RNA biology, noncoding RNAs, and post-transcriptional regulation of gene expression in normal physiology and disease
The Mendell laboratory investigates fundamental aspects of post-transcriptional gene regulation, noncoding RNA regulation and function, and the roles of these pathways in normal physiology, cancer, and other diseases. In addition, we employ high-throughput screening approaches to interrogate diverse problems in RNA and cancer biology.
To briefly summarize some of our most important discoveries, we uncovered the first example of a vertebrate transcription factor that regulates miRNA expression (O’Donnell et al., Nature, 2005). This study, which demonstrated that the MYC oncogenic transcription factor directly transactivates the pro-tumorigenic miR-17-92 cluster, was important for establishing the principle that miRNAs have been functionally integrated into core cancer pathways. Subsequent work from my laboratory further defined the roles of miRNAs in several critical oncogenic and tumor suppressor pathways. Our laboratory has been at the forefront of elucidating miRNA functions in vivo (e.g. Chivukula et al., Cell, 2014) and translating these findings into novel therapeutic approaches, most notably through our demonstration that systemic delivery of miRNAs potently suppresses tumorigenesis in mouse cancer models without toxicity (e.g. Kota et al, Cell, 2009). We have also advanced our understanding of miRNA regulation, identifying examples of regulated miRNA biogenesis, decay, and target engagement (e.g. Hwang et al., Science, 2007; Golden et al., Nature, 2017). Our laboratory has also discovered important long noncoding RNAs (lncRNAs) and dissected their functions in cell and animal models (e.g. Lee et al., Cell, 2016). Most recently, we have employed high-throughput approaches to interrogate RNA biology and post-transcriptional regulation (Golden et al., Nature, 2017), a strategy that we are now applying to diverse problems in the laboratory.