Interdisciplinary Research Groups
The ONPRC has established Interdisciplinary Research Groups in the areas of Biology of Aging, Early Childhood Health and Development, and Primate Genetics to analyze and plan interdisciplinary research, and to inform areas of future recruitment.
Biology of Aging
As human life expectancy continues to increase, there is a growing need for scientific knowledge about ways to promote healthy aging. The objective of the Biology of Aging Program is to enhance our understanding of the mechanisms that underlie normal and pathological human aging, and to help with the development of effective therapies for age-associated diseases.
Key studies conducted by investigators at ONPRC have demonstrated age-related changes in several physiological systems in the rhesus macaque, paralleling those reported in humans. For example, they have found that female macaques undergo menopause, and show associated perturbation of their circadian rhythms, as well as declines in their immune function and cognitive abilities. Furthermore, ongoing studies are yielding clinically relevant discoveries, that are helping physicians to: 1) evaluate the therapeutic efficacy of various hormones for cognitive and emotional health in postmenopausal women; 2) determine how diet modulates age-related decline in immune function, circadian physiology, learning and memory; and 3) enhance vaccine efficacy and reduce morbidity and mortality following infection by delaying the aging of the immune system.
Such multi-disciplinary approached are made possible because of the world-class scientists and clinicians who make up the aging research consortium at OHSU. In addition, the maintenance of an aging rhesus macaque colony at ONPRC represents a major valuable resource. Nonhuman primate models provide several distinct advantages over rodents and have the potential to disclose important inter-related mechanisms that underlie human aging. This strength fosters the advancement of the basic, translational, and clinical research that is required to for treatment of age associated diseases and for maintenance of life quality in the elderly.
The ONPRC Biology of Aging Program is an active component of the OHSU Healthy Aging Alliance.
EARLY CHILDHOOD HEALTH & DEVELOPMENT
The early childhood period is now being recognized as one of the most important developmental phases throughout one's lifespan. The intrauterine environment and gestational length and size at birth can have profound impact on an individual's development and mental and physical health throughout childhood as well as in adult life.
The focus of the Early Childhood Health & Development (ECHD) Program is to bring together a diverse expertise of scientists at ONPRC, OHSU and beyond and to utilize non-human primate (NHP) models which encompass key developmental stages known to strongly influence the risk of developing cardiovascular, pulmonary, metabolic and psychological disease during early childhood and throughout life. The ECHD Program investigators at ONPRC collectively study events that occur during pregnancy (i.e., intra-amniotic infection, hypoxia, growth restriction, maternal nutrition, placental abnormalities and preterm birth), as well as broad aspects of human development (i.e., cardio-pulmonary physiology, neurodevelopment, immune function and vaccine development) as a means of understanding factors and/or events during prenatal and postnatal life that can have profound effect on the overall health of an individual.
The ONPRC is internationally recognized for its translational research in pregnancy and reproductive sciences and is one of the few primate centers in the United States that has the infrastructure and technical expertise to sustain an outstanding rhesus macaque time-mated breeding program (TMB). The TMB program is integral component of the animal resources provided to investigators by the ONPRC, in particular the ECHD Program. Based upon their biological similarities to humans, NHPs are particularly useful for studies related to human paturition and developmental biology. Similarities include: a) physiology of the menstrual cycle and implantation, b) the structural features of the uterus and cervix, placenta and fetal membranes, c) the mechanism of labor and myometrial responses to prostaglandins and oxytocin and their inhibitors/antagonists, and d) the regulation of the feto-placental steroidogenesis is qualitatively similar in humans and NHPs.
The primary mission of the PGP is to describe the relationship between genetic or epigenetic variation and disease in NHPs, and to translate those findings to human disease. The rhesus macaque is already a well-established model for numerous complex human diseases that challenge public health systems world-wide, including addiction and other neuropsychiatric disorders, cardiovascular disease, obesity, diabetes, macular degeneration, cancer, cognitive decline, endometriosis, colitis, and immune senescence, among others. Susceptibility to these complex human diseases is caused by multiple genes, epigenetic dysregulation, the environment, and interaction between these contributing factors. The use of NHPs at the ONPRC as genetic and genomic models for human disease capitalizes on the significant advantages of using this model over similar studies in humans, including close genetic similarity to humans, extensive pedigrees that provide substantial analytical power, a rigorously controlled environment (e.g. diet, housing) which enhances genetic signal over noise, and substantially greater ability to conduct large-scale studies at lower cost.
The Primate Genetics Program capitalizes on resources and investments in new ONPRC faculty to implement cutting-edge genetic and genomic approaches to studying the multifactorial basis of human disease in the NHP model. ONPRC resources that are being leveraged include the rhesus macaque colony pedigree, comprising ~5,000 individuals and spanning 10 generations, accompanying medical health records that provide a wealth of data for exploring the genetic contribution to complex traits, and sample biobanks representing thousands of ONPRC animals. Additional resources include state-of-the-art, next generation sequencing facilities, and a bioinformatics service group dedicated to the establishment of NHP-based analysis pipelines to support WGS, WES, RNA-seq, Methyl-seq, and DNA variant discovery research aims.