Spring 2013 Jaconette L. Tietze Young Scientist Award
The Jaconette L. Tietze Young Scientist Research Award is for one year of support of $25,000. Preference will be given to senior postdoctoral fellows nearing independence and/or junior faculty located at the UW who have not yet received major external funding (such as an R01). The research should involve or be relevant to some aspect of stem or progenitor cell biology or therapies.
Jason Berndt, PhD
Acting Instructor, Pharmacology (Moon Lab)
University of Washington
RETINOIC ACID AND WNT/B-CATENIN SIGNALING CREATE A FEEDBACK LOOP IN HUMAN EMBRYONIC STEM CELLS.
Human embryonic stem cells (hESCs) provide a means to study human development and hold great promise for cell-replacement therapies. During differentiation of hESCs, researchers attempt to drive hESCs to specific cell lineages by mimicking the precise spatial and temporal activation of molecular signaling pathways that occurs during embryonic development. One example where significant progress has been made is in the differentiation of hESCs and the related pluripotent cell type, induced pluripotent stem cells (iPSCs), toward neuronal lineages. Cortical neuronal differentiation of hESCs and iPSCs has been shown to recapitulate the step-wise order of differentiation from early neural progenitor cells into all the neuronal cell types of the six layers of the cerebral cortex. Moreover, neuronal differentiation of iPSCs has been used to create in vitro models of human neurological diseases such as, Spinal Muscular Atrophy, Familial Dysautonomia, Alzheimer’s and Parkinson’s disease.
I am interested in the Retinoic acid (RA) and Wnt/ b-catenin (Wnt) signaling pathways. RA and Wnt signaling are critically important for developmental neural patterning in embryos. Moreover, in the germinal centers of the adult brain responsible for ongoing neurogenesis, Wnt signaling is required for the maintenance of neural stem cells. Several labs have found that exogenous retinoids are required for efficient derivation of neural progenitor cells from hESCs. My lab has developed tools that report the level of RA and Wnt pathway activation in hESCs. Using these reporters, I discovered a negative feedback loop; whereby, RA stimulates Wnt signaling, which in turn inhibits RA signaling. The goals of my project are to (1) characterize the functional role of this RA-Wnt feedback loop during neuronal differentiation of hESCs and (2) determine the genes/proteins that govern this interaction using gene expression analysis and gene knockdown experiments. These data will allow us to better understand the molecular determinants of neural cell fate, will improve our ability to enrich for particular neuronal cell types, and may elucidate deficits in signaling associated with human disease-associated genetic mutations.