Biochemistry and Structural Biology  http://www.gbs.uab.edu  http://www.uab.edu/graduate

Faculty Detail   
Name
 
Campus Address
Phone  
E-mail  
Other websites
    

 Education

Graduate  Baylor College of Medicine    1996  Ph.D. 

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
Title
Post-transcriptional regulation of adipocyte lipid metabolism and type 2 diabetes
Description
Post-transcriptional regulation plays an important role in determining levels of gene expression. KH-type splicing regulatory protein (KSRP), an RNA-binding protein, regulates post-transcriptional gene expression at multiple levels including splicing, mRNA stability, translation, and pri-miRNA processing. We are determining the in vivo functions of KSRP using KSRP knockout mice. The goals of our research are: 1) to understand the role of KSRP in glucose and insulin homeostasis, 2) to understand the roles of miR-150 and miR-145 in whole-body metabolism and adipocyte functions, and 3) to understand the role of KSRP-related RBP family in post-transcriptional regulation of gene expression. Obesity and its related disorders have become a major public health concern in developed countries as it increases the risk of diabetes, heart disease, and some forms of cancer. Defects in insulin signaling are among the most common defect predisposing an individual to the development of type 2 diabetes. As obesity and type 2 diabetes still pose growing therapeutic challenges in industrialized societies, identification of the factors governing adipocyte lipid metabolism and insulin/AKT signaling should lead to a better understanding of the development of obesity and its related disorders. The contributions of our research are expected to be 1) detailed understanding of how KSRP controls glucose homeostasis through the effects on insulin/AKT signaling, 2) detailed understanding of how miR-150 and miR-145 control adipocyte lipid metabolism and whole-body adiposity, and 3) understanding of post-transcriptional regulation of gene expression by FBP family. These contributions are significant because our research is expected to identify novel factors governing adipocyte functions and insulin signaling that may provide future therapeutic targets to control obesity-related disorders and type 2 diabetes.

Selected Publications 
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 
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., 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.    
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.   
 

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