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Ching-Yi Chen, PhD

Ching-Yi Chen, PhD
Associate Professor
Department of Genetics
Telephone: (205) 205-934-5073

Biographical Sketch

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 at UAB in 2002.

Research/Clinical Interest

Mechanism and Regulation of Mammalian mRNA Turnover
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.

Selected Publications

  1. Chen, C. Y., Del Gatto-Konczak, F., Wu, Z., and Karin, M. (1998) Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway. Science 280, 1945-1949. 9632395 
  2. Li, X., Lin, W.-J., Chen, C.Y., Si, Y., Zhang, X., Lu, L., Suswam, E., Zheng, L., and King, P. H. (2012) KSRP: A Checkpoint for Inflammatory Cytokine Production in Astrocytes. Glia. 60, 1773-1784.  22847996 
  3. Briata, P., Lin, W.-J., Giovarelli, M., Pasero, M, Chou, C.-F., Trabucchi, M., Rosenfeld, M.G., Chen, C.Y., and Gherzi, R. (2012). PI3K/AKT signaling determines a dynamic switch between distinct KSRP functions favoring skeletal myogenesis. Cell Death Differ. 19, 478–487. 21886180 
  4. Lin WJ, Zheng X, Lin CC, Tsao J, Zhu X, Cody JJ, Coleman JM, Gherzi R, Luo M, Townes TM, Parker JN, Chen CY. (2011) Post-transcriptional control of type I interferon genes by KSRP in the innate immune response against viral infection. Mol Cell Biol. 31, 3196-3207. 21690298 
  5. Maitra, S., Chou, C.-F., Luber, C.A., Lee, K.-Y., Mann, M., and Chen, C.Y. (2008). The AU-rich element mRNA decay-promoting activity of BRF1 is regulated by mitogen-activated protein kinase activated protein kinase 2. RNA 14, 950-959. 18326031 
  6. Lin, W.-J., Duffy, A., and Chen, C.Y. (2007). Localization of AU-rich element-containing mRNA in cytoplasmic granules containing exosome subunits. J. Biol. Chem. 282, 19958-19968. 17470429 
  7. García-Mayoral, M. F., Hollingworth, D., Masino, L., Díaz-Moreno, I., Kelly, G., Gherzi, R., Chou, C.-F., Chen, C.Y., and Ramos, A. (2007). The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA Degradation. Structure 15, 485-498. 17437720  
  8. Ruggiero, T., Trabucchi, M., Ponassi, M., Corte, G., Chen, C.Y., Al-Haj, L., Khabar, KS., Briata, P., and Gherzi, R. (2007). Identification of a set of KSRP target transcripts upregulated by PI3K-AKT signaling. BMC Mol Biol. 16, 28  17437629 
  9. Gherzi, R., Trabucchi, M., Ponassi, M., Ruggiero, T., Corte, G., Moroni, C., Chen, C.Y., Khabar, K.S., Andersen, J.S., and Briata, P. (2007). The RNA-binding protein KSRP promotes decay of -catenin mRNA and is inactivated by PI3K-AKT signaling. PLos Biol. 5, 82-95. 17177604 
  10. Chou, C.-F., Mulky, A., Maitra, S., Lin, W.-J., Gherzi, R., Kappes, J., and Chen, C.Y. (2006). Tethering KSRP, a decay-promoting ARE-binding protein, to mRNAs elicits mRNA decay. Mol. Cell. Biol. 26, 3695-3706. 16648466 
  11. Briata, P., Forcales, S.V., Ponassi, M., Corte, G., Chen, C.Y., Karin, M., Puri, P.L., and Gherzi, R. (2005). p38-dependent phosphorylation of the mRNA decay-promoting factor KSRP controls the stability of selected myogenic transcripts. Mol. Cell 20, 891-903. 16364914 
  12. Gherzi, R., Lee, K.-Y., Briata, P., Wegmüller, D., Moroni, C., Karin, M. and Chen, C.Y. (2004). A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol. Cell 14, 571-583. 15175153 
  13. Briata*, P., Ilengo, C., Corte, G., Moroni, C., Rosenfeld, M.G., Chen*, C.Y., and Gherzi*, R. (2003). The Wnt/ƒÒ-catenin¡÷Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs. Mol. Cell 12, 1201-1211. (*These authors contributed equally to this work) 14636578 
  14. Chen, C. Y., Gherzi, R., Ong, S. E., Chan, E. L., Raijmakers, R., Pruijn, G. J., Stoecklin, G., Moroni, C., Mann, M., and Karin, M. (2001) AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107, 451-464. 11719186 
  15. Chen, C. Y., Gherzi, R., Andersen, J. S., Gaietta, G., Jürchott, K., Royer, H. D., Mann, M., and Karin, M. (2000) Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Genes & Dev. 14, 1236-1248. 10817758