Back to Main

Faculty Detail    
Campus Address KAUL 440A
Phone  205-934-5073
Other websites

Graduate  Baylor College of Medicine    1996  Ph.D. 

Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Associate Professor
Center  Center for AIDS Research  Center for AIDS Research Associate Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering Associate Professor
Center  Nutrition Sciences   Nutrition Obesity Res Ctr (NORC) Associate Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 

Biographical Sketch 
Dr. Ching-Yi Chen (b. 1963) is an Associate 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 
Publication PUBMEDID
Chou, C.-F., Zhu, X., Lin, Y.-Y.1, Gamble, K.L., Garvey, W.T., and Chen, C.Y. (2015). KSRP is critical in governing hepatic lipid metabolism through controlling Per2 expression. J. Lipid Res. 56, 227-240.    
Bollmann, F., Art, J., Henke, J., Schrick, K., Besche, V., Bros, M., Li, H., Siuda, D., Handler, N., Bauer, F., Erker, T., Behnke, F., Mönch, B., Härdle, L., Hoffmann, M., Chen, C.Y., Förstermann, U., Dirsch, V.M., Werz, O., Kleinert, H., Pautz, A. (2014). Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity. Nucleic Acids Res. 42, 12555-12569.   
Giovarelli, M., Bucci, G., Ramos, A., Bordo, D., Wilusz, C.J., Chen, C.Y., Puppo, M., Briata, P., Gherzi, R. (2014). H19 long noncoding RNA controls the mRNA decay promoting function of KSRP. Proc. Natl. Acad. Sci. USA. 111, [Epub ahead of print]   
Chou, C.-F., Lin, Y.-Y., Wang, H.-K., Zhu, X., Giovarelli, M., Briata, P., Gherzi, R., Garvey, W.T., and Chen, C.Y. (2014). KSRP Ablation Enhances Brown Fat Gene Program in White Adipose Tissue through Reduced miR-150 Expression. Diabetes. 63, 2949-2961.   
Lin, Y.-Y., Chou, C.-F., Giovarelli, M., Briata, P., Gherzi, R., and Chen, C.Y. (2014). KSRP and MiR-145 Are Negative Regulators of Lipolysis in White Adipose Tissue. Mol. Cell. Biol. 34, 2339-2349.   
Bird, C.W., Gardiner, A.S., Bolognani, F., Tanner, D.C., Chen, C.Y., Lin, W.J., Yoo, S., Twiss, J.L., Perrone-Bizzozero, N. (2013) KSRP Modulation of GAP-43 mRNA Stability Restricts Axonal Outgrowth in Embryonic Hippocampal Neurons. PLoS One 8, e79255.   
Chou, C.F., Lin, W.J., Lin, C.C., Luber, C.A. Godbout, R., Mann, M. and Chen, C.Y. (2013) DEAD Box Protein DDX1 Regulates Cytoplasmic Localization of KSRP. PLoS One 8, e73752.   
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 
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 
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 
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 
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 
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  
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 
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 
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 
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 
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 
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 
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 
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 
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 

Post-transcriptional regulation, RNA-binding protein, Adipocyte function