Howard Hughes Medical Institute President
Research in our laboratory is directed towards understanding the gene regulatory factors that govern whether embryonic stem cells maintain pluripotency or differentiate. Until recently, it was believed that tissue-specific enhancer binding transcription factors interacted with a general transcription machinery that was universal and invariant between cell types. However, it is now clear that the core transcription machinery can contain components that are cell-type specific. Through biochemical purification and structural studies, reconstituted in vitro transcription reactions and whole genome analyses, we have identified three novel multi-subunit co-factors critical to stem cell self-renewal and differentiation. Current projects in the laboratory include characterization of co-activator complexes that interacts with Oct4 and Sox2 to induce Nanog gene expression in self-renewing human embryonic stem cells, and the role of specific TAFs in the differentiation of various mature differentiated cell-types including skeletal muscle, adipocytes and motor neurons. In addition, we have been developing single cell and single molecule super resolution light microscopy to track and study the process of transcriptional regulation in stem cells. Most recently, we have applied the CRSPR genome editing platform to manipulate gene expression and generate new cell systems to probe in vivo mechanisms of gene control in ESCs.