Dr Hong Yung

Correct communication among fetus-placenta-mother is crucial for health pregnancy outcome and is largely orchestrated by placentally-derived proteins including hormones. I have previously demonstrated placental endoplasmic reticulum (ER) and mitochondrial stress playing central role in pathophysiology of preeclampsia, fetal growth restriction and gestation diabetes. Epidemiological studies reveal that both mother and her babies born from these complications are at increased risks of developing cardiometabolic diseases in their later life. Secretory and membrane proteins are synthesizing and folding in ER, while ER stress promotes protein misfolding. Can loss of placental signals predispose risk factors to fetus and mother? I have generated several transgenic models, such as junctional zone-specific ER stress (Jz-Perk-/-; Jz-Xbp1-/-) in which ER stress is activated exclusively in the placenta, promoting placenta secreting bio-inactive proteins. I have recently reported that loss of placental signals leads to maladaptation of maternal hepatic glucose metabolism. Next, I will use these transgenic animals to explore and elucidate molecular mechanisms for “programming” fetus and mother for the cardiometabolic diseases and whether alleviation of placental stress acts as therapeutic target.