Research in the Taube Lab focuses on the epigenetic regulation of cell identity and it’s relationships to tumor formation and metastasis. Current lab projects are exploring histone modifying enzymes, microRNAs, and small molecule inhibitors of these regulators as well as drug-like natural products.
MicroRNA-203 Reverses EMT and Blocks Metastasis
MicroRNAs are small non-coding RNAs, transcribed from the genome, which have the capacity to regulate hundreds of other transcripts by base-pair binding of a 21 nucleotide sequence to a matching sequence on their target. We have demonstrated that microRNA-203 (miR-203) is strongly repressed by EMT. Re-expression of this microRNA in cells which have undergone EMT reverts them to an epithelial phenotpye, decreases their migratory capacity and prevents metastasis (Taube et al. 2013). We are working to characterize the downstream effectors regulated by miR-203 and the potential utility of elevating miR-203 expression in primary tumors.
Regulators of Histone Methylation Facilitate EMT Reversal
Histones are proteins which facilitate the condensation of DNA in the nucleus. Tight regulation of the accessibility of the DNA is essential for appropriate gene expression. One mechanism underlying this is the post-translational modification of histones, termed the histone code. We have demonstrated that EMT drives genome-wide changes in the histone methylation landscape and that these changes underly the changes in expression of thousands of genes (Malouf and Taube et al. 2013) and that the histone demethylase KDM6A is responsible for remodeling bivalency across the genome in cancer stem cells (Taube and Sphyris et al. 2017). We are working to characterize the specific roles of proteins which ‘write’ the histone code, proteins which ‘read’ the histone code, and proteins that ‘erase’ the histone code.