Regulation of Cell Differentiation by ssDNA/RNA-Binding Proteins
My research group is interested in understanding the molecular mechanisms that lead to phenotypic reprogramming of disease or injury-activated cell types of the heart, lung, and blood vessels. This line of investigation has led us to identify several members of the Pur and Y-box families of single-stranded DNA (ssDNA)/RNA-binding proteins as crucial regulators of muscle gene expression in myofibroblasts, smooth muscle cells, and cardiomyocytes. Our scientific approach is to apply rigorous techniques of physical biochemistry in conjunction with cell-and tissue-based bioassays to test putative models of transcriptional and translational repression by Pur α, Pur β, and YB-1. In vitro experiments are designed to yield quantitative information describing the structural and functional properties of each protein in relation to ssDNA/RNA recognition, gene regulation, and the modulation of cell phenotype. In vivo studies are focused on establishing the physiological role(s) of these unique ssDNA/RNA-binding proteins in mouse models of cardiovascular disease or injury. Over the past 12 years, our work has been supported by grants from the NHLBI and AHA.