Women with diabetes have a significantly increased risk of having a baby with a birth defect, especially neural tube defects (NTDs) such as spina bifida. The Loeken lab is studying the molecular and biochemical causes of these NTDs in order to identify potential novel interventions.

The neural tube forms the scaffolding upon which the central nervous system forms. Therefore, proper formation of the neural tube is essential for successful development of the brain and spinal cord. We have shown that excess glucose transported to the embryo during maternal diabetes disturbs the metabolism that is crucial in formation of the neural tube and alters expression of genes that regulate neural tube closure. In particular, expression of Pax3, a gene that is essential for neural tube closure, is significantly impaired. Current experiments are performed using a combination of mouse strains, as well as embryonic stem cells that can be induced to differentiate to neuronal precursors. We are investigating how Pax3 chromatin is regulated during differentiation and during metabolic responses to high glucose, such as oxidative stress, and additional pathways by which excess glucose transport to the embryo could cause NTDs.