Our overall research goal is to use molecular and cellular approaches to answer scientifically and clinically pertinent questions regarding human gametes, preimplantation embryos, and totipotent and pluripotent stem cells. We seek to understand genetic, epigenetic and cellular mechanisms governing early human development while first using cutting-edge approaches in appropriate animal models, then applying the resultant information to humans.

The main focus of several ongoing projects is to understand the mechanisms of genetic and epigenetic reprogramming of aged somatic cells to the totipotent and pluripotent states following somatic cell nuclear transfer (SCNT). Specifically, we are interested in the role of mitochondria and mitochondrial (mt)DNA in reprogramming and re-setting the developmental program in experimental pluripotent stem cells derived from aged somatic cells. Another objective is to develop efficient protocols for deriving human pluripotent stem cells via SCNT for patients carrying mtDNA mutations.

Several other projects at the Center are focused on the assessment of the safety and efficacy of stem cell based therapies by transplantation studies in a clinically relevant nonhuman primate model. The overall goal of these studies is to take advantage of recent developments in our Center that allowed for the first time derivation of immuno-matched pluripotent cells by SCNT or iPS approaches, suitable for autologous transplantation into existing monkeys.

Our Center is actively investigating novel germ line gene therapy approaches for the treatment of inherited human diseases. We are focused on answering important safety and efficacy questions regarding techniques that could one day be useful in preventing thousands of inherited genetic disorders that affect millions of people worldwide.

Mutations in mtDNA contribute to a diverse range of still incurable human diseases and disorders including neurodegenerative diseases, myopathies, diabetes, blindness, cancer and infertility. MtDNA is maternally inherited through the egg's cytoplasm, and it is estimated that at least 1 in 200 born children have an mtDNA mutation that may lead to disease. Our team demonstrated that the mitochondrial genome could be efficiently replaced in mature nonhuman primate oocytes by chromosome transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. This discovery lead to the demonstration by our team that the nuclear genetic material from a patient's egg containing mtDNA mutations could be removed, and transplanted into an enucleated egg containing normal mtDNA donated by a healthy female. A child born following fertilization would be free of risk from maternal mtDNA mutations as well as the authentic biological child of the parents. 

Mutations in nuclear genes currently account for 95% of all human diseases including cardiomyopathies, BRCA1 and BRCA2, Huntington's, Cystic Fibrosis, and many more. Using current technologies our research focuses on eliminating disease-causing gene mutations in the human germline in order to prevent transmission to future generations. Our team of scientists continues to pioneer new groundbreaking science while relying on decades of embryology, molecular, and genetic expertise in our Center.

Informed consent of research participants is of paramount importance to OHSU. Please contact us to request copies of  consent forms provided to participants in research conducted by the OHSU Center for Embryonic Cell and Gene Therapy.