蔡欣祐

蔡欣祐 Ph.D. Hsin-Yue Tsai

專任副教授 Associate Professor

研究領域:
核糖核酸生化學,次世代定序結果分析,線蟲發展生物學
RNA biochemistry, Next Generational Sequencing data analysis

研 究 室:
基礎醫學大樓1523室
Basic Medicine Building 1523

Tel:886-2-23123456 ext. 288588 (office) or 288589 (lab)

 

我們實驗室主要在瞭解和探討核糖核酸(RNA)參與各式細胞分化的機制,及挖掘新的RNA調控的途徑。而其中我們尤其著眼於MCPIP (又名Regnase-1), 一個降解RNA的酵素,所參與的細胞分化機制。我們主要使用線蟲,巨噬細胞及內皮細胞做我們研究的對象,用生化,分生及遺傳的技術(如 CRISPR, 次世代定序…)來了解MCPIP及其同源蛋白如何調控RNA的降解,進而影響細胞的分化。目前實驗室的四大方向為:

  1. MCPIP 如何調控癌細胞相關之巨噬細胞(tumor associated macrophage)的轉變
    癌細胞相關之巨噬細胞是被癌細胞馴化的巨噬細胞,扮演著幫助癌細胞擴散的功能。先前的文獻中已證實MCPIP尤其是降解RNA的能力,在巨噬細胞被馴化的過程中扮演著重要的角色。我們正在發展 CRISPR interference screening 的平台,來發掘其參與的路徑,及其與粒線體功能的關係。
  2. MCPIP 如何參與血管新生(Angiogenesis)的機制
    血管新生(Angiogenesis)是癌細胞獲得養分的主要方法,先前的文獻中指出MCPIP蛋白質是影響血管新生的重要關鍵。
  3. MCPIP在線蟲的同源蛋白之一如何影響線蟲精子的功能
    在用CRISPR 建立不同的基因變異中,我們發現其中一個MCPIP的同源蛋白會因為影響了特定族群與Argonaute結合的小RNA而造成線蟲的精子失去功能,我們利用全基因篩選找到幾個基因可以使精子重新回復功能,也正在了解這些基因如何造成精子功能的恢復。
  4. MCPIP 在線蟲的另一同源蛋白(REGE-1)如何影響線蟲的免疫反應
    線蟲中最相似於MCPIP的同源蛋白為 REGE-1, 然而,線蟲並無已知的MCPIP的受質,細胞激素。這個高度同源的REGE-1如何參與線蟲的免疫機制,我們將會從REGE-1調控的RNA去探討。

 

Our lab is interested in the mechanistic aspect of how RNA involves in various cell differentiation pathways, for instance macrophage polarization, angiogenesis stimulation, etc. and exploring new RNA players in these pathways. We also focus our search specifically on RNAs that are regulated by a ribonuclease named MCPIP1. The ribonuclease function of MCPIP1 (also named Regenase-1) is known critical for various cancer related processes including tumor associated macrophage polarization, angiogenesis in mammalian cells. We use C. elegans, bone marrow derived macrophage, and endothelium cell lines as our model system to exploring how MCPIP and its homolog promoting cell differentiation. The projects in our lab including:

  1. How MCPIP promotes tumor associated macrophage polarization.
  2. How MCPIP promotes angiogenesis in endothelium cell
  3. Why MCPIP C. elegans homolog protein is essential for spermatogenesis at elevated temperature
  4. How the MCPIP C. elegans homolog protein, REGE-1, participates in C. elegans immunity. 

2000­‐2006 Ph.D. (MCDB), The Ohio State University

1999­‐2000* MS (Biochemistry), The Ohio State University
* Transferred to the PhD program

1994-­‐1998 B.S.(Zoology)(動物系), National Taiwan University

08/2015 – to date
Assistant Professor
Institute of Molecular Medicine
National Taiwan University, College of Medicine
Taipei, Taiwan

07/2013 – 07/2015
Postdoctoral Research Fellow
Advisor:Dr. Ming-Daw Tsai(蔡明道)
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

10/2006–07/2013
Postdoctoral Research Fellow
Advisor: Dr. Craig C. Mello
University of Massachusetts Medical school
Program in Molecular Medicine, Worcester, MA

03/2006–09/2006
Postdoctoral Research Fellow
Advisor: Dr. Venkat Gopalan
Department of Biochemistry, The Ohio State University, Columbus, OH 

09/1999–03/2006
Graduate Teaching/Research Assistant or Research Fellow
Advisor: Dr. Venkat Gopalan
Department of Biochemistry, The Ohio State University, Columbus, OH
 

 

PhD students:
蔡伊婷
曾依婷
馬佳宏

 

Master students:
陳威羽
吳文婷
 

Former students:
張筳婕
沈秋媛
吳以新
何冠霖
林恬伊

 

 

 

Tsai YT, Chang CH, #Tsai HY (2023) Rege-1 promotes C. elegans survival by modulating IIS and TOR pathways. PLOS Genetics. In press

#Tsai HY, Cheng HT, Tsai YT (2022) Biogenesis of C. elegans spermatogenesis small RNAs is initiated by a zc3h12a-like ribonuclease. Sci Adv. 8(32):eabm0699.

Lin, C.C., Shen YR, Chang CC, Guo XY, Young, YY, Lai TY, Yu IS, Lee CY, Chuang TH, Tsai HY, #Hsu LC (2021) Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation. Nat Commun 12(1):3878.

Lee HC, Fu CY, Lin CY, Hu JR, Huang TY, Lo KY, Tsai HY, Sheu JC, #Tsai HJ (2021) Poly(U)-specific endoribonuclease ENDOU promotes translation of human CHOP mRNA by releasing uORF element-mediated inhibition. EMBO J. 40(11):e104123.

Liu, M.S., Tsai, H.Y., Liu, X.X., Ho, M.C., Wu, W.J., and #Tsai, M.D. (2016) Structural Mechanism for the fidelity Modulation of DNA Polymerase L. J. Am. Chem. Soc. Feb 11.

Tsai, H.Y., Chen, C.C., Conte, D. Jr, Moresco, J.J., Chaves, D.A., Mitani, S., Yates, J.R. 3rd, Tsai, M.D., and Mello, C.C. A ribonuclease coordinates siRNA amplification and mRNA cleavage during RNAi. Cell. 2015 Jan 29;160(3):407-19.

Wen-An Pan, Hsin-Yue Tsai, Shun-Chang Wang, Michael Hsiao, Pei-Yu Wu*, and Ming-Daw Tsai.* The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression. RNA Biology. 2015;12(3):255-67.

Chen, W.Y., Pulukkunat, D.K., Cho, I.M., Tsai, H.Y., Gopalan, V. (2010) Dissecting functional cooperation among protein subunits in archaeal RNase P, a catalytic ribonucleoprotein complex. NUCLEIC ACIDS RESEARCH. 2010 Aug; 38, 8316-8327.

Tsai, H.Y., Pulukkunat, D.K., Woznick, W.K. and Gopalan, V. (2006) Functional reconstitution and characterization of Pyrococcus furiosus RNase P. Proc. Natl. Acad. Sci. 103, 16147-16152.

Boomershine, W.P., McElroy, C.A., Tsai, H.Y., Wilson, R.C., Gopalan, V., and Foster, M.P. (2003) Structure of Mth11/Mth Rpp29, an essential protein subunit of archaeal and eukaryotic RNase P. Proc. Natl. Acad. Sci. 100, 15398-15403.

Tsai, H.Y., Masquida, B., Biswas, R., Westhof, E. and Gopalan, V. (2003) Molecular modeling of the three-dimensional structure of the bacterial RNase P holoenzyme. J Mol. Biol., 325, 661-675.

Tsai, H.Y., Lai, L.B. and Gopalan, V. (2002) A modified pBluescript-based vector for facile cloning and transcription of RNAs. Anal. Biochem. 303, 214-217.

* First author
# Corresponding author