Chang-Zheng Chen
Research Interests
We study the genetic networks controlled by regulatory RNAs, such as microRNAs (miRNAs), and currently focus on two complementary aspects of miRNA biology: (1) The roles of miRNAs in modulating the development, function, and pathogenesis of vertebrate immune systems and (2) the mechanisms by which these regulatory RNAs control gene expression.
[Mechanisms of Action by MicroRNA Genes]
We have found that miRNA genes encoding identical or nearly identical mature miRNAs can have distinct biological activities that are determined by their pre-miRNA loop nucleotides. These findings demonstrate that mature miRNAs and their corresponding coding genes are not functionally equivalent and reveal the previously unappreciated regulatory complexities encoded in miRNA genes. We will characterize regulatory controls encoded in the miRNA genes and investigate the mechanisms by which these regulatory elements control the activity of miRNA genes using integrated genetic, biochemical, and bioinformatics approaches.
[Immune Regulation by MicroRNA Genes]
The homeostasis of the immune system is under exquisite quantitative regulation: The number of stem/progenitor cells, the cell cycle progression, the rate of cell division, and the kinetics of lineage differentiation are all closely regulated. We have found that miRNAs may play important roles in controlling many of these quantitative processes, such as lineage differentiation and antigen receptor signaling. We study the function of miRNA genes in the development and function of immune cells and the maintenance of central and peripheral tolerance. We hope that our studies will ultimately shed light on how to modulate immune cell development and function by “dialing” the miRNA rheostats.
[Regulation of Stem Cells by MicroRNA Genes]
Little is known about the role of post-transcriptional regulation in stem cell self-renewal and fate determination. Recent discoveries suggest that miRNAs play a key role in controlling the post-transcriptional genetic programs in stem and progenitor cells. We plan to examine the role of miRNA genes in controlling development and function of the normal and aberrant stem cells.
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