Person
Chung, Bon-chu
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Biography and Research Interest
Research
I. Steroid Function and Regulation
My lab has been working on steroid function and regulation. Recently we have established mouse models to study steroid deficiency. We used a gene-targeting technique to disrupt Cyp11a1, the first gene in steroid biosynthetic pathways. These Cyp11a1 null mice did not synthesize steroids. They died shortly after birth, but could be rescued by steroid injection, yet male mice were feminized with female external genitalia and under-developed male accessory sex organs. In addition, their adrenal and gonads accumulated lipid and gradually degenerated. This provides a good model for the study of steroid deficiency.
II. Zebrafish Development
We have cloned zebrafish genes which play important roles during development. Among them, sox9 is important probably for cartilage development and testis formation. We find the sox9 gene is duplicated in zebrafish. Sox9a and sox9b expression patterns differ, indicating their separate role during development.
We have also characterized the expression and functions of steroidogenic genes, such as cyp11a1, cyp19, and 3-beta-HSD in zebrafish. These genes are mostly duplicated, with one gene expressed in the gonads and brain of zebrafish, similar to the expression pattern of the mammalian steroidogenic genes. The other zebrafish steroidogenic genes are expressed in the yolk syncytial layer during early embryogenesis, indicating the roles of steroids at this stage.
Pregnenolone, the immediate product of Cyp11a1, functions in promoting embryonic cell migration. Pregnenolone does so by binding to and activating a microtubule plus-end-binding protein, CLIP-170, which can promote microtubule polymerization, thus increasing cell motility. Currently we are continuing to investigate the functions of various steroids in zebrafish embryos and their roles in human beings.
I. Steroid Function and Regulation
My lab has been working on steroid function and regulation. Recently we have established mouse models to study steroid deficiency. We used a gene-targeting technique to disrupt Cyp11a1, the first gene in steroid biosynthetic pathways. These Cyp11a1 null mice did not synthesize steroids. They died shortly after birth, but could be rescued by steroid injection, yet male mice were feminized with female external genitalia and under-developed male accessory sex organs. In addition, their adrenal and gonads accumulated lipid and gradually degenerated. This provides a good model for the study of steroid deficiency.
II. Zebrafish Development
We have cloned zebrafish genes which play important roles during development. Among them, sox9 is important probably for cartilage development and testis formation. We find the sox9 gene is duplicated in zebrafish. Sox9a and sox9b expression patterns differ, indicating their separate role during development.
We have also characterized the expression and functions of steroidogenic genes, such as cyp11a1, cyp19, and 3-beta-HSD in zebrafish. These genes are mostly duplicated, with one gene expressed in the gonads and brain of zebrafish, similar to the expression pattern of the mammalian steroidogenic genes. The other zebrafish steroidogenic genes are expressed in the yolk syncytial layer during early embryogenesis, indicating the roles of steroids at this stage.
Pregnenolone, the immediate product of Cyp11a1, functions in promoting embryonic cell migration. Pregnenolone does so by binding to and activating a microtubule plus-end-binding protein, CLIP-170, which can promote microtubule polymerization, thus increasing cell motility. Currently we are continuing to investigate the functions of various steroids in zebrafish embryos and their roles in human beings.
Non-Zebrafish Publications
Wu D–A, Chung B–c, Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity respectively. J. Clin. Invest. 88, 519-523 (1991).
Chou S-J, Lai K-N, Chung B-c, Characterization of the upstream sequence of the human CYP11A1 gene for cell type-specific expression. J. Biol. Chem. 271, 22125-22129 (1996).
Hu M-C, Hsu N-C, Ben El Hadj N, Pai C-I, Chu H-P, Wang C-KL, Chung B-c, Steroid Deficiency Syndromes in Mice with a Targeted Disruption of Cyp11a1. Mol. Endocrinol. 16, 1943-1950 (2002).
Chen W-Y, Weng J-H, Huang, C-C, Chung B-c, Histone deacetylase inhibitors reduce steroidogenesis through SCF-mediated ubiquitination and degradation of Steroidogenic Factor 1 (NR5A1). Mol. Cell. Biol. 27, 7284-7290 (2007)
Wang C-Y, Kao Y-H, Lai P-Y, Chen W-Y, and Chung B-c, Steroidogenic Factor-1 (NR5A1) Maintains Centrosome Homeostasis in Steroidogenic Cells by Restricting Centrosomal DNA-PK Activation. Mol Cell Biol, 33, 476-484 (2013).
Huang S-C, Lee C-t, Chung B-c, Tumor Necrosis Factor Suppresses NR5A2 Activity and Intestinal Glucocorticoid Synthesis to Sustain Chronic Colitis. Sci Signal, 7 (314), ra20, 1-11 (2014).
Wang C-Y, Huang EY-H, Huang S-C, and Chung B-c, DNA-PK/Chk2 induces centrosome amplification during prolonged replication stress. Oncogene, Mar 24. doi: 10.1038/onc.2014.74. (2014)