Mariko Horii, MD, PhD

Establishment of disease-in-a-dish model using human pluripotent stem cells (hPSC)

Studying placenta-associated pregnancy disorders is very difficult, because disease originates early in gestation within the uterus. To overcome these challenges, our group has established a model of trophoblast (placental epithelial cells) differentiation using human pluripotent stem cells (hPSC) treated with Bone Morphogenic Protein 4 (BMP4). We found that these cells can recapitulate normal trophoblast differentiation and can be used to model abnormal differentiation.

We are currently focusing on the hypertensive pregnancy disorders, particularly preeclampsia (PE). Preeclampsia not only affects moms but can also affect their babies during and later in their life. However, there are currently no definitive treatments for PE. We are using our hPSC-baseddisease models to understand the molecular and cellular mechanisms underlying pregnancy complications and to identify the pathways that can be targeted for disease interventions.

Characterization of Hypertensive disorder of pregnancy using clinical, pathological, and transcriptomic analysis

Hypertensive disorder of pregnancy is a multifactorial pregnancy syndrome, whose pathophysiology involves a combination of maternal and fetal/placental factors. However, most symptoms reverse back to pre-pregnancy statefollowing the delivery of the placenta, suggesting placenta to be an important factor to the development of this disease. There have been massive efforts to characterize hypertensive disorder of pregnancy to advance our understanding of the underlying pathophysiology of this disease, and in turn, lead to development of more targeted disease predictive markers and subtype-specific interventions. Our group is working on the combined analysis of clinical, pathological, immunohistochemical (IHC), and transcriptomic profiling data from a cohort of patients with hypertensive disorder of pregnancy to identify specific abnormalities at the cellular and molecular levels to identify pathways altered in disease. We will also utilize our iPSC-based disease modeling system to elucidate the disease mechanism at trophoblast cellular level.