Current Research Projects

Projects

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

Studying placenta-associated pregnancy disorders is very difficult, because disease onset happens ;in vivo ;in the uterus. To overcome these challenges, our group has established a model of trophoblast (placental epithelial cells) differentiation using human pluripotent stem cells (hPSC) exposed to 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 called preeclampsia (PE). Preeclampsia not only affects moms, but can also affect their babies during and later in their life. However, we do not have any definitive treatments for PE. We are using our hPSC disease models to understand the pathophysiology of pregnancy complications at the molecular and cellular level and to identify the pathways that can be targeted for disease interventions.

Characterization of PE using clinical, pathological, and transcriptomic analysis

Preeclampsia is a multifactorial pregnancy syndrome, whose pathophysiology involves a combination of maternal and fetal/placental factors. However, most symptoms resolve following the delivery of the placenta, leading to clinically necessitated deliveries. There have been massive efforts to further sub-classify PE 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. Clinically, PE has been categorized by severity of the disease. Pathologically, recent efforts have organized the placental pathologic findings into four major findings in the placenta. Our group is working on the combined analysis of clinical, pathological, immunohistochemical (IHC), and transcriptomic profiling data from a cohort of patients with PE with severe features to identify specific abnormalities at the cellular and molecular levels to identify pathways altered in disease.

Trophoblast stem cells in Trisomy 21

It has been well known that Trisomy 21 (T21) placentas maintain a continuous layer of trophoblast stem cells well into the second trimester. Our group found that T21-affected hPSCs maintains higher and longer expression of the trophoblast stem cell marker, suggesting they may be an effective disease model. Using the T21-affected hPSCs, we are currently trying to understand the mechanism of trophoblast maturation defects in T21-affected placentas.

Collaboration

We are highly collaborative group. A current on-going collaboration includes working with the Parast and Kaufman labs to differentiate decidual natural killer (dNK) cells from patient derived human pluripotent stem cells with the goal of studying trophoblast and dNK interactions.