Grant: Operating Grant

Embryonic stem (ES) cells are obtained from microscopic embryos that are barely larger than the tip of a pin. Much like the embryos from which they are derived, ES cells have the capacity to give rise to all of the cell types of the body, in a process known as differentiation. The capacity or "potency" of ES cells to differentiate into a broad variety of cell types is termed pluripotency. When maintained under the appropriate conditions, ES cells can make exact copies of themselves in a process known as self-renewal, which provides a means for large-scale expansion of the total number of ES cells in cell culture. ES cells or very similar cells called induced pluripotent stem cells (iPS cells), which are commonly derived from skin cells, provide a unique starting source of cells that could be used to make any desired cell type for the purposes of repairing or replacing damaged cells in "regenerative medicine" applications. Dr. Doble's research is focused on understanding the mechanisms controlling the process of ES cell/ iPS cell self-renewal and differentiation into specific cell types. The cellular "program" that controls the properties of an individual cell type is executed, in part, by specific molecules called transcription factors, which can read information from the cellular program and "transcribe" it into messages that cells can understand and act on. Dr. Doble is studying a family of transcription factors called Tcf/Lef factors that are important in regulating cell fate decisions during differentiation processes. The details regarding how this family of factors works together to transcribe specific messages in a cell-specific context remain unclear. Dr. Doble's work will not only provide new insights regarding ES cell self-renewal and differentiation, it will also provide information relevant to numerous human cancers in which Tcf/Lef activities are improperly regulated.