinson’s disease.

Collaborative scientific groups include: the American Academy of Neurology, the American College of Neuropsychopharmacology, the American Physiological Society, the American Society for Microbiology, the American Transplant Foundation, the Endocrine Society, the Federation of American Societies for Experimental Biology and the Society for Neuroscience.

“95 percent of the lab animals in scientific and medical research are rats and mice. Just half of one percent of research is conducted with nonhuman primates. That’s a tiny number. But their impact on our health is enormous,” said FBR president Frankie Trull. “NHPs, mostly monkeys, are the link between smaller animals and people. Once a disease or drug is understood in smaller species – like rats, mice, birds, zebrafish and worms – it is often then studied in monkeys.”

“Monkeys have certain traits and characteristics that make them essential and irreplaceable in medical research. They’re the bridge to the clinic,” said Dr. Jeffrey Kordower, a neuroscientist who examines how diseases like Parkinson’s and Alzheimer’s affect the brain.

Nonhuman primates (NHPs) are so similar to people genetically (up to 98 percent) that they show, unlike any other animal, how diseases work in the human body.Monkeys are more predictive than smaller species as to how a disease acts or how a treatment will work in people. Primate research has led to medical devices, treatments, advancements and cures that have saved and improved millions of lives. Research with NHPs has contributed to the following discoveries: polio vaccine, insulin for diabetes, coronary bypass surgery, hip replacements, kidney dialysis and transplants, organ transplants, organ rejection medications, medications for psychiatric illnesses, blood transfusions, chemotherapy, hepatitis B vaccine, HIV/AIDS medications, child lung transplants for cystic fibrosis, anthrax treatments, Parkinson’s disease treatments, and prostrate cancer treatments. To learn more about how research with NHPs is contributing to lifesaving cures for people, please download the white paper, The Critical Role of Nonhuman Primates in Medical Research or visit fbresearch.org.

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The Washington National Primate Research Center (WaNPRC) performs critical biomedical research leading to new advances in science and medicine. WaNPRC researchers are working to develop effective vaccines and therapies for HIV/AIDS and other infectious diseases as well as new advances in genetics, neuroscience, vision, and stem cell biology and therapy.  The WaNPRC directly supports the National Institutes of Health’s mission to translate scientific advances into meaningful improvement in healthcare and medicine. Learn more at www.wanprc.org.

 

Randy Kyes Leads 100th Field Course, Reflects on A Program Nearly 30 Years in the Making

Dr. Randy Kyes conducts field course while operating a drone in Thailand.
Dr. Randy Kyes operates a drone while conducting outreach program in Thailand.

Dr. Kyes often travels for up to seven months each year as the leader of the Division of Global Programs for the Washington National Primate Research Center and Director of UW’s Center for Global Field Study. Students from around the world get to learn about the convergence of environmental and global health through field course programs in countries such as: Indonesia, Nepal, China, India and Thailand. Kyes has spent nearly 30 years leading field courses in a dozen countries. UW Today writer Deborah Bach recently interviewed Dr. Kyes about his experiences, outreach efforts, challenges and rewards of running this successful program. The piece is titled: From crop-raiding monkeys to political unrest: UW’s Randy Kyes embarks on 100th field course.

Gaming the Memory System in the Buffalo Lab

Dr. Beth Buffalo from the Washington National Primate Research Center is trying to figure out how the primate brain forms memories.
Video games are used in the Buffalo lab to figure out how the primate brain forms memories.

Researchers are studying memory formation in the primate brain—and finding clues for interventions for Alzheimer disease along the way.

Giuseppe sits in a small room playing a videogame, joystick in hand. He zooms through a grassy field, foraging for big yellow bananas. Banking left, he speeds along a stonewall and captures two. A sweet treat rolls down a tube into his mouth, and he munches on his reward. Giuseppe, a monkey, is a research participant in the Buffalo Lab at the University of Washington.

In the lab next door, researchers watch a thin yellow line zigzag across a computer screen, with a loud crackling sound. “That’s the sound of a neuron firing an action potential,” says graduate student Seth Koenig, who is recording the activity of single neurons in the monkey’s brain, via a hair-thin electrode implanted into the medial temporal lobe. A camera setup tracks his darting eye movements.

Along with four other monkeys trained to play various computer games, Giuseppe is helping researchers to figure out how the primate brain forms memories—and clues to interventions for the memory impairments of Alzheimer disease along the way.

Read full article from the UW Medicine Memory & Brain Wellness Center…

What Women Need to Know About the Zika Virus

Map of potential Zika virus outbreak.According to the Centers for Disease Control and Prevention, the Zika virus is spread to people primarily through the bite of an infected Aedes mosquito. Common symptoms for adults is very similar to a flu virus, including: fever, rash, joint pain, and dry and itchy eyes. Zika virus can be passed from a pregnant woman to her fetus. Infection during pregnancy can cause Microcephaly and other severe brain injuries.

The virus continues to spread. Women who are pregnant or planning to become pregnant should not travel to affected areas in South America, Central America and the Caribbean. Kristina Adams Waldorf, UW associate professor of obstetrics & gynecology and affiliate researcher at the Washington National Primate Research Center, is studying this viral disease. She was recently interviewed by KOMO news and offers advice to pregnant women on current recomendations on travel and provides basic Zika virus information. Click here to read the full article.

No Evidence of Autism-Like Behavior after Vaccination of Infants

Infant Rhesus Macaques Show Normal Development after Receiving Pediatric Vaccines

SEATTLE – Correlation of childhood vaccines and autism studied at the Washington National Primate Research Center (WaNPRC). Study shows no evidence of autism-like behavior or neuropathology in rhesus macaques after receiving typical childhood vaccinations. All animals in the study developed normally after being administered thimerosal-containing vaccines.

infant pigtail macaque
Infant Pigtail macaque (Macaca nemestrina) nurses from mother at Washington National Primate Research Center.

The data indicate that administration of thimerosal-containing vaccines such as Hepatitis B and DTap, to rhesus macaques does not result in brain or behavior abnormalities like those observed in autism spectrum disorder. The study results are published in the journal Proceedings of the National Academy of Sciences.

“It is of great importance to determine whether childhood vaccines that contain this preservative play a significant role in altering brain development, such as autism,” says lead investigator Laura Hewitson of The Johnson Center for Child Health and Development in Austin, Texas, and affiliate investigator with the WaNPRC.

The study provides a comprehensive analysis of the influence of thimerosal-containing vaccines on the brain and behavior in a nonhuman primate model. Virtually no negative behaviors, such as rocking, self-clasping, and repetitive behaviors were reported, regardless of vaccination status. No cell or protein changes in the cerebellum, hippocampus or amygdala were found between vaccinated and unvaccinated animals in the study.

The perceived safety of childhood vaccines has had a major impact on immunization rates – including the measles mumps and rubella (MMR) vaccine. Concerns emerged during the 1990s about thimerosal’s potential to harm children’s brain development.

Thimerosal is a mercury-containing compound. For decades it was employed to keep vaccines free from contamination by germs and bacteria. In 2001, The Food and Drug Administration recommended that manufacturers remove thimerosal or reduce it to trace amounts in pediatric vaccines. It is still used as a preservative in flu and meningitis vaccines. The FDA determined that children receiving multiple thimerosal-containing vaccines at a young age were at risk for exceeding the Environmental Protection Agency’s safe exposure limits for methylmercury.

The study was conducted at the Washington National Primate Research Center with pregnant female rhesus macaques provided by the California National Primate Research Center

The WaNPRC performs critical biomedical research leading to new advances in science and medicine. WaNPRC researchers are working to develop effective vaccines and therapies for HIV/AIDS and other infectious diseases as well as new advances in genetics, neuroscience, vision, and stem cell biology and therapy. The WaNPRC directly supports the National Institutes of Health’s mission to translate scientific advances into meaningful improvement in healthcare and medicine. Learn more at www.wanprc.org.