MicroRNAs (miRNAs) are small non-coding RNAs that posttranscriptionally regulate the expression of protein-coding genes. The discovery of miRNAs has resulted in a paradigm shift in our knowledge about gene control and therapeutic intervention. Through their binding to their target genes, these “master regulators” induce subtle alterations in gene expression that can culminate in major phenotypic changes. This is based on the notion that miRNAs are pleiotropic, referring to the fact that miRNAs can bind to and affect multiple targets. Although the expression of an individual miRNA target may only change marginally, the combined effect of suppressing several targets at the same time results in a phenotypic transformation. This is most clearly illustrated in the context of cancer where miRNA dysregulation contributes to many types of cancer. In some instances the combination of multiple subtle changes causes the tumor cells to become addicted to a single miRNA. MiR-21 and miR-155 are two oncogenic miRNAs (oncomiRs) that have shown this type of addictive pattern in vivo. Similarly loss of key tumor suppressive miRNAs, through epigenetic silencing, genomic loss, and reduced upstream signaling and processing, has been correlated with disease state. Based on this knowledge we have embarked on three very distinct yet equally important areas of miRNA therapeutic biology.

Project 1

project1

Using tumor suppressive miRNAs as cancer therapeutics and sensitizers

Project 2

let7

Restoring let-7 processing through small molecule discovery

Project 3

mouse

Identifying miRNAs that can potentiate tumor formation