佟超,女,浙江大學生命科學研究院教授、研究員、博士生導師。美國德克薩斯大學西南醫學中心(UTSW)遺傳及發育生物學博士,美國貝勒醫學院( Baylor College of Medicine) 人類分子遺傳學系博士後。
2017年4月,入選教育部2016年度“長江學者獎勵計畫”青年學者。
基本介紹
- 中文名:佟超
- 國籍:中國
- 職業:教授
- 主要成就:長江學者
- 性別:女
人物經歷,所獲獎勵,人物成就,研究方向,發表論文,
人物經歷
教育和工作背景:1995-1999:南開大學 生化及分子生物學系 學士
1999-2002: 中國科學院動物研究所 生殖生物學 碩士
2002-2006: 美國德克薩斯大學西南醫學中心(UTSW)遺傳及發育生物學 博士
2007-2011: 美國貝勒醫學院( Baylor College of Medicine) 人類分子遺傳學系 博士後
2011-至今: 浙江大學生命科學研究院教授,研究員,博士生導師
所獲獎勵
2000:中國科學院董事東方獎學金
2002:中國科學院院長獎學金優秀獎
2007:Developmental biology training grant
2008: “Brain disorders and Development” training grant
2004-至今:member of Genetics society of America
人物成就
2017年4月,入選教育部2016年度“長江學者獎勵計畫”青年學者。
研究方向
我們研究組致力於研究神經系統發育及神經退行性疾病的分子機制。我們主要感興趣的問題是神經細胞軸突如何找到其靶細胞並與之建立精確突觸連線,以及細胞自噬通路如何維持神經細胞完整性防止神經退行性疾病的發生。我們的目標是通過果蠅遺傳篩選的方法尋找參與神經軸突定位及神經細胞完整性維持的新基因,闡明其作用的分子機理, 並最終在高等動物中檢驗此作用機制的保守性。從而為臨床實踐提供理論依據。同時,我們也希望我們的研究能夠拓展人們對細胞之間相互作用以及細胞自噬等基本細胞生物學過程的了解,為攻克人類疾病做出貢獻。
神經元軸突定位
在大腦發育過程中,10億個神經元整合多種信號相互連線形成約1兆個神經突觸。神經元軸突尋找其靶細胞並與之建立精確突觸連線對於神經系統的發育和神經迴路的建立至關重要。而人們對於神經元如何整合外界信號從而精密調節其軸突行為的了解還非常有限。近年研究表明,不正常的軸突定向及突觸連線可以導致多種神經系統先天疾病,例如智障,自閉症,以及神經退行性疾病。因此,研究神經元軸突定向及突觸連線建立的分子機理仍是當今神經生物學的重要任務之一。果蠅的視覺神經系統因其結構的模組性,進化上的保守性,以及實驗上的可操作性為我們解析神經元軸突定向及突觸連線建立的分子機理提供了一個極好的模型。我們在前期工作中,通過大規模遺傳篩選發現一個進化上保守的新基因rich調節感光神經細胞R7的軸突定向。Rich蛋白與Rab6結合併正向調節Rab6的活性, 進而影響細胞表面粘聯蛋白N-Cadherin 的分布,造成R7軸突定位異常。我們將進一步研究N-Cadherin 在細胞中的運輸方式,繼續研究Rich 如何調節Rab6活性, 並進而研究Rich 哺乳動物同源基因的功能。
細胞自噬與神經退行性疾病
隨著人類壽命的增長,神經退行性疾病的發生日益普遍,嚴重影響人類生活質量。然而,人們對神經退行性疾病發生髮展的分子機理還知之甚少。神經元細胞壽命很長,又不能通過細胞分裂稀釋細胞中異常的蛋白和損壞的細胞器。因此識別並清除這些廢物,防止他們的堆積造成的細胞毒性對神經細胞來講十分重要。近年研究表明,細胞自噬功能異常在神經退行性疾病中相當普遍。並且,在小鼠和果蠅中敲除細胞自噬相關基因,均可誘導神經退行性疾病類似症狀。重要的是,人們發現調節細胞自噬功能可以減緩多種神經退行性疾病症狀。因此研究細胞自噬這一生物過程,尋找新的調節細胞自噬的基因,對我們闡明神經退行性疾病的分子機理,探索新的治療方案都至關重要。
我們在前期工作中通過大規模遺傳篩選,發現多個果蠅突變株具有細胞自噬障礙。其中一些基因的突變在人類中導致神經退行性疾病,但其功能從未與細胞自噬連繫起來。對這些基因的研究將為我們闡明這些神經退行性疾病的致病機理提出治療方案提供幫助。此外,我們還發現同是編碼線粒體蛋白的基因, 有些基因的突變會促進細胞自噬,而另外一些的突變卻抑制細胞自噬。 因為線粒體是通過細胞自噬進行清除的,對這些基因的進一步的研究將有助於我們了解細胞自噬的信號傳導和底物識別將有很大幫助。此外在我們已經篩出的基因中還有參與細胞中重要信號通路的分子,參與細胞內膜泡運輸的分子,以及未知功能的新基因。進一步研究這些分子在細胞自噬中的作用將為我們全面了解這一重要生物過程開啟新的一頁。
發表論文
1.Tong, C., Ohyama, T., Tie, A., Rajan, A., Haueter, C., Bellen, HJ. Rich regulates target specificity of photoreceptor cells and N-Cadherin trafficking in the Drosophila visual system via Rab6. Neuron Accepted
2. Jia, H., Liu, Y., Xia, R.,Tong, C., Yue, T., Jiang, J., Jia, J. (2010). Casein kinase 2 promotes hedgehog signaling by regulating both smoothened and cubitus interruptus. J Biol Chem. 285(48):37218-26.
3. Chen, Y., Li, S.,Tong, C., Zhao, Y., Wang, B., Liu, Y., Jia, J., Jiang, J. (2010). G protein-coupled receptor kinase 2 promotes high-level Hedgehog signaling by regulating the active state of Smo through kinasedependent and kinase-independent mechanisms in Drosophila. Genes Dev. 24(18):2054-67.
4. Bellen, HJ.,Tong, C., Tsuda, H. (2010). 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nat Rev Neurosci. 11(7), 514-522
5. Tsuda, H., Han, SM., Yang, Y.,Tong, C., Lin, YQ., Mohan, K., Haueter, C., Zoghbi, A., Harati, Y., Kwan, J., Miller, MA., Bellen HJ. (2008). The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell. 133(6), 963-77.
6. Zhao, Y.,Tong, C., Jiang, J. (2007). Transducing the Hedgehog signal across the plasma membrane. Fly.1(6), 333-6.
7.Tong, C., Jiang, J. (2007). Using immunoprecipitation to study protein-protein interactions in the hedgehogsignaling pathway. Methods Mol Biol. 397, 215-30.
8. Zhao, Y.*,Tong, C*., Jiang, J. (2007). Hedgehog regulates smoothened activity by inducing a conformational switch. Nature 450, 252-8. (*共同第一作者)
9. Jia, J., Zhang, L., Zhang, Q.,Tong, C., Wang, B., Hou, F., Amanai, K., and Jiang, J. (2005).Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus interruptus for Slimb/beta-TRCPmediated proteolytic processing. Developmental Cell 9, 819-830.
10. Zhang, W., Zhao, Y.,Tong, C., Wang, G., Wang, B., Jia, J., and Jiang, J. (2005). Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus. Developmental Cell 8, 267-278.
11. Jia, J.*,Tong, C.*, Wang, B., Luo, L., and Jiang, J. (2004). Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I. Nature 432, 1045-1050. (* 共同第一作者)
12. Jia, J.,Tong, C., and Jiang, J. (2003). Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail. Genes and Development 17, 2709-2720.
13. Moskalenko, S.,Tong, C., Rosse, C., Mirey, G., Formstecher, E., Daviet, L., Camonis, J., and White, M. A. (2003). Ral GTPases regulate exocyst assembly through dual subunit interactions. The Journal of biological chemistry 278, 51743-51748.
14.Tong, C., Fan, H. Y., Chen D, Y., Song, X. F., Schatten, H., and Sun, Q. Y. (2003). Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: microtuble organization, asymmetric division and metaphase II arrest. Cell Research 13, 375-383.
15. Fan, H. Y.,Tong, C., Teng, C. B., Lian, L., Li, S. W., Yang, Z. M., Chen, D. Y., Schatten, H., and Sun, Q.Y. (2003). Characterization of Polo-like kinase-1 in rat oocytes and early embryos implies its functional roles in the regulation of meiotic maturation, fertilization, and cleavage. Molecular Reproduction and Development 65, 318-329.
16. Fan, H. Y.,Tong, C., Lian, L., Li, S. W., Gao, W. X., Cheng, Y., Chen, D. Y., Schatten, H., and Sun, Q. Y. (2003). Characterization of ribosomal S6 protein kinase p90rsk during meiotic maturation and fertilization in pig oocytes: mitogen-activated protein kinase-associated activation and localization. Biology of Reproduction 68, 968-977.
17. Cheng, Y., Fan, H. Y., Wen, D. C.,Tong, C., Zhu, Z. Y., Lei, L., Sun, Q. Y., and Chen, D. Y. (2003). Asynchronous cytoplast and karyoplast transplantation reveals that the cytoplasm determines the developmental fate of the nucleus in mouse oocytes. Molecular Reproduction and Development 65, 278-282.
18. Yao, L. J., Fan, H. Y.,Tong, C., Chen, D. Y., Schatten, H., and Sun, Q. Y. (2003). Polo-like kinase-1 in porcine oocyte meiotic maturation, fertilization and early embryonic mitosis. Cellular and molecular biology (Noisy-le-Grand, France) 49, 399-405.
19. Fan, H. Y., Li, M. Y.,Tong, C., Chen, D. Y., Xia, G. L., Song, X. F., Schatten, H., and Sun, Q. Y. (2002). Inhibitory effects of cAMP and protein kinase C on meiotic maturation and MAP kinase phosphorylation in porcine oocytes. Molecular Reproduction and Development 63, 480-487.
20. Fan, H. Y.,Tong, C., Li, M. Y., Lian, L., Chen, D. Y., Schatten, H., and Sun, Q. Y. (2002). Translocation of the classic protein kinase C isoforms in porcine oocytes: implications of protein kinase C involvement in the regulation of nuclear activity and cortical granule exocytosis. Experimental Cell Research 277, 183-191.
21.Tong, C., Fan, H. Y., Lian, L., Li, S. W., Chen, D. Y., Schatten, H., and Sun, Q. Y. (2002). Polo-like kinase-1 is a pivotal regulator of microtubule assembly during mouse oocyte meiotic maturation, fertilization, and early embryonic mitosis. Biology of Reproduction 67, 546-554.
22.Jia, J.*,Tong, C.*, Wang, B., Luo, L., and Jiang, J. (2004). Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I.Nature432, 1045-1050. (*共同第一作者)
23.Jia, J.,Tong, C.,and Jiang, J. (2003). Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail.Genes and Development17, 2709-2720.
24.Moskalenko, S.,Tong, C., Rosse, C., Mirey, G., Formstecher, E., Daviet, L., Camonis, J., and White, M. A. (2003). Ral GTPases regulate exocyst assembly through dual subunit interactions.The Journal of biological chemistry278, 51743-51748.
25.Fan HY,Tong C, Teng CB, Lian L, Li SW, Yang ZM, Chen DY, Schatten H, Sun QY. Characterization of Polo-like kinase-1 in rat oocytes and early embryos implies it’s functional roles in the regulation of meiotic maturation and cleavage.Molecular Reproduction and Development,200365:318-329.
26.Fan HY,Tong C, Lian L, Li SW, Gao WX, Cheng Y, Chen DY, Schatten H, Sun QY. Characterization of ribosomal S6 protein kinase p90rsk during meiotic maturation and fertilization in pig oocytes: MAPK-associated activation and localization.Biology of Reproduction, 2003,68:968-977.
27.Tong C, Fan HY, Lian L, Li SW, Chen DY, Schatten H, Sun QY. Polo-like kinase 1 is a pivotal regulator of micrutubule assembly during mouse oocyte meiotic maturation, fertilization, and early embryonic mitosis.Biology of Reproduction, 2002, 67:546-554.
28.Fan HY, Li MY,Tong C, Chen DY, Xia GL, Song XF, Schatten H, Sun QY. Inhibitory effects of cAMP and protein kinase C on meiotic maturation and MAP kinase phosphorylation in porcine oocytes.Molecular Reproduction and Development, 2002, 63: 480-487.
29.Fan HY,Tong C, Li MY, Lian L, Chen DY, Schatten H, Sun QY. Translocation of classical protein kinase C (cPKC) isoforms in porcine oocytes: implications of PKC involvement in the regulation of nuclear activity and cortical granule exocytosis.Experimental Cell Research, 2002, 277:183-191.
30.Tong C, Fan HY, Li SW, Chen DY, Schatten H, Song XF, Sun QY. Effects of MEK inhibitor U0126 on meiotic progression in mouse oocyte: microtuble organization, asymmetric division and metaphase II arrest.Cell Research, 2003, 13:375-383.
31.Cheng Y, Fan HY, Wen DC,Tong C,Zhu ZY, Lei L, Sun QY, Chen DY. Asynchronous cytoplast and karyoplast transplantation reveals that the cytoplasm determines the developmental fate of the nucleus in mouse oocytes.Molecular Reproduction and Development, 200365:278-282.
32.Yao LJ, Fan HY,Tong C,Chen DY, Sun QY. Polo-like kinase-1 in porcine oocyte meiotic maturation, fertilization and early embryonic mitosis.Cellular and Molecular Biology, 2003, 49(3):399-405.
33.Fan HY,Tong C, Chen DY, Sun QY. Roles of MAP kinase signaling pathway in meiosis of oocytes.Chinese Science Bulletin, 47:1157-1162.
34.Fan HY,Tong C, Chen DY, Sun QY. Roles of protein kinase C in meiotic maturation and fertilization of oocytes.Progress in Natural Science, 2003, 13:401-406.
35.Li MY, Fan HY,Tong C,Chen DY, Xia GL, Sun QY. Mitogen-activated protein kinase regulates cell cycle progression in pig oocytes and fertilized eggs.Chinese Science bulletin, 2002, 47: 843-847.