研究方向

我的實驗室主要以組織/細胞特異性基因剔除小鼠(conditional knockout mouse)為動物模式，探討基因在發育及癌症形成所扮演的角色。在發育相關的研究，目前有心臟血管及造血幹細胞之生長和分化的小鼠模式，依所觀察到的缺陷性狀探討參與其中重要基因調控及訊息傳導。在癌症形成方面，主要探討肝癌的致病過程及訊息傳導，我們也建立以diethylnitrosamine (DEN)誘導肝癌發生的小鼠模式來模擬人類肝癌發生的狀況。利用細胞特異性基因剔除小鼠模式，我們分析基因在肝臟中不同類型的細胞，包括肝細胞 (hepatocyte)、肝竇內皮細胞(liver sinusoidal endothelial cells)及庫佛氏細胞(kupffer cells)，在肝臟的生理恆定及肝癌發生的過程所扮演的角色。希望我們建立的基因剔除鼠資源得以用來研究發育缺陷成因、器官生理恆定及細胞癌化之重要分子調控。

Transgenic and knockout mice are powerful model systems for understanding embryonic development and disease progression. In the past, several knockout mouse models have been established in my laboratory. In combination with molecular and biochemical approaches, these mouse models are valuable tools for dissecting the mechanisms of the developmental defects (craniofacial and cardiovascular defects) and tumorigenesis (cancer initiation and the effects of diet or carcinogens on cancer promotion and progression).

研究著作

J. -W. Lin, Y. -M. Huang, Y. -Q. Chen, T. -Y. Chuang, T. -Y. Lan, Y. -W. Liu, H, -W, Pan, L. -R. You, Y. -K. Wang, K. -H. Lin, A. Chiou, J. -C. Kuo. 2021. Dexamethasone accelerates muscle regeneration by modulating kinesin-1-mediated focal adhesion signals. Cell Death Discov. 7:35.

J. -R. Fan, L. -R. You, W. -J. Wang, W. -S. Huang, C. -T. Chu, Y.-H. Chi, H. -C. Chen. 2020. Lamin A‐mediated nuclear lamina integrity is required for proper ciliogenesis. EMBO Reports, e49680.

C. L. Hochstetler, Y. Feng, M. Sacma, A. K. Davis, M. Rao, C. Y. Kuan, L. -R. You, H. Geiger, Y. Zheng. 2019. KRas^G12D expression in the bone marrow vascular niche affects hematopoiesis with inflammatory signals. Exp Hematol. 79: 3-15.

C. -H. Chan, C.-M. Chen, Y. -H. Wu Lee, and L. -R. You. 2019. DNA damage, liver injury, and tumorigenesis: consequences of DDX3X loss. Mol. Cancer. Res. 17:555-566.

W. -L. Tu, L. -R. You, A. -P. Tsou, and C. -M. Chen. 2018. Pten haplodeficiency accelerates liver tumor growth in miR-122a–null mice via expansion of periportal hepatocyte-like cells. Am J Pathol. 188: 2688-2702.

W-H Hsu, C-M Chen, L. -R. You. 2017. COUP-TFII is required for morphogenesis of the neural crest-derived tympanic ring. Sci Rep. 7:12386.

H. -K. Li, R. -T. Mai, H. -D. Huang, C. -H. Chou, Y. -A. Chang, Y. -W. Chang, L. -R. You, C. -M. Chen and Y. -H. Wu Lee. 2016. DDX3 represses stemness by epigenetically modulating tumor-suppressive miRNAs in hepatocellular carcinoma. Sci Rep. 6: 28637.

C. -Y. Chen, C. -H. Chan, C. -M. Chen, Y. -S. Tsai, T. -Y. Tsai, Y. -H. Wu Lee and L. -R. You. 2016. Targeted inactivation of murine Ddx3x: essential roles of Ddx3x in placentation and embryogenesis. Hum. Mol. Genet. 25: 2905-2922.

C. -C. Liang, T. -L. Lu, Y. -R. Yu, L. -R. You, C. -M. Chen. 2015. β-catenin activation drives thymoma initiation and progression in mice. Oncotarget 6:13978-13993.

Y. -R. Yu, L. -R. You, Y. -T. Yan, C. -M. Chen. 2014. Role of OVCA1/DPH1 in craniofacial abnormalities of Miller-Dieker syndrome. Hum. Mol. Genet. 23:5579-5596.

C. -C. Liang, L. -R. You, J. J. Y. Yen, N. -S. Liao, H. -F. Yang-Yen, C. -M. Chen. 2013. Thymic epithelial [beta]-catenin is required for adult thymic homeostasis and function. Immunol Cell Biol 91: 511-523.

W. -H. Hsu, Y. -R. Yu, S. -H. Hsu, W. -C. Yu, Y. -H. Chu, Y. -J. Chen, C. -M. Chen and L. -R. You. (2013) The Wilms’ tumor suppressor Wt1 regulates Coronin 1B expression in the epicardium. Exp Cell Res 319: 1365-1381.

T. -L. Lu, Y. -F. Huang, L. -R. You, N. -C. Chao, F. -Y. Su, J. -L. Chang, C. -M. Chen. (2013) Conditionally Ablated Pten in Prostate Basal Cells Promotes Basal-to-Luminal Differentiation and Causes Invasive Prostate Cancer in Mice. Am J Pathol. 182, 975-991.

W. -C. Chiu, J. -Y. Lin, T. -S. Lee, L. -R. You and A. -N. Chiang. (2013) β₂-Glycoprotein I inhibits VEGF-induced endothelial cell growth and migration via suppressing phosphorylation of VEGFR2, ERK1/2, and Akt. Mol Cell Biochem. 372, 9-15.

F. -J. Lin*, L. -R. You¹, C. -T. Yu, W. -H. Hsu, M. -J. Tsai¹1. (2012) Endocardial Cushion Morphogenesis and Coronary Vessel Development Require COUP-TFII. Arterioscler Thromb Vasc Biol. 32, e135-146. (* equal contribution; ¹co-coresponding author)

C. -M. Chen, T. -L. Lu, F. -Y. Su and L. -R. You. (2012) Susceptibility of Epithelium to PTEN-Deficient Tumorigenesis, Tumor Suppressor Genes, Yue Cheng (Ed.), ISBN: 978-953-307-879-3, InTech, Available from: InTechOpen

T. -C. Wei, H. -Y. Lin, C. -C. Lu, C. -M. Chen and L. -R. You. (2011) Expression of Crip2, a LIM-domain-only protein, in the mouse cardiovascular system under physiological and pathological conditions. Gene Expr Patterns 11, 384-394.

H. -P. Huang, C. -L. Hong, C. -Y. Kao, S. -W. Lin, S. -R. Lin, H. -L. Wu, G. -Y. Shi, L. -R. You, C. -L. Wu and I. -S. Yu. (2011) Gene targeting and expression analysis of mouse Tem1/endosialin using a lacZ reporter. Gene Expr Patterns 11, 316-326.

C. -M. Chen, H. -Y. Wang, L. -R. You, R. -L. Shang and F. -C. Liu. (2010) Expression analysis of an evolutionary conserved metallophosphodiesterase gene, Mpped1, in the normal and β-catenin-deficient malformed dorsal telencephalon. Dev. Dyn. 239, 1797-1806.

C. -C. Liang, L. -R. You, J. -L. Chang, T. -F. Tsai and C. -M. Chen. (2009) Transgenic mice exhibiting inducible and spontaneous Cre activities driven by a bovine keratin 5 promoter that can be used for the conditional analysis of basal epithelial cells in multiple organs. J Biomed. Sci. 16, 2.

T. -L. Lu., J. -L. Chang., C. -C. Liang, L. -R. You and C. -M. Chen. (2007) Tumor Spectrum, Tumor Latency and Tumor Incidence of the Pten-Deficient Mice. PLoSone, e1237.

L. -R. You, N. Takamoto, C. -T. Yu, T. Tanaka, T. Kodama, F. J. DeMayo, S. Y. Tsai and M. -J. Tsai. (2005) Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc Natl Acad Sci U S A. 102, 16351-16356.

M. -J. Tsai, L. -R. You, SY. Tsai. (2005) Surprise in the Battle Field of Vein vs. Artery. Organogenesis 2, 31-32.

M. -J. Tsai,L. -R. You, F. -J. Lin and S. Y.Tsai. (2005) Essential role of COUP-TFII in vascular formation. Kidney Int. 68, 1962-1963.

L. -R. You, F. -J. Lin, C. T. Lee, F. J. DeMayo, M. -J. Tsai and S. Y. Tsai. (2005) Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature 435, 98-104.

N. Takamoto, L. -R. You, K. Moses, C. Chiang, W. E. Zimmer. R. J. Schwartz, F. J. DeMayo, M. -J. Tsai and S. Y. Tsai. (2005) COUP-TFII is essential for radial and anterior-posterior patterning of the stomach. Development 132, 2179-2189.

S. -Y. Chen, C. -F. Kao, C. -M. Chen, C. -M. Shih, M. -J. Hsu, C. -H. Chao, S, -H. Wang, L. -R. You and Y. -H. Wu Lee. (2003) Mechanisms for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein. J. Biol Chem. 278, 591-607.

T. J. Jaw, L. -R. You, P. S. Konepfler, L. -C. Yao, C. -Y. Pai, C. -Y. Tang, , L. -P. Chang, Berthelsen, J., Kamps, M. P. and Y. H. Sun. (2000) Direct interaction of two homeoproteins, Homothorax and Extradenticle, is essential for EXD nuclear localization and function. Mech. Dev. 91, 279-291.

L. -R. You, C. -M. Chen, T. -S. Yeh, T, -Y. Tsai, R. -T. Mai and Y. -H. Wu Lee (1999) Hepatitis C virus core protein interacts with cellular putative RNA helicase. J. Virol 73, 2841-2853.

L. -R. You, C. -M. Chen and Y. -H. Wu Lee. (1999) The hepatitis C virus core protein modulates the NF-kB signal pathway triggering by lymphotoxin-beta receptor ligand and tumor necrosis factor-alpha. J. Virol 73, 1672-1681.

C. -M. Chen*, L. -R. You*, L. -H. Hwang and Y. -H. Wu Lee. (1997) Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-β receptor. J. Virol 71, 9417-9426. ( * equal contribution)

R. Y. Wu, L. -R. You and T. S. Soong. (1994) Nucleotide sequences of two circular single-stranded DNAs associated with banana bunchy top virus. Phytopathology 84, 952-958.

C. G. Lin, L. -R. You and S. J. Lo. (1993) Expression and stability of the hepatitis B pol protein in Escherichia coli. J. Gestroentrology and Hepatology 8, S54-58.

S. J. Lo, L. -R. You and Y. -H. Wu Lee. (1990) The hepatitis B virus X-C fusion protein is unlikely to be produced by the mechanism of ribosomal frameshifting. Virology 178, 584-587.