Basu Lab

Heart Development and CHD

In human pregnancies, there is a significant correlation between maternal pre-existing diabetes and elevated risk of congenital heart defects (CHD) in the offspring of affected mothers. Basu laboratory focuses on understanding the molecular and epigenetic mechanisms of how maternal adverse environment influences the normal heart development in the embryos. Previously, we have identified a gene-environment (GXE) interaction between maternal high glucose environment and haploinsufficiency of Notch1, a key gene required for cardiac morphogenesis. This GXE interaction resulted in increased incidence of septal defects, a most common form of CHD. We also demonstrated an epigenetic mechanism of how Notch1 is regulated in the setting of maternal hyperglycemia. This study also indicated that varying levels of maternal hyperglycemia lead to increased severity and spectrum of CHD, the mechanistic basis of which remains unclear. The lab is currently utilizing in vivo and in vitro transcriptomics, epigenomic and metabolic approaches to examine the cell specific sensitivity towards high glucose levels. The overarching goal of the lab is to identify the impact of maternal hyperglycemia on spatiotemporal regulation of cardiac genes and signaling pathways in the developing fetus and design strategies to prevent maternal diabetes mediated embryopathies.

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