Controlling gene expression is essential to growth, development, and sustained life. This requires regulating the spacial, temporal, and developmental expression of genes in a wide diversity of cell types. Our research program focuses on two primary points of control: transcription of messenger RNA (mRNA) and post-transcriptional regulation of mRNAs by microRNAs (miRNAs).
A critical control point for regulating gene expression is at the level of transcription. The proper regulation of transcription is essential for maintaining normal pathways of cell growth and differentiation, thereby avoiding the rampant cell proliferation observed in tumors. Transcriptional regulation is accomplished through complex macromolecular interactions, and understanding regulatory mechanisms requires elucidating the biophysical parameters that govern these interactions. This is a primary goal of our single molecule studies. We also strive to understand transcriptional regulation in cells. We investigate programmed transcriptional responses to external stimuli and stress, which allow cells to adapt to changing environmental conditions. Using heat shock as a model system, we are studying the mechanisms that govern genome-wide changes to transcription in response to stress.
Post-transcriptional control of gene expression can occur through miRNAs, which downregulate gene expression to control cell fate decisions. miRNA mis-regulation contributes to multiple pathologies, underscoring its importance in tightly regulating gene expression. Essential to understanding the mechanisms by which any miRNA controls a cellular processes is knowing the full set of target mRNAs that it downregulates, which of these targets strongly impact cellular phenotype, and how miRNAs themselves are post-transcriptionally regulated. Addressing these issues are primary goals of our work.