My lab has pioneered various aspects of the microRNA field and continues to make important contributions to this aspect of post-transcriptional control of gene regulation in stem cell development, cancer and aging. For example we are co-discoverers of the second known microRNA, let-7 (Reinhart et al Nature, 2000), and the co-discoverers of the first known human microRNA (Pasquinelli et al. Nature, 2000). We showed that microRNAs indeed base pair with their predicted complimentary sequences in target genes in vivo (Vella et al. Genes Dev, 2004). We showed that a single miRNA can regulate multiple targets in vivo (Grosshans et al. Dev Cell, 2005). We discovered that human let-7 is a critical determinant of lung cancer and that it regulates the important oncogene, RAS (Johnson et al. Cell, 2005). This provided the first mechanism for a microRNAs role in cancer, and helped propel microRNAs in to the spotlight as potential causes and cures for cancer (Esquela-Kerscher and Slack. Nature Rev. Cancer, 2006). We were the first to show in vivo efficacy of delivered microRNAs as anti-cancer agents (Esquela-Kerscher et al., Cell Cycle, 2008), that miRNAs synergize with cancer therapeutics (Weidhaas et al., Can Res. 2007) and that cancer risk factor alleles can lie in miRNA binding sites in cancer genes (Chin et al. Cancer Res. 2008). We also discovered the in vivo function for miR-34 (Kato et al Oncogene 2009). Recently, we discovered that cancers become addicted to microRNA oncogenes (Medina et. al., Nature 2010), setting the stage for targeting microRNAs as cancer therapeutics (Babar et al PNAS 2012). We completed the first sequencing of the microRNAome and 3'UTRome in cancer patients (Chen et al., Oncogene 2014). We discovered that microRNAs regulate lifespan and aging (Boehm and Slack. Science, 2005), and subsequently identified additional gerontomiRs, some of which promote normal lifespan and other that antagonize lifespan (deLencastre et al Current Biol. 2010). We also showed the first role for microRNAs in regulating Alzheimer's Precursor Protein pathways (Niwa et al., Dev Biol. 2008) and as biomarkers of aging (Pincus et al PLOS Gen. 2011). We intend to continue at the forefront of this exciting and emerging field, focusing on miRNAs and their role in stem cell development, aging and cancer. We hope to continue discovering how miRNAs are expressed, what they regulate, how they function, how extensive their reach is, what roles they play in aging and cancer, and harnessing this new mechanism to combat diseases of old age, such as cancer.