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 entire CNS. The Loeken lab seeks to understand the molecular regulation of early neural tube formation, and to understand the mechanisms by which neural tube defects occur in the offspring of diabetic mothers. Using a mouse model, we have demonstrated that neural tube defects (NTDs) result from impaired expression of genes in the embryo that control developmental programs. We have focused on Pax3, a gene that is essential for neural tube closure, how glucose metabolism regulates expression of Pax3, and in how deficient expression of Pax3 leads to NTDs. Using a variety of molecular and genetic approaches, we have shown that Pax3 inhibits p53-dependent apoptosis, apparently by destabilizing p53 protein, during neural tube development, and that neural tube defects in Pax-3-deficient embryos results from derepression of p53-dependent apoptosis.

The current research in my laboratory is focused on understanding how Pax3 is regulated by normal and abnormal metabolism, and how Pax3 regulates aerobic and glycolytic metabolism via p53 function. We are also investigating how glucose metabolism regulates the transition from pluripotency to neural lineage development. Many of these studies are performed using mouse embryonic stem cells during neuronal precursor differentiation.