Ching-Yi Chen, Ph.D.
Assistant Professor, Department of Biochemistry and Molecular Genetics
Areas of Focus: Post-transcriptional regulation of gene expression, mRNA decay, RNA-binding proteins, knockout mice.
Regulation of mRNA turnover is an important process in determining levels of gene expression. mRNA stability varies considerably from one mRNA species to another and is determined by specific cis-acting elements within the mRNA molecule. mRNAs encoding cytokines and proto-oncogenes are degraded rapidly in order to minimize potentially inflammatory or oncogenic effects that may result from their overexpression. Many of these transcripts contain cis-acting instability elements within their 3' untranslated regions that are believed to activate mRNA decay pathways. The AU-rich elements (AREs) appear to be prominent elements that direct rapid mRNA decay by a process referred to as ARE-mediated mRNA decay (AMD). AMD is regulated by RNA-binding proteins. A number of proteins have been described to bind AREs and are collectively called ARE-binding proteins (ARE-BPs). Decay-promoting ARE-BPs bind ARE-containing mRNAs and target them for decay by recruitment of mRNA decay enzymes.
Our research is directed to understand the mechanisms by which a decay-promoting ARE-BP, KSRP (KH-type Splicing Regulatory Protein), regulates AMD, and to investigate the in vivo functions of Ksrp at the organismal level by using Ksrp knockout mice.
| The research in my laboratory is currently
focused on the following areas:
1) to investigate the role of Ksrp in
post-transcriptional regulation of type I
interferon gene expression and the effect
of Ksrp deficiency on virus infection,
2) to characterize phenotypes associated
with Ksrp deficiency,
3) to identify novel Ksrp mRNA targets by
genome-wide microarray analysis,
4) to identify factors that regulate the
function of Ksrp in ARE-mediated mRNA
decay by a biochemical approach, and
5) to generate a new knockout mouse model
to investigate post-transcriptional regulation
of gene expression at the animal level.
The characterization of Ksrp-null mice should reveal its in vivo function in post-transcriptional control of gene expression and phenotypes associated with the deficiency,and identify physiological mRNAs targeted by Ksrp for decay.
The generation of knockout mouse models should provide insights into the critical role of post-transcriptional regulation in gene expression at the organismal level. In summary, mRNA turnover is a regulated process and represents an important area of gene expression in mammalian cells. Dysregulated turnover of certain mRNAs has been implicated in various pathological processes. Understanding the regulation and dysregulation of mRNA decay in normal cells and in pathological cells, respectively, should help the development of alternative treatments for immune and inflammatory diseases, as well as cancer.
Dr. Ching-Yi Chen (b. 1963) is an Assistant Professor of Biochemistry and Molecular Genetics. Dr. Chen received his B.S. degree from National Cheng Kung University in Taiwan (1986) and Ph.D. degree from Baylor College of Medicine (1996). He then moved to University of California at San Diego and received his postdoctoral training in the laboratory of Dr. Michael Karin, where he was supported by three consecutive postdoctoral fellowships. He joined the faculty as an assistant professor at UAB in 2002.