Principal Investigator Harvey Lodish
Researchers are working on identification of genes essential for glucocorticoid mediated BFU-E self-renewal. His current research focuses on functional characterization of one gene that is indispensible for BFU-E self-renewal. This gene is normally downregulated during differentiation from BFU-E stage to CFU-E stage. In our in vitro primary “BFU-Es” culture system, glucocorticoid addition blocked this downregulation and knockdown of this gene by shRNAs completely disrupted glucocorticoid mediated BFU-E self-renewal, but without any effects on cell division rates or cell survival. In our GR Chip-Seq dataset, the activated glucocorticoid receptor binds to a genomic region several kb upstream of the transcription start site of this gene, and a luciferase reporter assay demonstrated that this region is indeed glucocorticoid inducible. These data suggest this gene as a direct transcriptional target of GR. Now Lingbo is trying to understand how this gene is involved in BFU-E self-renewal regulation. In summary, this work will uncover the molecular mechanism how glucocorticoids control BFU-E self-renewal and how glucocorticoid treatment benefits Diamond-Blackfan Anemia and potentially other EPO unresponsive anemias.