Focus on Lifespan Health. Monkeys and humans share many reproductive and developmental features that emphasize their importance as translational models. Rhesus monkey colonies at the CNPRC parallel the human lifespan, and Unit Core Scientists have a clear dedication to the study of lifespan health from the earliest stages of development through aging populations. The unique expertise in the Unit provides a means to address research questions associated with all developmental stages (embryo, fetus, newborn, infant), juveniles; young adults; pre-menopausal/transitional reproductive stages; and advanced geriatrics. Core Scientists conduct studies on gamete biology and the impact of environmental factors, reproductive and developmental toxicology, utilize unique fetal models of congenital and acquired diseases (e.g., obstructive renal disease, acquired infectious diseases with colleagues in the Infectious Diseases Research Unit), and have unique strengths in gene therapy and stem cell transplantation across the age spectrum. They have also made seminal discoveries on the menopausal transition as it relates to healthy aging that has had a major impact on the field and provided insights of direct relevance to humans.
Research Accomplishments in Reproductive Sciences and Regenerative Medicine
- Developed models for reproductive toxicology including environmental exposure to endocrine-disrupting chemicals and effects of binge alcohol consumption
- Showed that fetal bisphenol A (BPA) exposure at levels similar to those measured in humans can potentially cause reproductive problems that may not emerge for a generation
- Demonstrated that ovarian steroids can change both the structure and function of the adrenal glands, which may explain differences in menopausal symptoms and health trajectories in middle-aged women
- Developed new tissue engineering approaches to regenerate kidneys damaged by obstructive renal disease
- Facilitated a development plan for studies in young monkeys to support an IND application for treating children with Pompe disease
- Assessed safety and gene transfer efficiency of a lentiviral vector that showed a lack of toxicity and no adverse effects in fetal and juvenile monkeys. These studies were critical in gaining approval for an IND application and conducting the first-in-human trial of an expressed siRNA in a lentiviral vector.
- Established novel in vivo imaging tools to monitor gene expression long-term, and showed high levels of reporter gene expression with no adverse effects up through ~10 years of age when organ-targeted fetal gene transfer approaches were used
- Synthesized new radioimmunoconjugates using radioactive copper (64Cu) and zirconium (89Zr) for cell trafficking, and optimized radiolabeling methods to identify engrafted human cells in the rhesus host
- Showed multilineage engraftment after fetal transplantation of cytokine expanded human cord blood CD34+ cells. These findings are significant because they have shown human cells in the rhesus host that persist over time and without pre-transplant conditioning. Bioluminescence imaging has revolutionized monitoring engraftment and the induction of tolerance to transplanted cells.
NHLBI Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases
The NHLBI Center for Fetal Monkey Gene Transfer provides collaborative opportunities to address crucial gaps, and accelerate new NIH grant submissions and IND applications. Read more.
The NHLBI Annual Gene Therapy Symposium for Heart, Lung, and Blood Diseases is currently in the 12th year of NIH support. The intent of these annual interdisciplinary scientific symposia is to provide a novel and informal scientific setting for the dissemination and exchange of new ideas and research findings by bringing together students, fellows, and junior investigators who do not typically interact at other meetings. Trainees are supported through a competitive process and have the opportunity to present their research in a brief oral presentation followed by a poster session, and directly interact with leading scientists in the gene therapy and regenerative medicine fields (www.GTS.ucdavis.edu).
Translational Human Stem Cell Shared Research Facility (TSRF)
The UC Davis Stem Cell Program combines unique capabilities for stem cell research with training in diseases that might be prevented, reversed, or ameliorated by stem cell therapy. The TSRF is a campus-wide service facility dedicated to the study of human stem cells. The facility includes cell culture laboratories, flow cytometry and cell sorting, a molecular core, a histology core, controlled-rate cryopreservation and cell storage for cell lines and cell banks, and an infrastructure of experienced personnel to ensure efficient operation, to provide services, and for training and research guidance (www.tsrf.ucdavis.edu). The TSRF is a centralized location on-site at the Primate Center where collaborating investigators can prepare cells for transplant into nonhuman primates. The Stem Cell Training Program includes a core curriculum linked with the Clinical and Translational Science Center, and weekly journal club for trainees. To learn more about the TSRF, download a pdf here.