California's Stem Cell Agency

The aim of this project is to screen large collections of small molecules to identify molecules that allow one to propagate human embryonic stem cells (hESCs) in cell culture under defined conditions in an undifferentiated, pluripotent state. The chemical structures of any biologically active small molecules will be optimized with respect to potency, selectivity and biological stability. The ability of hESCs proliferated in the presence of such small molecules to be differentiated into specific cell lineages both in cell culture and in vivo will also be assessed. And finally, we will determine the mechanism of action of active small molecules by a variety of biochemical and genomic methods. The demonstration that one can identify synthetic drug-like molecules that allow one to control the self-renewal and/or differentiation of hESCs will represent an important step in the ultimate therapeutic application of hESCs to human disease. In addition, biological studies of such molecules should provide new insights into the processes that control stem cell biology.