NHP Research Models
Humans and nonhuman primates have a high degree of biological similarity, providing researchers with incomparable opportunities to study human diseases and disorders. The animal models living within our colony are a unique resource for translational research that can have an incredible impact on human health. All our animals have extensive veterinary records and have participated in a BioBehavioral Assessment (BBA) that established baseline evaluation of behavior and physiology at six months of age. We have been performing these assessments for decades and, in most cases, know an animal’s pedigree nine generations deep.
Specific Pathogen-Free Primates
Since 1987, the CNPRC has been establishing specific pathogen-free (SPF) monkey colonies with additional support from the National Institutes of Health. The goal of this breeding program is to improve both the overall nonhuman primate colony health and the quality of science conducted by eliminating persistent viral infections representing potential confounding variables. The CNPRC SPF colony also increases personnel safety for animal care staff by reducing health risks associated with potential exposure to nonhuman primate pathogens.
Research Models for Aging
The CNPRC has maintained a colony of aged rhesus macaques for over 35 years. The majority of this colony is composed of retired breeders who are research-naive. As part of the breeding colony, this population has pedigree data determined by genetic analysis going back nine generations. This unique research resource is an essential component of the CNPRC focus on lifespan research starting with the fetus in gestation to the geriatric adult. Research programs using the aged rhesus population range across all four of the CNPRC research units and include studies in:
- Cognitive aging
- Alzheimer's Disease
- Immune senescence
- Ophthalmology and age-related retinal disorders
- Respiratory biology and age-related respiratory disorders
- Geriatric biobehavioral assessment
- Metabolic Syndrome and Type 2 Diabetes
- COVID-19 and aging
Research Models for Neurodevelopment
The CNPRC’s large colony of domestically bred rhesus macaques includes a breeding colony of socially housed monkeys and a timed-mating program. These unique resources provide an invaluable tool to study complex human neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. It has also enhanced the study of certain infectious diseases, like Zika, that affect developmental neuropathology. Assessments of social and cognitive development designed to maximize translational potential are used to evaluate the validity of our nonhuman primate models. Examples of developmental testing batteries include:
- Developmental milestones and biobehavioral assessments
- Qualification of social development in rearing groups
- Quantification of mother-infant interactions
- Quantification of peer social interactions
- Processing of social stimuli using eye-tracking technology
This rigorous behavioral assessment is just one of the many ways the CNPRC seeks to maximize the translational power of our nonhuman primate models for neurodevelopment. These assessments are enhanced by an established battery of biomarkers used to directly compare primate models with human diseases. High-powered qualitative microscopic approaches are also used to characterize developmental neuropathology.
Research Models for Neurobiology
The CNPRC’s large geriatric population provides an opportunity to study cognitive function in an older population. Just as cognitive decline is frequently a feature of human aging, aged rhesus macaques demonstrate robust changes in cognition and memory that can be evaluated pre and post-drug treatment. Our greatest example of this is a model for Alzheimer’s Disease Pathology. Aged animals are tested by research staff with decades of experience in behavioral testing, including:
- Delayed non-matching to sample
- Delayed response
- Affective behavior
In addition to rigorous behavioral assessment, the CNPRC has established a battery of biomarkers that can be used to assess physiological endpoints in therapeutic trials. These biomarkers, combined with behavioral measures, can identify treatment effects associated with novel compounds.
Research Models for Psychological Disorders
Mood disorders constitute major threats to well-being in all human populations and are often seen in conjunction with the experience of stressors such as interpersonal conflict, economic hardship, and social loss and isolation (e.g., loneliness). The CNPRC’s unique BioBehavioral Assessment (BBA) program, an assessment performed in infancy for a variety of biobehavioral measures, helps scientists identify naturally occurring psychological disorders within the colony as well as those who are most at risk for developing certain behaviors in adulthood. Through regular behavioral testing and analysis of biomarkers, CNPRC scientists can study psychological disorders and their causes, triggers, effects, and treatments. Examples of Nonhuman Primate Models for Psychological Disorders include:
- Anxiety
- Depression
- Schizophrenia
- Loneliness
- Social Stress
Research Models for Respiratory Biology and Disease
The CNPRC has been a leader in understanding nonhuman primate lung biology and respiratory disease for more than 30 years. It has the distinction of being the only NIH-supported National Primate Research Center with a Respiratory Diseases research unit and scientific expertise in airway immunity, environmental air pollutants, lung physiology, and asthma. A full suite of physiological endpoints is available to assess inhalational safety, therapeutic efficacy, and disease development longitudinally. We also have advanced inhalation exposure capabilities, including a range of aerosol administration modalities. Our facility supports both nonhuman primate and rodent models of respiratory disease. Examples of Nonhuman Primate Models for Respiratory Biology and Disease include:
- Non-Atopic Asthma
- Adult and childhood asthma (Th2 high and Th2 low asthma phenotypes)
- Tobacco and e-cigarette exposures/COPD
- H1N1 influenza infection
- Pulmonary fibrosis
- Wildfire smoke health outcomes
Research Models for Infectious Disease
The CNPRC’s large colony of domestically bred rhesus macaques allows us to study infectious diseases across the complete lifespan, from gestation to geriatric. Preclinical research performed in nonhuman primates provides the crucial proof of concept and scientific foundation to test new strategies in human clinical trials. This is extremely important in the study of pharmacology and therapeutics during pregnancy, infancy, and throughout childhood. Basic and translational research in infectious diseases is integrated and synergistic with other research areas (including immunology, pharmacology, pathology, biology, and neuroscience) at the CNPRC, the UC Davis School of Medicine, the UC Davis School of Veterinary Medicine, and other institutions. The CNPRC has a proven track record of R&D partnerships with biotech and pharmaceutical companies to help move novel products through the pipeline of drug development toward clinical trials and approval. These preclinical studies can be performed under GLP protocols. Some studies do not involve the actual infectious agents; examples are experiments on the immunogenicity and safety of novel vaccines, or the pharmacokinetics and safety of antiviral drugs. Infectious diseases that were recently or are currently being studied include:
- HIV/AIDS
- Cytomegalovirus (CMV)
- Influenza
- Influenza
- SARS-CoV-2
- Zika virus
- Dengue virus
- Mayaro virus
- Chikungunya virus
- Entamoeba histolytica
- Rift Valley Fever
Research Models for Psychological Disorders
Mood disorders constitute major threats to well-being in all human populations and are often seen in conjunction with the experience of stressors such as interpersonal conflict, economic hardship, and social loss and isolation (e.g., loneliness). The CNPRC’s unique BioBehavioral Assessment (BBA) program, an assessment performed in infancy for a variety of biobehavioral measures, helps scientists identify naturally occurring psychological disorders within the colony as well as those who are most at risk for developing certain behaviors in adulthood. Through regular behavioral testing and analysis of biomarkers, CNPRC scientists can study psychological disorders and their causes, triggers, effects, and treatments. Examples of Nonhuman Primate Models for Psychological Disorders include:
- Anxiety
- Depression
- Schizophrenia
- Loneliness
- Social Stress
Research Models focused on Reproduction, Development, Pregnancy, and Gene Therapy/Somatic Cell Gene Editing
Nonhuman primates and humans share many reproductive and developmental features that emphasize their importance as translational models. The unique expertise of CNPRC Core Scientists provides collaborative opportunities to address research questions associated with all developmental stages (embryo, fetus, newborn, infant), juveniles, young adults, premenopausal/transitional reproductive stages, and advanced geriatrics.
Included are studies that focus on early (prenatal) onset of disease and new therapeutic interventions, regenerative medicine and gene therapy/somatic cell genome editing; lifespan health – from the earliest developmental stages to aging populations; in vivo imaging technologies for precision medicine; and preclinical IND-enabling studies for clinical translation.
Examples of ongoing studies include:
- Viral teratogens and virus trafficking during pregnancy
- Maternal/placental/fetal interactions and microchimerism
- Immune and hematopoietic ontogeny
- Stem cell transplantation and tissue engineering
- Gene Therapy and Somatic Cell Genome Editing (in utero to postnatal)