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皮海薇

皮海薇 (Haiwei Pi)


實驗室資料

職稱:副教授 研究室:發育及幹細胞生物學研究室
最高學歷:博士 學校/國家:State University of New York at Stony Brook/ USA
分機號碼:3361 電子郵件帳號:haiwei@mail.cgu.edu.tw

研究室現有:
博士後研究員 1 人
博士班研究生 2 人
碩士班研究生 1 人
專任研究助理 3 人
大學部專題生 5 人

個人網頁: http://haiwei.tw

Research interest:

      My laboratory is interested in studying how cells decide to differentiate into specialized cells with distinct functions. This process, call cell fate determination, is critical for embryonic development and adult tissue homeostasis. We study cell fate determination in the context of whole animal, the powerful genetic model organism fruit fly Drosophila melanogaster, combined with molecular, cellular and confocal microscopic approaches.

      There are two major topics in the lab: (1) the roles of nuclear actin in differentiation of sensory organ precursors (SOPs), the neural precursors of Drosophila peripheral sensory organs. Actin, the major components of cytoskeleton, has recently been demonstrated to play important roles in several basic nuclear processes such as RNA polymerase-mediated transcription, chromatin remodeling, and RNA processing. By combining biochemical and molecular analyses in culture cells as well as genetic and functional analysis in Drosophila, we show that nuclear actin is required for neural precursor differentiation by acting as transcriptional co-factor of bHLH neurogeneic proteins Achaetae and Scute. In the future, we would like to study how the specific association between nuclear actin and Achaetae/Scute is achieved, and how nuclear actin levels might be regulated during neurogenesis and development.

      The second topic in the lab is to study the roles of protein degradation and cell signaling in self-renewal and differentiation of male germline stem cells (GSCs), the adult stem cells that produce gametes throughout the reproductive life of male animals. Our study has shown that BMP signaling, the key regulators of GSC self-renewal, is downregulated as male gonads develop. The downregulation is mediated by the ubiquitin E3 ligase Smurf to control the numbers of GSCs as well as the transit-amplifying cells, the differentiating daughter cells of the GSCs. In the future, we will focus on the regulation of GSC self-renewal and differentiation as well as BMP signaling in GSCs by the stem cell microenvironment.

      我們實驗室主要研究細胞命運決定的過程。在發育過程中,胚胎細胞藉由命運決定及接下來的分化過程來形成各式功能的細胞。命運決定及分化作用也會在成體中發生,並對成體組織代謝及恆定極為重要。因此,研究細胞命運決定及分化不只有助於了解及治療因細胞功能不足而產生的先天性疾病,且直接有助於未來在醫學上產生新生細胞來修補受損組織。

      我們主要用果蠅這個模式生物來研究在活體中,基因如何調控細胞細胞命運決定及分化。實驗室中有兩個主要方向:(1)探討神經母細胞的形成過程中,原神經蛋白如何活化下游基因來促進母細胞分化。我們目前著重於探討核內肌動蛋白和原神經蛋白之間的關係。(2)成體幹細胞 (adult stem cell) 自我新生的調控在 維持組織恆定中扮演 重要功能 。自我新生能力太強時, 細胞分化會被抑制。 反之, 過早進入細胞分化會降低幹細胞的自我新生。我們實驗室最近的研究在探討成體中的配子幹細胞如何受到BMP 或其它訊息傳導路徑的影響來維持在自我新生及細胞分化中的協調。


(A) 果蠅的翅膀
(B) 感覺神經剛毛(箭頭)位於果蠅前翅脈邊緣,負責感覺外界機械性刺激
(C) 果蠅成體testis前端,圍繞在hub(中心白色細胞)周圍的細胞為成體配子幹細胞(箭頭)


近五年計劃:

行政院國家科學委員會:
2008/8/1~2011/7/31 Phyllopod調節蛋白質降解作用在果蠅神經發育的功能
2011/8/1~2012/7/31 COP9複雜亞單位與核內肌動蛋白對果蠅感覺器官的分布及命運決定之影響
2012/8/1~2015/7/31 探討COP9複雜亞單位對於果蠅蛻皮激素訊息傳遞鏈的抑制機轉

長庚醫院:
2009/12/1~2012/11/30 在果蠅精子幹細胞及子細胞發育中,TGF-β訊息傳遞的副調控和Notch訊息路徑的功能
2013/1/1~2015/12/31 老化果蠅雄性生質幹細胞系統中,smurf扮演抑制細胞過度增生的角色


實驗室近年榮譽:

學年度 姓名 獲獎項目
100 蕭韻凌
(博士班)
生物醫學所論文壁報競賽,榮獲博士班優勝
100 謝昌哲
(碩士班)
生物醫學所論文壁報競賽,榮獲碩士班第三名
100 黃意霖
(大學部)
中央研究院神經科學暑期研究獎學金
100 廖唯甯
(大學部)
中央研究院神經科學暑期研究獎學金
101 蕭韻凌
(博士班)
2012年神經科學學術年會壁報展,榮獲第一名
101 黃亦君
(博士班)
2013年Asia-Pacific Drosophila Research Conference (韓國漢城)獲得傑出壁報獎
102 黃亦君
(博士班)
第22屆細胞及分子生物新知研討會獲得傑出壁報獎

近五年研究著作:

  1. Kao SH, Tseng CYWan CLSu YHHsieh CCPi HHsu HJ*. (2014) Aging and insulin signaling differentially control normal and tumorous germline stem cells. Aging Cell doi:10.1111/acel.12288.

  2. Huang YC, Lu YN, Wu JT, Chien CT*, Pi H*. (2014) The COP9 Signalosome Converts Temporal Hormone Signaling to Spatia Restriction on Neural Competence. PLoS Genetics 10(11):1004760.

  3. Hsiao YL, Chen YJ, Chang YJ, Yeh HF, Huang YC and Pi H*. (2014) Proneural proteins Achaete and Scute associate with nuclear actin to promote external sensory organ formation. Journal of Cell Science 127:182-90.

  4. Chang YJ†, Pi H†*, Hsieh CC, Fuller MT. (2013) Smurf-mediated differential proteolysis generates dynamic BMP signaling in germline stem cells during Drosophila testis development. Developmental Biology 383(1):106-20. (†These two authors contributed equally to this work).

  5. Yang WK, Peng YH, Li H, Lin HC, Lin YC, Lai TT, Suo H, Wang CH, Lin WH, Ou CY, Zhou X, Pi H, Chang HC, Chien CT.* (2011) Nak regulates localization of clathrin sites in higher-order dendrites to promote local dendrite growth. Neuron 72, 285-299.

  6. Pi H†*, Huang YC†, Chen C, Lin CD, Yeh HF, Pai LM. (2011) Identification of 11-amino acid peptides that disrupt Notch-mediated processes in Drosophila. Journal of Biomedical Science 18, 42. (†These two authors contributed equally to this work).

  7. Wu JT, Lin WH, Chen WY, Huang YC, Tang CY, Ho MS., Pi H, Chien CT*. (2011) CSN-mediated deneddylation differentially modulates Ci155 proteolysis to promote Hedgehog signalling responses. Nature Communications 2,182.

  8. Pi H, Lee LW, Lo SJ*. (2009) New Insights into Polycistronic Transcripts in Eukaryotes. Chang Gung Med J. 32, 494-8.

  9. Chang PJ, Hsiao YL, Tien AC, Li YJ, Pi H*. (2008) Negative feedback regulation of proneural proteins controls the timing of neural precursor division. Development 135, 3021-30. (Recommended by Dr. Patricia Simpson in  Faculty of 1000).

  10. Ho MS, Ou CY, Chan Y, Chien CT.*, Pi H*. (2008) The utility F-box for protein destruction. Cellular and Molecular Life Science 65, 1977-2000.

  11. Pi H and Chien CT.* (2007) Getting the edge: neural precursor selection. Journal of Biomedical Science 14, 467-473.

  12. Pi H, Huang SK, Tang CY, Sun H, Chien CT*. (2004) phyllopod is a target gene  of proneural protein in Drosophila external sensory organ development. PNAS. 101, 8378-83.

  13. Chang CW, Pi H, Chien CT, Hsu CP*. (2003) Network modeling of Drosophila external sensory organ precursor formation: The role of recently studied genes. Journal of Genetics and Molecular Biology. (Taiwan) 14, 243-251

  14. Ou CY, Pi H, Chien CT*. (2003) Control of protein degradation by E3 ubiquitin ligases in Drosophila eye development. Trends in Genetics 19, 353-414.

  15. Pi H, Wu HJ, Chien CT*. (2001) A dual function of phyllopod in Drosophila external sensory organ development: cell fate specification of sensory organ precursor and its progeny. Development 128, 2699-2710.

  16. Pi H, Chien CT, Fields S*. (1997) Transcriptional activation upon pheromone stimulation mediated by a small domain of Saccharomyces cerevisiae Ste12p. Molecular and Cellular Biology 17, 6410-6418.

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