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WaNPRC’s Orsborn Adds NSF CAREER Award to Study Neural Interfaces

Photo of Amy Orsborn with her titles: Clare Boothe Luce Assistant ProfessorElectrical & Computer Engineering & Bioengineering on a gradient background that is purple and goldAmy Orsborn, Neuro core scientist at WaNPRC and Clare Boothe Luce Assistant Professor in Electrical & Computer Engineering and Bioengineering at the UW, was recently named a recipient of the prestigious National Science Foundation (NSF) CAREER award. The award will support Orsborn’s research investigating how the brain and nervous system respond to using sensorimotor neural interfaces, which show promise for treating a wide range of neurological conditions, such as paralysis caused by spinal cord injury or stroke.

Orsborn’s work will help to lay a foundation for creating advanced computer algorithms in sensorimotor neural interfaces that can better adapt to the user. A fundamental challenge inspires her research in neural engineering, where neural interfaces engage with the brain and nervous system in what is called a “closed loop” in which the user and the device influence each other. This closed loop has enormous therapeutic potential. Her aoLab will conduct experiments using two different types of neural interfaces: muscle/nervous system interfaces applied to humans on the surface of the skin, and brain-computer interfaces applied to the sensorimotor cortex of non-human primates. Comparing the results could help the team understand how the brain performs computations and how closed-loop devices influence them.

The NSF selects award recipients who are faculty members at the beginning of their careers to lead advances in the mission of their department or organization. The NSF CAREER program intends to provide stable support, enabling awardees to develop not only as outstanding researchers but also as educators demonstrating commitment to teaching, learning and dissemination of knowledge.

Orsborn has been racking up accolades. She recently received the Ronald S. Howell Distinguished Faculty Fellowship. The Electrical & Computer Engineering department has more on the story.

Exciting Collaborations

Ongoing studies with Umoja Biopharma, HDT Bio, and the Allen Institute

Nonhuman primate studies are crucial in biomedical research, particularly developing new therapies. The pigtail macaque monkeys at the Washington National Primate Research Center share a closer genetic and physiological resemblance to humans than other animal models. This similarity allows researchers to predict better how a therapy might behave in humans, offering valuable insights into potential efficacy and safety.

Such is the case with Umoja Biopharma’s VivoVec platform for chimeric antigen receptor T (CAR-T) cell therapy. In this in vivo study, the researchers observed the activation and expansion of CAR-T cells in the monkeys and their impact on target cells. The researchers, supported by the animal care and research staff at WaNPRC, compared the CAR-T cell expansion and persistence in monkeys with data from previous studies on ex vivo CAR-T therapies in similar primate models. This provided valuable insights into the platform’s potential advantages.

Overall, this public/private partnership is a critical bridge between preclinical research and clinical translation, providing essential data on the safety, efficacy, and feasibility of new therapies like Umoja’s VivoVec platform for CAR-T cell therapy.

A separate project led by HDT Bio Formulations Director, Dr. Amit Khandar, aims to assess the effectiveness of their LION™ delivery technology and self-replicating RNA (repRNA) vaccine platform against HIV-1. The focus is on inducing broadly neutralizing antibodies (bNAbs), crucial for targeting the heavily masked envelope glycoprotein of the virus. In the R33 phase, the collaboration with UW’s Fuller Laboratory and the WaNPRC will evaluate immunogenicity and efficacy in nonhuman primates (NHPs), pivotal steps before potential clinical trials. This phase will provide essential data on protection against a SHIV challenge and guide decisions regarding human trials. Safety assessments, especially concerning mRNA-based vaccines, are emphasized, drawing from mouse models and NHPs to address concerns ensuring confidence in the vaccine’s safety profile. The ultimate goal is to advance toward clinical trials, leveraging promising results from NHP studies to inform future steps in vaccine development.

“Ultimately, it might be that a combination of nucleic acid platforms will be needed to achieve the “holy grail” that is efficacy in humans. The combination of safety, immunogenicity, and efficacy in nonhuman primates will support the decision to enter clinical trials. If the data is promising, we have the manufacturing infrastructure to work with existing HIV clinical trial networks and enter phase I evaluation. – Dr. Amit Khandhar, HDT Bio

Scientists at the Allen Institute celebrate their global collaboration in mapping the hundreds of billions of cells in rodents, macaque monkeys, and human brains.  They are mapping them by their type and function as part of the BRAIN Initiative® Cell Atlas Network, or BICAN, with financial support from NIH’s B.R.A.I.N. Initiative, or Brain Research Through Advancing Innovative Neurotechnologies® Initiative.

The WaNPRC, by providing the Allen Institute’s NHP models, is helping to bridge the knowledge gap between rodent models and humans.

“The Allen Institute has made amazing progress characterizing the cell types that compose the mouse brain and connections among them. Extending these efforts to primates is a critical next step on the way to clinical application. This is being achieved via the symbiotic relationship they have with the WaNPRC.” – Dr. Gregory Horwitz, WaNPRC Neuroscience unit chief

This brain atlas lays the groundwork for mapping the entire mammalian brain and enhancing comprehension of puzzling brain disorders, such as those affecting the neurons responsible for motor function, like amyotrophic lateral sclerosis (ALS).

Highlights from the Himalayas

Dr. Randy Kyes, chief of the Global Conservation, Education & Outreach unit at the WaNPRC, and his Nepali colleagues wrapped up their 21st year of field training in Kathmandu, Nepal, before gaining some altitude in their annual climb up to their field sites in Langtang National Park. This was a return the site of a devastating  7.8 magnitude earthquake and resulting landslide in April of 2015.

Kyes and his Nepali colleagues highlighted their dedication and collaboration over the past two decades in a two-day photo exhibit titled “Langtang Through the Lens of Field Researchers.” The event was hosted at the Central Library of Tribhuvan University (TU) and sponsored jointly by the library itself, and the university’s Department of Library and Information Science, along with the Central Department of Zoology.

In the foreground are three small Nepali children sitting on a small horse led by an older man wearing a backpack while in the background is the sparse, rocky terrain of the Himalayan foothills in this promotional poster for the photo exhibition, Lantang Through the Lens of Field Researchers.

The exhibition provided a visual journey into the heart of the Himalayas and served as a celebration of over two decades of partnership and collaborative research, training, and outreach in the Langtang region.

At the heart of this celebration were the tireless efforts of dedicated field researchers, including long-time collaborators like Prof. Mukesh Chalise and past students turned colleagues, Dr. Narayan Koju and Dr. Laxman Khanal. In a moving speech at the opening of the event, Kyes also expressed his gratitude to the local residents of Langtang for their years of support noting that this exhibition is dedicated to their dear friends who were lost in the terrible 2015 earthquake and landslide.

Supported in part by OEI, USA, the exhibition not only showcased the beauty of Langtang, but also underscored the importance of these photographs as valuable sources of information for future research endeavors. It served as a reminder of the enduring impact of collaborative efforts in preserving and understanding our natural world.

Collaborating faculty wearing Nepalese khata ceremonial scarves, from left to right: Professor Laxman Khanal, Professor Mukesh Chalise, Professor Randy Kyes, Assistant Professor Narayan Koju
L to R: Associate Professor Laxman Khanal and Professor Mukesh Chalise (Tribhuvan University), Professor Randy Kyes (University of Washington), Assistant Professor Narayan Koju (Nepal Engineering College, Pokhara University)

This collaboration started in 2000 when I first visited Nepal and met with Mukesh Chalise, who became my long-time colleague. Two of our past field course students now colleagues, Laxman Khanal and Narayan Koju, are continuing this long collaboration – leading the way into the future.

Randall C. Kyes, PhDGlobal Conservation, Education & Outreach unit chief

 

Updates from the Field: Southeast Asia

Friday, February 2, 2024:

Midway through a thrilling three-week macaque distribution survey in Sumatra, spearheaded by Dr. Entang Iskandar from the Primate Research Center (PSSP) at IPB Bogor University, Randy’s journey took an exciting turn. Navigating through the verdant landscapes of the Aceh province, they stumbled upon two substantial groups of macaques, featuring both pig-tailed macaques (Mn) and long-tailed macaques (Mf), congregating along the roadside.

“It has been a pleasure to assist my long-time colleague Dr. Entang Iskandar (Project Leader) with this collaborative effort between PSSP-IPB and WaNPRC.” -Dr. Randy Kyes
A spectacle unfolded before them as they keenly observed instances of interspecific grooming and an unusual closeness between members of both species. The dynamic interaction between the macaque species provided valuable insights into their social behaviors, adding depth to the understanding of their intricate relationships. Photo: Randall C. Kyes

It is a real pleasure to be assisting my long-time colleague Dr. Entang Iskandar who is leading this important study.  I’ve worked closely with Entang and PSSP-IPB for over 30 consecutive years and I believe this project represents truly foundational work – helping to fill in the gaps regarding macaque distribution and target locations for in-depth population surveys.

Dr. Randy KyesGlobal Conservation, Education and Outreach unit chief

Saturday, January 27, 2024:

On the fifth day of their collaborative three-week distribution survey in Sumatra, Dr. Entang Iskandar and Randy continued north as they delved into the northern half of the island for Phase 2. Their expedition led them to Taman Kera, Sumatra Utara, where they encountered sizable Mn and Mf macaque groups.

Capturing a defining moment, Randy’s lens focused on an adult male pigtailed macaque. The collective efforts of experts from IPB’s Primate Research Center and WaNPRC’s Global Conservation and Educational Outreach (GCEO) unit continue to unravel the mysteries of macaque distribution and behavior, highlighting the importance of collaborative research in conservation. Photo: Randall C. Kyes

Wednesday, January 24, 2024:

Dr. Kyes expresses his pleasure at returning to Indonesia, once again joining forces with Dr. Entang Iskandar for the second phase of their macaque distribution survey. The collaborative spirit is resonating as they work towards unraveling the nuances of macaque populations of pig-tailed and long-tailed macaques in Sumatra.

Long-tailed macaque sits in tree
A highlight of their venture is an encounter with an adult male long-tailed macaque, captured in a moment of grace. The collective efforts and camaraderie between research partners contribute significantly to their shared goal of understanding and conserving the biodiversity of Sumatra. Photo: Randall C. Kyes

Monday, December 25, 2023:

Baby rhesus monkey on tree branch
As the curtain falls on the 2023 field season at Wat Phrabuddhabat Pa Reau in Chiang Rai, Thailand, a heartwarming scene unfolds – an infant rhesus macaque preparing for a daring leap. This memorable moment serves as a fitting conclusion to a season of discoveries and underscores our commitment to exploring human-primate conflict and coexistence. Photo: Randall C. Kyes

Looking forward to 2024, Randy and research scientist Dr. Pensri (“Elle”) Kyes, along with partners at Mahasarakham University and Mae Fah Luang University promise to delve deeper into the intricate dynamics of the relationship between humans and wild monkeys. The journey continues, and their shared dedication to bridging the gap between humans and primates propels them into the new year with enthusiasm and determination.

Fact Sheet: The Crucial Role of Pig-Tailed Macaque Monkeys in Health Discovery and Disease Treatment

Key Details: Pig-Tailed Macaque Monkeys


Species:
Macaca nemestrina

Other common names: southern pigtail macaque, Sundaland pig-tailed macaque or Sunda pig-tailed macaque.

Geographic locations of wild populations: Indonesia, Malaysia, Thailand.

Import status: All pigtails at the Washington National Primate Research Center are purpose-bred for research.

Conditions negatively impacting wild pig-tailed macaque populations: Human encroachment into natural habitats, climate change, pollution, oil and gas production, human recreational activities, hunting and trapping.

Source of pig-tailed macaques studied at the University of Washington: All pig-tailed macaque monkeys involved in research at the University of Washington were bred expressly for involvement in health research.

Diseases and Disorders That Require the Study of Pig-Tailed Macaque Monkeys

  • Women’s Health – Like humans, pig-tailed macaques experience menopause, menstrual cycles and give birth throughout the entire calendar year. We also share similar reproductive anatomy making these animals an important model to combat illnesses, such as chlamydia, that impact women around the globe.
  • Health Issues Associated with Premature Birth – Research in pig-tailed macaques helps researchers understand and counteract premature birth and neonatal hypoxia. Neonatal hypoxia, the tragic result of oxygen deprivation shortly before or after birth, affects roughly 2-3 out of 1,000 live human births in the U.S. each year.
  • Zika Virus Research – The study of Zika virus transmission during pregnancy occurs in pig-tailed macaques because their immune system is similar to humans.
  • HIV/AIDS Research – HIV, the virus that causes AIDS, impacts the brains of both humans and pig-tailed macaques in a similar way. People with HIV are living longer, healthier lives thanks to past research in pig-tailed macaques.
  • Valley Fever Research – Like humans, pig-tailed macaques are uniquely susceptible to Valley fever, a disease caused by inhaling a soil-dwelling fungus. This means these animals play a crucial role in the fight against Valley Fever, a growing health threat exacerbated by increasing global temperatures.
  • Aging and Social Behavior Research – There is growing evidence that pig-tailed macaques are a highly valuable research model for the study of aging and certain social behaviors where animal/human parallels exist.

Generated in collaboration with Americans for Medical Progress 

Orsborn Awarded the Washington Research Foundation’s Ronald S. Howell Distinguished Faculty Fellowship

Already holding the esteemed title of Clare Boothe Luce Assistant Professor of Electrical & Computer Engineering, Dr. Amy Orsborn, Neuro core scientist at WaNPRC, was among three University of Washington (UW) faculty selected to comprise this inaugural cohort by the Washington Research Foundation (WRF). The UW Department of Electrical & Computer Engineering describes the fellowships as, “…honoring those who have research emphasis in neuroscience fields, a record of demonstrating Diversity, Equity and Inclusion (DEI) initiatives, and the capacity to bridge disciplines and domains.”

Amy’s work is groundbreaking, merging her computational expertise with innovative approaches in experimental systems neuroscience. The result? Fresh, fundamental insights into how neural circuits master the art of learning. Her mission? To shed light on the intricate mechanisms behind learning within expansive brain networks, all with the ultimate aim of enhancing our ability to manipulate cortical dynamics for treating neural injuries and disorders. Learn more about the Fellowship and the other recipients, Drs. Gabe Cler and Sam Golden, within the Office of Research’s announcement, “Three Faculty Chosen for the Washington Research Foundation Ronald S. Howell Distinguished Faculty Fellowship.”

A big thanks to the Washington Research Foundation @wrfseattle for their support! It’s a huge honor to receive an award focused on things I value so much: interdisciplinary research & teaching/outreach to make science a more inclusive and equitable place.

Amy Orsborn, PhD@neuroamyo

Beyond her research and teaching, Amy is deeply involved in the Women in Science and Engineering program. She’s also the co-founder of the Women in Neural Engineering group, dedicated to advancing the careers of women in the field. Her commitment to diversity and equity in science and engineering is crystal clear.

Dr. Michael Gale, Jr. awarded $8.5M P01 Grant for HIV Vaccine Research

The goal of this project is to define the molecular and cellular mechanisms by which IL-15 programs protective immunity with the RhCMV-SIV vaccine to inform our understanding of HCMV-HIV vaccine immunity against HIV.

The world is in need of an effective HIV/AIDS vaccine, and the cytomegalovirus (CMV) vector-based HIV/SIV vaccine featured in our studies is highly efficacious and durable to uniquely mediate viral “replication arrest” efficacy in the Rhesus Macaque-SIV model. Vaccine immunity is mediated by unconventional MHC-E-restricted CD8+ T cell responses and induction of IL-15, which correlate with vaccine protection. The work proposed in this application will reveal the molecular mechanisms of immune programming by the CMV-based vaccine and IL- 15 actions to inform human testing of this vaccine concept in ongoing and future phase I/II trials.

NIH P01 AI177688:     $8,472,008

 

WaNPRC AD for Research quoted in Scientific American on the pursuit of a Valley Fever vaccine

As seen in October 2023 issue:
The disease hits farmworkers and outdoor laborers disproportionately hard.

The article discusses the growing threat of Valley fever, a fungal disease caused by Coccidioides, in the western United States, particularly in the San Joaquin Valley of California. Valley fever thrives in dry, dusty environments and can be inhaled as airborne pathogens. It is characterized by symptoms such as coughing, fevers, body aches, fatigue, rashes, and appetite loss. The disease disproportionately affects vulnerable populations, including Latino, Asian, and Native American communities, due to their frequent exposure to dusty outdoor locations. Many of those affected lack access to basic healthcare and are afraid to seek medical help due to concerns about employer retaliation or deportation.

The article highlights that Valley fever is underreported, underdiagnosed, and underfunded, with limited research on the disease. Researchers are working to better understand its spread and develop treatments and vaccines. Climate change and environmental factors, such as increased dust exposure, are contributing to the spread of Valley fever, and there is concern that it could extend into new regions in the future.

One potential benefit of a Valley fever vaccine is that it could be a one-and-done kind of thing—unlike those for influenza or even tetanus, which must be updated regularly. According to studies by microbiologist Deborah Fuller of the University of Washington School of Medicine, people who get Valley fever develop lifelong immunity. That, Fuller says, “is the golden egg.”

Dr. Deborah FullerAssociate Director for Research, Core Scientist

Fuller’s research team is actively working on developing both DNA and RNA-based vaccines. These vaccines are designed to stimulate the body to produce specific proteins that can trigger a strong immune response. What makes these vaccines particularly valuable is that they have the potential to do more than just combat Valley fever. They could also serve as a valuable tool for researchers to gain a better understanding of how the immune system responds to other fungal diseases. This research could ultimately lead to improved treatments for a range of fungal infections, providing valuable insights into the field of fungal disease immunology.

Efforts are also underway at both the local and federal levels to address the threat of Valley fever, with some researchers working on vaccines for humans, building on the success of a vaccine for dogs. Funding for Valley fever research has increased in response to rising incidence rates, but there is a long way to go in terms of awareness, diagnosis, and treatment of this fungal disease, especially among vulnerable populations like farmworkers.

Related:
https://news.nau.edu/valley-fever-collaborative/
https://pubmed.ncbi.nlm.nih.gov/37730871/

A community of neuroscientists stands together

As we face the prospect of living longer and developing age-related diseases including Alzheimer’s and other dementias, and long COVID, it is an especially critical time to be a neuroscientist. At the Simian Collective (SimCo) meeting in Chicago we heard exciting new findings from neuroscientists across the country who are unraveling the mysteries of the brain in health and in disorders including autism, stroke, schizophrenia, depression, Alzheimer’s and Parkinson’s disease. The stars of the meeting were the young investigators who are taking our knowledge to the next level by developing and implementing state of the art technologies and answering questions about the brain that many of us only dreamed about 15-20 years ago.

The meeting was also emotional for all of us all as we celebrated the lives, legacies, and scientific accomplishments of two of our esteemed colleagues – Drs. Sliman Bensmaia and Krishna Shenoy – two brilliant scientists whose work with both human and nonhuman primates alike, made a difference in the everyday lives of people struggling with movement disability from spinal cord injury and stroke. Sliman and Krishna were remarkable people; fun-loving, mischievous, and deeply committed husbands and fathers. We are all better people for knowing them.

Though not expected at a professional, scientific event, SimCo attendees experienced another set of emotions – terror and fear. During a keynote presentation from an internationally renowned neuroscientist, Dr. Betsy Murray, two people from PETA entered the room and one jumped on the stage carrying a sign and screaming horrible untruths about Dr. Murray and her work as he quickly and aggressively walked toward her. The other was taking a video of the scene while shouting “Do not touch me” throughout. It was scary – it was terrorism – and it is unacceptable. At least one of these disruptors was identified as engaging in similar terrorizing behavior against another one of our colleagues Dr. Agnes Lacreuse – notably also a woman.

This very frightening event that occurred at SimCo is not an isolated incident. It is part of a campaign of harassment and intimidation against scientists who are working hard every day to end suffering for all living beings. The animal enterprise terrorism act (AETA) passed into law in 2006, expressly forbids the kind of harassment and intimidation in which PETA engages. AETA needs enforcement and PETA actors need to be prosecuted.

Reflections from the Field: Joint Meeting of IPS and MPS 2023, Kuching, Sarawak, Malaysia

In a sobering talk presented at the joint conference of the International and Malaysian Primatological Societies in Kuching, Sarawak, Malaysia by Dr. Anna Holzner (from the University of Leipzig), the audience learned that the southern pig-tailed macaque monkey, the primate species that we breed at WaNPRC, is facing immediate and long-term threats in pigtail habitat countries such as peninsular Malaysia. According to Dr. Holzner, many of the forests are being converted to oil palm plantations. To adapt to these environmental changes, pigtails travel into the plantations and forage, putting them at increased risk of predation and exposure to pesticides. These immediate risks are compounded by the long-term impacts on lifespan resulting from changes in social structure and behavior that occur because of foraging in the plantations. (https://pubmed.ncbi.nlm.nih.gov/34993012/)

The Washington National Primate Research Center (WaNPRC) is deeply committed to capacity building and conservation of primates across the globe through the work of our Global Conservation Education and Outreach unit (GCEO) established in 1999. The International Union for Conservation of Nature recently upgraded the classification of the southern pig-tailed macaque to endangered based on the projected decline in population. Noting IUCN criteria specifically indicates, “Population reduction projected, inferred or suspected to be met in the future (up to a maximum of 100 years).”

WaNPRC’s GCEO, along with our partners at the Primate Research Center at IPB University (IPB) in Bogor, Indonesia are leading the effort to collect data on the distribution and population of southern pig-tailed macaque monkeys.  We at WaNPRC remain committed to this effort and will continue to work hard on behalf of these animals. We are hopeful that our collaborative efforts aimed at understanding the pig-tailed macaque in habitat countries combined with our deep knowledge of these animals from our years of experience breeding and caring for them, will help ensure these precious animals stay vital in their native habitats.