My laboratory research is broad-based, with an emphasis on gene regulation by chromatin-based mechanisms and changes in the genome that take place during mammalian development. Emphasis is given to developing and using new methods for studying and controlling mammalian gene expression, especially during development in tissue culture from a stem or progenitor cell to a mature adult cell. Recent studies, some still ongoing, have included measuring genome-wide DNA methylation patterns, and changes in these patterns, during cancer progression or normal development.
I am particularly interested in improving the efficiency with which embryonic stem cells (ESC), both mouse and human, can be guided towards mature somatic cells, such as insulin-producing beta cells or cardiomyocytes. Three approaches are currently being explored (i) second generation antisense oligonucleotides (ASOs), (ii) transcription factors fused to novel protein transduction domains, and (iii) epigenetic engineering of ESC by gene-specific DNA methylation or demethylation to limit differentiation to the desired pathway. The latter studies are making use of TALES (Transcription Activation Like Effectors) and CRISPRS (Clustered Regularly Interspaced Palindromic Repeats) to produce mutant cell lines and engineer epigenetic changes in cells and mice.