Our overall research goal is to use molecular and cellular approaches to answer scientifically and clinically pertinent questions regarding gamete, embryo and stem cell biology. 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 in the lab 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 lab 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 lab is also investigating novel germ line gene therapy approaches for the treatment of inherited human diseases. Particularly, 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 recently 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 suggest 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 with the husband's sperm would be free of risk from maternal mtDNA mutations as well as the authentic biological child of the patients. The overall goal of ongoing research initiative in our lab is to replicate monkey studies with human oocytes donated by patients carrying mtDNA mutations after informed consent.  Healthy egg donors that commit to donating their oocytes for research will be used as mtDNA donors.