Transcriptional regulation in response to environmental and developmental cues is mediated by the combinatorial and synergistic action of specific DNA-binding activators and repressors on components of the general transcription machinery and chromatin modifying activities, and it also involves microRNAs. We combine genetic, molecular, genomic, and evolutionary approaches to address fundamental questions about transcriptional regulatory mechanisms in yeast as well as elucidating the transcriptional regulatory circuits that mediate the process of cellular transformation and formation of cancer stem cells.
Relationship between transcriptional regulatory mechanisms and chromatin structure in yeast: Current projects include 1) how co-activators, chromatin-modifying complexes, repressors, and components of the basic transcription machinery are recruited to promoters in vivo under genetically and environmentally defined conditions, 2) intrinsic and dynamic aspects of chromatin structure, and mechanisms of epigenetic inheritance of heterochromatic and euchromatic states, 3) distinguishing between biological function and biological noise using evolutionarily related yeast species and other approaches.
Transcriptional regulatory circuits during the process of cellular transformation in human cells: Current projects include 1) an epigenetic switch from non-transformed to transformed cells in response to a transient inflammatory signal, 2) molecular pathways required for the formation of cancer stem cells, 3) role of microRNAs at various stages of cellular transformation including potential connections to chromatin, 4) mechanistic analysis of the connection between lipid metabolism and transformation, 5) testing metformin as a potential anti-cancer drug.
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