Our Science – Lal Website
Ashish Lal, Ph.D.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally by decreasing the stability or translation of target mRNAs. Recent evidence has linked miRNAs to a number of diseases ranging from myocardial infarction to cancer, highlighting their role in disease pathogenesis. The human genome contains ~ 700 miRNAs. However, the targets and biological role of most miRNAs are still unknown. The focus of our laboratory is to investigate the function and regulation of specific miRNAs in normal and cancer cells.
Mammalian miRNAs bind to target mRNAs via partial complementarity. A single miRNA can regulate the expression of hundreds of mRNAs and due to partial miRNA-mRNA base-pairing, identifying miRNA targets is extremely challenging (Thomas et al., Nat Str Mol Biol, 2010). Recently, we have developed a biochemical approach to identify the mRNAs bound to an endogenous miRNA (Lal et al., PLoS Genet, 2011). Combining this strategy with bioinformatics identifies the networks of genes and canonical pathways regulated by a miRNA. Our initial goal is to uncover the function and regulation of miRNA clusters that we have recently found to be upregulated during cellular differentiation (Lal et al., Mol Cell 2009; Lal et al., Nat Str Mol Biol 2009) and deregulated in several cancers. We will employ a combination of biochemical and systems biology approaches to identify the targets and pathways regulated by these miRNA clusters followed by functional studies. Furthermore, we will use mouse genetic approaches to decipher the function of these miRNAs in vivo and also identify the promoters and transcription factors that regulate their expression. This is a critical question in the miRNA field given the fact that most mammalian miRNAs are encoded by polycistronic transcripts but the regulation and function of individual miRNAs of a cluster and the cluster as a whole are not understood. We hypothesize that miRNAs coexpressed from a cluster regulate multiple genes in the same or similar pathways and thereby control a biological process.
Parallel to these studies we are also interested in specific miRNAs that exhibit context-dependent function. Using molecular and bioinformatic approaches we will investigate the molecular mechanisms underlying the context-dependent function of these miRNAs. In addition to these studies, we will perform miRNA screens to discover novel functions of miRNAs. Accomplishing these goals will provide a framework for understanding how specific cancer-associated miRNAs function and will uncover their usefulness in cancer diagnosis, prognosis and therapy.
This page was last updated on 2/20/2013.