Our research goals are to advance the fundamental understanding of pluripotent stem cell biology and to explore how failure of genomic integrity impacts human development. We are developing novel live-cell and fixed-cell imaging techniques to study mitotic progression and genomic stability in human pluripotent stem cells. These techniques will be coupled with single cell analysis and computational biology approaches to improve our understanding of how cell cycle regulation and pluripotency are coupled.
The most common and clinically problematic form of genomic instability is aneuploidy, a hallmark of cancer and a cause of infertility and congenital developmental defects. The causes of aneuploidy remain largely unknown, yet the impact on development is profound. Aneuploidy affects 35% of clinically recognized spontaneous abortions, 4% of stillborns and 3 in 1000 live borns. As neonatologists, we witness firsthand the consequences of aneuploidy on development when we care for couples that have struggled with infertility and whose infants are afflicted by genetic syndromes. The long term goal of our research will be to use human pluripotent stem cell research to improve our understanding of early human development and how genomic instability disrupts normal development and contributes to birth defects.