About the Reproductive Sciences and Regenerative Medicine Unit
Unit Core Scientists contribute to the CNPRC mission through NIH-supported research programs and peer-reviewed publications; services to the greater research community in Cores, NIH-supported Centers, and outreach programs; and by enhancing the nonhuman primate resource through model development, innovative in vivo imaging paradigms, and assisting with the management of the nonhuman primate colonies. Core Scientists mentor the next generation of investigators in the use of nonhuman primate models for human health and disease, and serve as collaborative hubs and in the formation of multidisciplinary partnerships and teams. Core Scientists have leadership positions in the UC Davis Clinical and Translational Science Center, West Coast Metabolomics Center, Stem Cell Program, and Center for Health and the Environment. Unit scientists bring their unique expertise and strong track records to collaborative multidisciplinary partnerships that converge on studies focused on early onset disease (e.g., viral teratogens, environmental agents, role of the immune system); regenerative medicine (e.g., stem cell transplantation, tissue engineering) and gene therapy; lifespan health–from the earliest developmental stages to aging populations; in vivo imaging technologies for precision medicine; and preclinical and investigational new drug (IND)-enabling studies for clinical translation. The depth and breadth of expertise, accomplishments, and services of the Unit scientists contribute substantially to the CNPRC mission, significantly enhance the resource, and ensure that investigators nationwide have the guidance and collaborative opportunities necessary to conduct innovative state-of-the-art investigations with nonhuman primates at the highest quality level for solving significant human health problems.
Focus on Lifespan Health. Monkeys and humans share many reproductive and developmental features that emphasize their importance as translational models. 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.
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
- Developed a tissue-engineered replacement for tracheal stenosis with autologous stem/progenitor cells and donor decellularized trachea
- Facilitated a development plan for studies in young monkeys to support IND applications 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 ~12 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.
- Leveraged the fetal rhesus CMV model (in collaboration with Infectious Diseases colleagues) to rapidly respond to the need to understand the emerging viral teratogen, Zika virus, and Congenital Zika Syndrome
- Novel techniques for precision primate models using gene editing (e.g., pre-implantation embryos, somatic models with established pregnancies, therapeutic somatic cells)
- Development and application of translational total-body PET imaging systems for nonhuman primate research
- Improved and characterized detection limits for tracking radiolabeled stem/progenitor cells with PET
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 16th 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 Pluripotent 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 state-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.